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Raj M, Meena A, Seth R, Mathur A, Luqman S. An update on nanoformulations with FDA approved drugs for female reproductive cancer. J Microencapsul 2025; 42:266-299. [PMID: 40114400 DOI: 10.1080/02652048.2025.2474457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 02/26/2025] [Indexed: 03/22/2025]
Abstract
Female reproductive cancers, including ovarian, cervical, breast, gestational trophoblastic and endometrial cancer, present significant challenges in therapy and patient prognosis. Conventional chemotherapy often lacks selectivity, leading to systemic toxicity and reduced treatment efficacy. Nanotechnology has emerged as a promising approach to improve drug delivery and therapeutic outcomes. Encapsulation of FDA-approved drugs within nanocarriers such as liposomes, polymeric nanoparticles, and lipid nanoparticles enables controlled drug release, reduces off-target effects, and enhances drug accumulation at tumor sites. This targeted delivery minimizes damage to healthy tissues and improves patient survival rates. Additionally, nanoformulations facilitate combination therapy, overcoming drug resistance and maximizing therapeutic efficacy. Despite promising results, challenges like scalability, reproducibility, and regulatory approvals hinder widespread clinical applications. Developing personalized nanoformulations tailored to individual patient profiles offers potential for precision cancer therapy. This study explores the role of nanoformulations in enhancing the therapeutic potential of FDA-approved drugs for treating female reproductive cancers.
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Affiliation(s)
- Mahima Raj
- Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, India
| | - Abha Meena
- Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Richa Seth
- Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Anurag Mathur
- Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Suaib Luqman
- Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
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2
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Jiang Y, Cao Y, Yao Y, Zhang D, Wang Y. Chitosan and hyaluronic acid in breast cancer treatment: Anticancer efficacy and nanoparticle and hydrogel development. Int J Biol Macromol 2025; 301:140144. [PMID: 39848359 DOI: 10.1016/j.ijbiomac.2025.140144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 01/09/2025] [Accepted: 01/20/2025] [Indexed: 01/25/2025]
Abstract
The pervasive global health concern of breast cancer necessitates the development of innovative therapeutic interventions to enhance efficacy and mitigate adverse effects. Chitosan and hyaluronic acid, recognized for their biocompatibility and biodegradability, present compelling options for the novel drug delivery systems and therapeutic platforms in the context of breast cancer management. This review will delineate the distinctive attributes of chitosan and hyaluronic acid, encompassing their inherent anticancer properties, targeting capabilities, and suitability for chemical modifications along with nanoparticle development. These characteristics render them exceptionally well-suited for the fabrication of nanoparticles and hydrogels. The intrinsic anticancer potential of chitosan, in conjunction with its mucoadhesive properties, and the robust binding affinity of hyaluronic acid to CD44 receptors, facilitate specific drug delivery to the malignant cells, thus circumventing the limitations inherent in traditional treatment modalities such as chemotherapy. The incorporation of these materials into nanocarriers allows for the co-delivery of therapeutic agents, thereby potentiating synergistic effects, while hydrogel systems provide localized, controlled drug release and facilitate tissue regeneration. An analysis of advancements in their synthesis, functionalization, and application is presented, while also acknowledging challenges pertaining to scalability and clinical translation.
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Affiliation(s)
- Yanlin Jiang
- Department of Breast and Thyroid Surgery, the Affiliated Zhongshan Hospital of Dalian University, China
| | - Yu Cao
- Department of Surgical Oncology and Breast Surgery, The First Hospital of China Medical University, Shenyang 110001, China
| | - Yiqun Yao
- Department of Breast and Thyroid Surgery, the Affiliated Zhongshan Hospital of Dalian University, China
| | - Dianlong Zhang
- Department of Breast and Thyroid Surgery, the Affiliated Zhongshan Hospital of Dalian University, China.
| | - Yuying Wang
- Department of Breast Surgery, The Cancer Hospital of China Medical University Liaoning Cancer Hospital & Institute, China.
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3
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Verma M, Yadav K, Parihar R, Dutta D, Chaudhuri S, Sivakumar S. Active tumor targeting by core-shell PDMS-HA nanoparticles with sequential delivery of doxorubicin and quercetin to overcome P-glycoprotein efflux pump. NANOSCALE 2025; 17:5033-5055. [PMID: 40013710 DOI: 10.1039/d4nr03040k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/28/2025]
Abstract
The therapeutic efficacy of chemotherapy in various malignancies and solid tumors is significantly limited when used as monotherapy. This study explored a combined treatment approach for breast cancer cells involving sequential delivery of doxorubicin followed by quercetin, both delivered via polydimethylsiloxane nanoparticles decorated with hyaluronic acid. Quercetin inhibits P-glycoprotein efflux action to enhance doxorubicin activity by increasing its intracellular accumulation; hence, both synergistically suppress cancer cell growth by promoting cytotoxicity and apoptosis. Quercetin reverses multidrug resistance, induces arrest in the cell cycle, and alters the mitochondrial membrane potential. The successful delivery and internalization of these drugs into breast cancer cells were confirmed through CD44 ligand recognition, inhibiting cell viability via apoptosis (caspase-induced) and cell arrest in the G2/M phase of the cell cycle. Furthermore, in an MCF-7 (breast cancer) cell-derived xenograft tumor model using NOD/SCID mice, the core-shell PDMS-HA nanoparticle system carrying quercetin and doxorubicin resulted in approximately 65% tumor volume reduction, outperforming the loaded single drug and free drug combination. These results were supported by the TUNEL assay and proliferation index by Ki-67 immunohistochemistry staining, which show substantial cell death and tissue necrosis in the tumor sections. Histological studies of tumor tissues confirm enhanced anticancer efficacy with negligible systemic toxicity to normal organs. Overall, the PDMS-HA delivery system efficiently transports quercetin and doxorubicin to tumor cells, enhancing the antitumor effects against the MCF-7 tumor xenograft model in mice without adverse effects. This study suggests that the targeted co-delivery of phytochemicals and anti-cancer agents can synergistically overcome many barriers associated with tumor treatment.
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Affiliation(s)
- Madhu Verma
- Department of Chemical Engineering, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh, India.
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, India.
| | - Krishna Yadav
- Central Experimental Animal Facility, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh, India
| | - Rashmi Parihar
- Central Experimental Animal Facility, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh, India
| | - Debjani Dutta
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, India.
| | - Surabhi Chaudhuri
- Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, India.
| | - Sri Sivakumar
- Department of Chemical Engineering, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh, India.
- Material Science Programme, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh, India
- Centre for Environmental Science and Engineering, Center for Nanosciences, Mehta Family Centre for Engineering in Medicine, Gangwal School of Medical Sciences and Technology Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh, India
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Chen W, Huang J, Guo Y, Wang X, Lin Z, Wei R, Chen J, Wu X. Nanocrystals for Intravenous Drug Delivery: Composition Development, Preparation Methods and Applications in Oncology. AAPS PharmSciTech 2025; 26:66. [PMID: 39979757 DOI: 10.1208/s12249-025-03064-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Accepted: 02/06/2025] [Indexed: 02/22/2025] Open
Abstract
Intravenous routes of drug delivery are widely used in clinical practice due to the advantages of fast onset of action and avoidance of first-pass effect. Still, it is difficult to develop poorly water-soluble drugs for intravenous administration. In recent years, the application of nanocrystal technology has become more and more widespread, mainly involving reducing the particle size to the nanoparticle size range and improving its physicochemical properties to enhance the bioavailability of drugs. Intravenous nanocrystals (INCs) can show unique advantages in the vasculature, with their high drug loading capacity, low toxicity, and overcoming low solubility, which makes them a new solution in tumor therapy. In addition, INCs are mainly suspended in aqueous/oil phase media, which makes them easy to inject. Therefore, INCs may serve as a novel strategy to address poor water solubility, low bioavailability, and associated toxicity. This review contains the compositional development of INCs, and preparation methods, and provides some insights into their application in oncology.
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Affiliation(s)
- Wanjiao Chen
- Fujian University of Traditional Chinesemedicine, No. 1 Qiuyang Road, Fuzhou, 350122, China
| | - Jingyi Huang
- Fujian University of Traditional Chinesemedicine, No. 1 Qiuyang Road, Fuzhou, 350122, China
| | - Yankun Guo
- Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 85 Wujin Road, Hongkou District, Shanghai, 200080, China
| | - Xinyv Wang
- Shanghai Wei Er Lab, Shanghai, 201707, China
| | - Zhizhe Lin
- Shanghai Wei Er Lab, Shanghai, 201707, China
| | - Ruting Wei
- Fujian University of Traditional Chinesemedicine, No. 1 Qiuyang Road, Fuzhou, 350122, China
| | - Jianming Chen
- Fujian University of Traditional Chinesemedicine, No. 1 Qiuyang Road, Fuzhou, 350122, China.
- Shanghai Wei Er Lab, Shanghai, 201707, China.
| | - Xin Wu
- Fujian University of Traditional Chinesemedicine, No. 1 Qiuyang Road, Fuzhou, 350122, China.
- Shanghai Wei Er Lab, Shanghai, 201707, China.
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Mukherjee S, Joshi V, Reddy KP, Singh N, Das P, Datta P. Biopharmaceutical and pharmacokinetic attributes to drive nanoformulations of small molecule tyrosine kinase inhibitors. Asian J Pharm Sci 2024; 19:100980. [PMID: 39640056 PMCID: PMC11617995 DOI: 10.1016/j.ajps.2024.100980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 06/13/2024] [Accepted: 06/29/2024] [Indexed: 12/07/2024] Open
Abstract
Buoyed by the discovery of small-molecule tyrosine kinase inhibitors (smTKIs), significant impact has been made in cancer chemotherapeutics. However, some of these agents still encounter off-target toxicities and suboptimal efficacies due to their inferior biopharmaceutical and/or pharmacokinetic properties. Almost all of these molecules exhibit significant inter- and intra-patient variations in plasma concentration-time profiles. Thus, therapeutic drug monitoring, dose adjustments and precision medicine are being contemplated by clinicians. Complex formulations or nanoformulation-based drug delivery systems offer promising approaches to provide drug encapsulation or spatiotemporal control over the release, overcoming the biopharmaceutical and pharmacokinetic limitations and improving the therapeutic outcomes. In this context, the present review comprehensively tabulates and critically analyzes all the relevant properties (T1/2, solubility, pKa, therapeutic index, IC50, metabolism etc.) of the approved smTKIs. A detailed appraisal is conducted on the advancements made in complex formulations of smTKIs, with a focus on strategies to enhance their pharmacokinetic profile, tumor targeting ability, and therapeutic efficacy. Various nanocarrier platforms, have been discussed, highlighting their unique features and potential applications in cancer therapy. Nanoformulations have been shown to improve area under the curve and peak plasma concentration, and reduce dosing frequency for several smTKIs in animal models. It is inferred that extensive efforts will be made in developing complex formulations of smTKIs in near future. There, the review concludes with key recommendations for the developing of smTKIs to facilitate early clinical translation.
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Affiliation(s)
| | | | - Kolimi Prashanth Reddy
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research Kolkata, 168, Maniktala Main Road, Kolkata 700054, West Bengal, India
| | - Nidhi Singh
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research Kolkata, 168, Maniktala Main Road, Kolkata 700054, West Bengal, India
| | - Priyanka Das
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research Kolkata, 168, Maniktala Main Road, Kolkata 700054, West Bengal, India
| | - Pallab Datta
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research Kolkata, 168, Maniktala Main Road, Kolkata 700054, West Bengal, India
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Lhaglham P, Jiramonai L, Jia Y, Huang B, Huang Y, Gao X, Zhang J, Liang XJ, Zhu M. Drug nanocrystals: Surface engineering and its applications in targeted delivery. iScience 2024; 27:111185. [PMID: 39555405 PMCID: PMC11564948 DOI: 10.1016/j.isci.2024.111185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2024] Open
Abstract
Drug nanocrystals have received significant attention in drug development due to their enhanced dissolution rate and improved water solubility, making them effective in overcoming issues related to drug hydrophobicity, thereby improving drug bioavailability and treatment effectiveness. Recent advances in preparation techniques have facilitated research on drug surface properties, leading to valuable surface engineering strategies. Surface modification can stabilize drug nanocrystals, making them suitable for versatile drug delivery platforms. Functionalized ligands further enhance the potential for targeted delivery, enabling precision medicine. This review focuses on the surface engineering of drug nanocrystals, discussing various preparation methods, surface ligand design strategies, and their applications in targeted drug delivery, especially for cancer treatments. Finally, challenges and future directions are also discussed to promote the development of drug nanocrystals. The surface engineering of drug nanocrystals promises new opportunities for treating complex and chronic diseases while broadening the application of drug delivery systems.
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Affiliation(s)
- Phattalapol Lhaglham
- Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- Department of Manufacturing Pharmacy, Faculty of Pharmacy, Mahidol University, Sri-ayudhya Road, Bangkok 10400, Thailand
| | - Luksika Jiramonai
- Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yaru Jia
- Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China
- Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, College of Chemistry & Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Hebei University, Baoding 071002, China
| | - Baoying Huang
- MHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China
| | - Yuanyu Huang
- Advanced Research Institute of Multidisciplinary Science, School of Life Science, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing 100081, China
| | - Xueyun Gao
- Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, Beijing 100124, China
| | - Jinchao Zhang
- Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, College of Chemistry & Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Hebei University, Baoding 071002, China
| | - Xing-Jie Liang
- Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Mengliang Zhu
- Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China
- University of Chinese Academy of Sciences, Beijing 100049, China
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Liu L, Pan Y, Ye L, Liang C, Mou X, Dong X, Cai Y. Optical functional nanomaterials for cancer photoimmunotherapy. Coord Chem Rev 2024; 517:216006. [DOI: 10.1016/j.ccr.2024.216006] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Si Q, Bai M, Wang X, Wang T, Qin Y. Photonanozyme-Kras-ribosome combination treatment of non-small cell lung cancer after COVID-19. Front Immunol 2024; 15:1420463. [PMID: 39308869 PMCID: PMC11412844 DOI: 10.3389/fimmu.2024.1420463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Accepted: 08/14/2024] [Indexed: 09/25/2024] Open
Abstract
With the outbreak of the coronavirus disease 2019 (COVID-19), reductions in T-cell function and exhaustion have been observed in patients post-infection of COVID-19. T cells are key mediators of anti-infection and antitumor, and their exhaustion increases the risk of compromised immune function and elevated susceptibility to cancer. Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer with high incidence and mortality. Although the survival rate after standard treatment such as surgical treatment and chemotherapy has improved, the therapeutic effect is still limited due to drug resistance, side effects, and recurrence. Recent advances in molecular biology and immunology enable the development of highly targeted therapy and immunotherapy for cancer, which has driven cancer therapies into individualized treatments and gradually entered clinicians' views for treating NSCLC. Currently, with the development of photosensitizer materials, phototherapy has been gradually applied to the treatment of NSCLC. This review provides an overview of recent advancements and limitations in different treatment strategies for NSCLC under the background of COVID-19. We discuss the latest advances in phototherapy as a promising treatment method for NSCLC. After critically examining the successes, challenges, and prospects associated with these treatment modalities, their profound prospects were portrayed.
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Affiliation(s)
- Qiaoyan Si
- School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China
- School of Biomedical Engineering, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China
- Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
| | - Mingjian Bai
- School of Biomedical Engineering, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China
| | - Xiaolong Wang
- School of Biomedical Engineering, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China
| | - Tianyu Wang
- School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China
| | - Yan Qin
- School of Biomedical Engineering, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China
- Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
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Singh N, Chakravarti R, Das A, Gupta S, Ghosh D, Datta P. A Lipophilic Salt Form to Enhance the Lipid Solubility and Certain Biopharmaceutical Properties of Lapatinib. Mol Pharm 2024; 21:3921-3935. [PMID: 38935681 DOI: 10.1021/acs.molpharmaceut.4c00283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/29/2024]
Abstract
Lapatinib (LTP) commercially available as lapatinib ditosylate (LTP-DTS) salt is the only drug approved for the treatment of HER-positive metastatic breast cancer. A low and pH-dependent solubility results in poor and variable oral bioavailability, thus driving significant interest in molecular modification and formulation strategies of the drug. Furthermore, due to very high crystallinity, LTP and LTP-DTS have low solubility in lipid excipients, making it difficult to be delivered by lipid-based carrier systems. Thus, the present work reports a new salt form of LTP with a docusate counterion to enhance the pharmaceutical properties of the drug (LTP-DOC). NMR spectra showed a downfield shift of the methylene singlet proton from 3.83 and 4.41 ppm, indicating a lowering of electron density on the adjacent nitrogen atom and confirming the formation of amine-sulfonyl salt through the specified basic nitrogen center located adjacent to the furan ring. PXRD diffractograms of LTP-DOC indicated a reduced crystallinity of the prepared salt. The dissolution, equilibrium solubility, lipid excipient solubility, partitioning coefficient, distribution coefficient, tabletability, and in vitro cytotoxicity of the lipophilic salt of LTP were investigated. The equilibrium solubility data showed that LTP-DOC possesses a pH-independent solubility profile in the pH range of 3.5 to 7.4 with a 3.14 times higher permeability coefficient than commercial ditosylate salt. Furthermore, the prepared LTP-DOC salts showed twice higher log P than the free base and 8 times higher than LTP-DTS. The prepared LTP-DOC was found to have 4- to 9-fold higher solubility in lipid excipients like Capmul MCM C8 and Maisine CC compared to the ditosylate salt. The LTP-DOC salt was tabletable and showed approximately 1.2 times lower dissolution than commercial ditosylate salt, indicating extended-release behavior. A cytotoxicity study of LTP-DOC salt showed an approximately 2.5 times lower IC50 value than the LTP-free base and 1.7 times lower than commercial ditosylate salt with an approximately 3 times higher selectivity index. The investigations strongly indicate a high translational potential of the prepared salt form in maintaining solubility-lipophilicity interplay, enhancing the drug's bioavailability, and developing lipidic formulations.
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Affiliation(s)
- Nidhi Singh
- Polymer-based Medical Devices and Complex Drug Delivery Systems Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research Kolkata, Jadavpur 700032, India
| | - Rudra Chakravarti
- Department of Natural Products, National Institute of Pharmaceutical Education and Research Kolkata, Jadavpur 700032, India
| | - Arka Das
- Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research Kolkata, Kolkata 700054, India
| | - Sreya Gupta
- Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research Kolkata, Kolkata 700054, India
| | - Dipanjan Ghosh
- Department of Natural Products, National Institute of Pharmaceutical Education and Research Kolkata, Jadavpur 700032, India
| | - Pallab Datta
- Polymer-based Medical Devices and Complex Drug Delivery Systems Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research Kolkata, Jadavpur 700032, India
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Ghadi R, Kuche K, Date T, Nallamothu B, Chaudhari D, Jain S. Unlocking apoptosis in triple negative breast cancer: Harnessing "glutamine trap" to amplify the efficacy of lapatinib-loaded mixed micelles. BIOMATERIALS ADVANCES 2024; 159:213822. [PMID: 38442461 DOI: 10.1016/j.bioadv.2024.213822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Revised: 02/19/2024] [Accepted: 02/28/2024] [Indexed: 03/07/2024]
Abstract
Certain aggressive cancers, such as triple-negative breast cancer (TNBC), heavily bank on glutamine for their proliferation and survival. In this context, TNBC functions as a "glutamine trap," extracting circulating glutamine at a rate surpassing that of any other organ. Moreover, the overexpression of Alanine, Serine, Cysteine Transporter 2 (ASCT2), a key player in glutamine uptake, further underscores the significance of targeted therapy to enhance TNBC treatment. This led to the exploration of a novel approach involving hydrophobized Pluronic-based mixed micelles achieved through the use of docosahexaenoic acid and stapled with glutamine for displaying inherent ASCT2 targeting ability-a formulation termed LPT G-MM. LPT G-MM exhibited optimal characteristics, including a size of 163.66 ± 10.34 nm, a polydispersity index of 0.237 ± 0.083, and an enhanced drug loading capacity of approximately 15 %. Transmission electron microscopy validated the spherical shape of these micelles. In vitro release studies demonstrated drug release in a sustained manner without the risk of hemolysis. Importantly, LPT G-MM displayed heightened cellular uptake, increased cytotoxicity, a lower IC50 value, elevated reactive oxygen species, induced mitochondrial membrane depolarization, and a greater apoptosis index in TNBC cell lines compared to free LPT. The pharmacokinetic profile of LPT G-MM revealed a substantial rise in half-life (t1/2) by approximately 1.48-fold and an elevation in the area under the curve [AUC(0→∞)] by approximately 1.19-fold. Moreover, there was a significant reduction in the percentage of tumor volume by approximately 7.26-fold, along with decreased serum toxicity markers compared to free LPT. In summary, LPT G-MM demonstrated promising potential in boosting payload capacities and targeting specificity in the context of TNBC treatment.
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Affiliation(s)
- Rohan Ghadi
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India
| | - Kaushik Kuche
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India
| | - Tushar Date
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India
| | - Bhargavi Nallamothu
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India
| | - Dasharath Chaudhari
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India
| | - Sanyog Jain
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India.
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11
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Li L, Wang Z, Guo H, Lin Q. Nanomaterials: a promising multimodal theranostics platform for thyroid cancer. J Mater Chem B 2023; 11:7544-7566. [PMID: 37439780 DOI: 10.1039/d3tb01175e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/14/2023]
Abstract
Thyroid cancer is the most prevalent malignant neoplasm of the cervical region and endocrine system, characterized by a discernible upward trend in incidence over recent years. Ultrasound-guided fine needle aspiration is the current standard for preoperative diagnosis of thyroid cancer, albeit with limitations and a certain degree of false-negative outcomes. Although differentiated thyroid carcinoma generally exhibits a favorable prognosis, dedifferentiation is associated with an unfavorable clinical course. Anaplastic thyroid cancer, characterized by high malignancy and aggressiveness, remains an unmet clinical need with no effective treatments available. The emergence of nanomedicine has opened new avenues for cancer theranostics. The unique features of nanomaterials, including multifunctionality, modifiability, and various detection modes, enable non-invasive and convenient thyroid cancer diagnosis through multimodal imaging. For thyroid cancer treatment, nanomaterial-based photothermal therapy or photodynamic therapy, combined with chemotherapy, radiotherapy, or gene therapy, holds promise in reducing invasiveness and prolonging patient survival or alleviating pain in individuals with anaplastic thyroid carcinoma. Furthermore, nanomaterials enable simultaneous diagnosis and treatment of thyroid cancer. This review aims to provide a comprehensive survey of the latest developments in nanomaterials for thyroid cancer diagnosis and treatment and encourage further research in developing innovative and effective theranostic approaches for thyroid cancer.
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Affiliation(s)
- Lei Li
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, 130012, P. R. China.
- Department of Endocrinology, Lequn Branch, The First Hospital of Jilin University, Changchun, 130031, China.
| | - Ze Wang
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, 130012, P. R. China.
| | - Hui Guo
- Department of Endocrinology, Lequn Branch, The First Hospital of Jilin University, Changchun, 130031, China.
| | - Quan Lin
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, 130012, P. R. China.
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Chen J, Li J, Sun X, Lu H, Liu K, Li Z, Guan J, Song H, Wei W, Ge Y, Fan Q, Bao W, Ma B, Du Z. Precision Therapy of Recurrent Breast Cancer through Targeting Different Malignant Tumor Cells with a HER2/CD44-Targeted Hydrogel Nanobot. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2023; 19:e2301043. [PMID: 37154208 DOI: 10.1002/smll.202301043] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 04/20/2023] [Indexed: 05/10/2023]
Abstract
Heterogeneity and drug resistance of tumor cells are the leading causes of incurability and poor survival for patients with recurrent breast cancer. In order to accurately deliver the biological anticancer drugs to different subtypes of malignant tumor cells for omnidirectional targeted treatment of recurrent breast cancer, a distinct design is demonstrated by embedding liposome-based nanocomplexes containing pro-apoptotic peptide and survivin siRNA drugs (LPR) into Herceptin/hyaluronic acid cross-linked nanohydrogels (Herceptin-HA) to fabricate a HER2/CD44-targeted hydrogel nanobot (named as ALPR). ALPR delivered cargoes to the cells overexpressing CD44 and HER2, followed by Herceptin-HA biodegradation, subsequently, the exposed lipid component containing DOPE fused with the endosomal membrane and released peptide and siRNA into the cytoplasm. These experiments indicated that ALPR can specifically deliver Herceptin, peptide, and siRNA drugs to HER2-positive SKBR-3, triple-negative MDA-MB-231, and HER2-negative drug-resistant MCF-7 human breast cancer cells. ALPR completely inhibited the growth of heterogeneous breast tumors via multichannel synergistic effects: disrupting mitochondria, downregulating the survivin gene, and blocking HER2 receptors on the surface of HER2-positive cells. The present design overcomes the chemical drug resistance and opens a feasible route for the combinative treatment of recurrent breast cancer, even other solid tumors, utilizing different kinds of biological drugs.
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Affiliation(s)
- Juan Chen
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China
- Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yi-Shan Road, Shanghai, 200233, China
| | - Jinjin Li
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China
| | - Xiaolu Sun
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China
| | - Huixia Lu
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China
| | - Kuai Liu
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China
| | - Zhenbo Li
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China
| | - Jianyue Guan
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China
| | - Huiling Song
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China
| | - Wei Wei
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China
| | - Yanhong Ge
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China
| | - Qiong Fan
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 910 Hengshan Road, Shanghai, 200030, China
| | - Wei Bao
- Department of Obstetrics and Gynecology, Shanghai General Hospital affiliated with Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China
| | - Buyong Ma
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China
| | - Zixiu Du
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China
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Xia Q, Shen J, Ding H, Liu S, Li F, Li F, Feng N. Intravenous nanocrystals: fabrication, solidification, in vivo fate, and applications for cancer therapy. Expert Opin Drug Deliv 2023; 20:1467-1488. [PMID: 37814582 DOI: 10.1080/17425247.2023.2268512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 10/05/2023] [Indexed: 10/11/2023]
Abstract
INTRODUCTION Intravenous nanocrystals (INCs) have shown intrinsic advantages in antitumor applications, particularly their properties of high drug loading, low toxicity, and controllable size. Therefore, it has a very bright application prospect as a drug delivery system. AREAS COVERED The ideal formulation design principles, fabrication, solidification, in vivo fate of INCs, the applications in drug delivery system (DDS) and the novel applications are covered in this review. EXPERT OPINION It is vital to select a suitable formulation and fabrication method to produce a stable and sterile INCs. Besides, the type of stabilizers and physical characteristics can also influence the in vivo fate of INCs, which is worthy of further studying. Based on wide researches about applications of INCs in cancer, biomimetic INCs are concerned increasingly for its favorable compatibility. The output of these studies suggested that INCs-based drug delivery could be a novel strategy for addressing the delivery of the drug that faces solubility, bioavailability, and toxicity problems.
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Affiliation(s)
- Qing Xia
- Department of Pharmaceutical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jiaqi Shen
- Department of Pharmaceutical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Huining Ding
- Department of Pharmaceutical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Siyi Liu
- Department of Pharmaceutical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Fei Li
- Department of Pharmaceutics, Shanghai Eighth People's Hospital, Shanghai, China
| | - Fengqian Li
- Department of Pharmaceutics, Shanghai Eighth People's Hospital, Shanghai, China
| | - Nianping Feng
- Department of Pharmaceutical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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14
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Marques SM, Kumar L. Factors affecting the preparation of nanocrystals: characterization, surface modifications and toxicity aspects. Expert Opin Drug Deliv 2023; 20:871-894. [PMID: 37222381 DOI: 10.1080/17425247.2023.2218084] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Accepted: 05/22/2023] [Indexed: 05/25/2023]
Abstract
INTRODUCTION The fabrication of well-defined nanocrystals in size and form is the focus of much investigation. In this work, we have critically reviewed several recent instances from the literature that shows how the production procedure affects the physicochemical properties of the nanocrystals. AREAS COVERED Scopus, MedLine, PubMed, Web of Science, and Google Scholar were searched for peer-review articles published in the past few years using different key words. Authors chose relevant publications from their files for this review. This review focuses on the range of techniques available for producing nanocrystals. We draw attention to several recent instances demonstrating the impact of various process and formulation variables that affect the nanocrystals' physicochemical properties. Moreover, various developments in the characterization techniques explored for nanocrystals concerning their size, morphology, etc. have been discussed. Last but not least, recent applications, the effect of surface modifications, and the toxicological traits of nanocrystals have also been reviewed. EXPERT OPINION The selection of an appropriate production method for the formation of nanocrystals, together with a deep understanding of the relationship between the drug's physicochemical properties, unique features of the various formulation alternatives, and anticipated in-vivo performance, would significantly reduce the risk of failure during human clinical trials that are inadequate.
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Affiliation(s)
- Shirleen Miriam Marques
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Lalit Kumar
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hajipur, Bihar, India
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Fu CP, Cai XY, Chen SL, Yu HW, Fang Y, Feng XC, Zhang LM, Li CY. Hyaluronic Acid-Based Nanocarriers for Anticancer Drug Delivery. Polymers (Basel) 2023; 15:polym15102317. [PMID: 37242892 DOI: 10.3390/polym15102317] [Citation(s) in RCA: 43] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 05/06/2023] [Accepted: 05/09/2023] [Indexed: 05/28/2023] Open
Abstract
Hyaluronic acid (HA), a main component of the extracellular matrix, is widely utilized to deliver anticancer drugs due to its biocompatibility, biodegradability, non-toxicity, non-immunogenicity and numerous modification sites, such as carboxyl and hydroxyl groups. Moreover, HA serves as a natural ligand for tumor-targeted drug delivery systems, as it contains the endocytic HA receptor, CD44, which is overexpressed in many cancer cells. Therefore, HA-based nanocarriers have been developed to improve drug delivery efficiency and distinguish between healthy and cancerous tissues, resulting in reduced residual toxicity and off-target accumulation. This article comprehensively reviews the fabrication of anticancer drug nanocarriers based on HA in the context of prodrugs, organic carrier materials (micelles, liposomes, nanoparticles, microbubbles and hydrogels) and inorganic composite nanocarriers (gold nanoparticles, quantum dots, carbon nanotubes and silicon dioxide). Additionally, the progress achieved in the design and optimization of these nanocarriers and their effects on cancer therapy are discussed. Finally, the review provides a summary of the perspectives, the lessons learned so far and the outlook towards further developments in this field.
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Affiliation(s)
- Chao-Ping Fu
- Institute of Biomaterials and Tissue Engineering & Fujian Provincial Key Laboratory of Biochemical Technology, Huaqiao University, Xiamen 361021, China
- College of Materials Science & Engineering, Huaqiao University, Xiamen 361021, China
- State Key Laboratory of Molecular Engineering of Polymers (Fudan University), Shanghai 200438, China
| | - Xing-Yu Cai
- Institute of Biomaterials and Tissue Engineering & Fujian Provincial Key Laboratory of Biochemical Technology, Huaqiao University, Xiamen 361021, China
- College of Materials Science & Engineering, Huaqiao University, Xiamen 361021, China
| | - Si-Lin Chen
- Institute of Biomaterials and Tissue Engineering & Fujian Provincial Key Laboratory of Biochemical Technology, Huaqiao University, Xiamen 361021, China
- College of Materials Science & Engineering, Huaqiao University, Xiamen 361021, China
| | - Hong-Wei Yu
- Institute of Biomaterials and Tissue Engineering & Fujian Provincial Key Laboratory of Biochemical Technology, Huaqiao University, Xiamen 361021, China
- College of Materials Science & Engineering, Huaqiao University, Xiamen 361021, China
| | - Ying Fang
- College of Materials Science & Engineering, Huaqiao University, Xiamen 361021, China
| | - Xiao-Chen Feng
- College of Materials Science & Engineering, Huaqiao University, Xiamen 361021, China
| | - Li-Ming Zhang
- School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, China
| | - Chang-Yong Li
- Institute of Biomaterials and Tissue Engineering & Fujian Provincial Key Laboratory of Biochemical Technology, Huaqiao University, Xiamen 361021, China
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16
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Singh N, Reddy KP, Das P, Kishor BK, Datta P. Complex formulation strategies to overcome the delivery hurdles of laptinib in metastatic breast cancer. J Drug Deliv Sci Technol 2023. [DOI: 10.1016/j.jddst.2023.104315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
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Preclinical and Clinical Trials of New Treatment Strategies Targeting Cancer Stem Cells in Subtypes of Breast Cancer. Cells 2023; 12:cells12050720. [PMID: 36899854 PMCID: PMC10001180 DOI: 10.3390/cells12050720] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 02/01/2023] [Accepted: 02/09/2023] [Indexed: 02/26/2023] Open
Abstract
Breast cancer (BC) can be classified into various histological subtypes, each associated with different prognoses and treatment options, including surgery, radiation, chemotherapy, and endocrine therapy. Despite advances in this area, many patients still face treatment failure, the risk of metastasis, and disease recurrence, which can ultimately lead to death. Mammary tumors, like other solid tumors, contain a population of small cells known as cancer stem-like cells (CSCs) that have high tumorigenic potential and are involved in cancer initiation, progression, metastasis, tumor recurrence, and resistance to therapy. Therefore, designing therapies specifically targeting at CSCs could help to control the growth of this cell population, leading to increased survival rates for BC patients. In this review, we discuss the characteristics of CSCs, their surface biomarkers, and the active signaling pathways associated with the acquisition of stemness in BC. We also cover preclinical and clinical studies that focus on evaluating new therapy systems targeted at CSCs in BC through various combinations of treatments, targeted delivery systems, and potential new drugs that inhibit the properties that allow these cells to survive and proliferate.
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Sharma A, Shambhwani D, Pandey S, Singh J, Lalhlenmawia H, Kumarasamy M, Singh SK, Chellappan DK, Gupta G, Prasher P, Dua K, Kumar D. Advances in Lung Cancer Treatment Using Nanomedicines. ACS OMEGA 2023; 8:10-41. [PMID: 36643475 PMCID: PMC9835549 DOI: 10.1021/acsomega.2c04078] [Citation(s) in RCA: 68] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 10/13/2022] [Indexed: 06/01/2023]
Abstract
Carcinoma of the lungs is among the most menacing forms of malignancy and has a poor prognosis, with a low overall survival rate due to delayed detection and ineffectiveness of conventional therapy. Therefore, drug delivery strategies that may overcome undesired damage to healthy cells, boost therapeutic efficacy, and act as imaging tools are currently gaining much attention. Advances in material science have resulted in unique nanoscale-based theranostic agents, which provide renewed hope for patients suffering from lung cancer. Nanotechnology has vastly modified and upgraded the existing techniques, focusing primarily on increasing bioavailability and stability of anti-cancer drugs. Nanocarrier-based imaging systems as theranostic tools in the treatment of lung carcinoma have proven to possess considerable benefits, such as early detection and targeted therapeutic delivery for effectively treating lung cancer. Several variants of nano-drug delivery agents have been successfully studied for therapeutic applications, such as liposomes, dendrimers, polymeric nanoparticles, nanoemulsions, carbon nanotubes, gold nanoparticles, magnetic nanoparticles, solid lipid nanoparticles, hydrogels, and micelles. In this Review, we present a comprehensive outline on the various types of overexpressed receptors in lung cancer, as well as the various targeting approaches of nanoparticles.
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Affiliation(s)
- Akshansh Sharma
- Department
of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Shoolini University, Solan 173229, India
| | | | - Sadanand Pandey
- Department
of Chemistry, College of Natural Sciences, Yeungnam University, Gyeongsan, Gyeongbuk 38541, South Korea
| | - Jay Singh
- Department
of Chemistry, Institute of Science, Banaras
Hindu University, Varanasi 221005, India
| | - Hauzel Lalhlenmawia
- Department
of Pharmacy, Regional Institute of Paramedical
and Nursing Sciences, Zemabawk, Aizawl, Mizoram 796017, India
| | - Murali Kumarasamy
- Department
of Biotechnology, National Institute of
Pharmaceutical Education and Research, Hajipur 844102, India
| | - Sachin Kumar Singh
- School
of Pharmaceutical Sciences, Lovely Professional
University, Phagwara 144411, India
- Faculty
of Health, Australian Research Centre in Complementary and Integrative
Medicine, University of Technology, Sydney, Ultimo-NSW 2007, Australia
| | - Dinesh Kumar Chellappan
- Department
of Life Sciences, School of Pharmacy, International
Medical University, Kuala Lumpur 57000, Malaysia
| | - Gaurav Gupta
- Department
of Pharmacology, School of Pharmacy, Suresh
Gyan Vihar University, Jaipur 302017, India
- Department
of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical
and Technical Sciences, Saveetha University, Chennai 602117, India
- Uttaranchal
Institute of Pharmaceutical Sciences, Uttaranchal
University, Dehradun 248007, India
| | - Parteek Prasher
- Department
of Chemistry, University of Petroleum &
Energy Studies, Dehradun 248007, India
| | - Kamal Dua
- Faculty
of Health, Australian Research Centre in Complementary and Integrative
Medicine, University of Technology, Sydney, Ultimo-NSW 2007, Australia
- Discipline
of Pharmacy, Graduate School of Health, University of Technology, Sydney, Ultimo-NSW 2007, Australia
| | - Deepak Kumar
- Department
of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Shoolini University, Solan 173229, India
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Pradhan R, Dubey SK, Puri A, Taliyan R. Development and validation of a stability‐indicating reversed‐phase–high‐performance liquid chromatography method for quantification of 2‐[1‐hexyloxyethyl]‐2‐devinyl pyropheophorbide‐a from lipid‐polymeric hybrid nanoparticles. SEPARATION SCIENCE PLUS 2022. [DOI: 10.1002/sscp.202200061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Affiliation(s)
- Rajesh Pradhan
- Department of Pharmacy Birla Institute of Technology and Science Pilani India
| | - Sunil Kumar Dubey
- Department of Pharmacy Birla Institute of Technology and Science Pilani India
- R&D Healthcare Division Emami Ltd. Kolkata India
| | - Anu Puri
- RNA Structure and Design Section, RNA Biology Laboratory (RBL), Center for Cancer Research National Cancer Institute – Frederick Frederick Maryland USA
| | - Rajeev Taliyan
- Department of Pharmacy Birla Institute of Technology and Science Pilani India
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20
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Kafle U, Agrawal S, Dash AK. Injectable Nano Drug Delivery Systems for the Treatment of Breast Cancer. Pharmaceutics 2022; 14:2783. [PMID: 36559276 PMCID: PMC9785637 DOI: 10.3390/pharmaceutics14122783] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 12/05/2022] [Accepted: 12/09/2022] [Indexed: 12/15/2022] Open
Abstract
Breast cancer is the most diagnosed type of cancer, with 2.26 million cases and 685,000 deaths recorded in 2020. If left untreated, this deadly disease can metastasize to distant organs, which is the reason behind its incurability and related deaths. Currently, conventional therapies are used to treat breast cancer, but they have numerous shortcomings such as low bioavailability, short circulation time, and off-target toxicity. To address these challenges, nanomedicines are preferred and are being extensively investigated for breast cancer treatment. Nanomedicines are novel drug delivery systems that can improve drug stability, aqueous solubility, blood circulation time, controlled release, and targeted delivery at the tumoral site and enhance therapeutic safety and effectiveness. Nanoparticles (NPs) can be administered through different routes. Although the injectable route is less preferred than the oral route for drug administration, it has its advantages: it helps tailor drugs with targeted moiety, boosts payload, avoids first-pass metabolism, and improves the pharmacokinetic parameters of the active pharmaceutical ingredients. Targeted delivery of nanomedicine, closer to organelles such as the mitochondria and nuclei in breast cancer, reduces the dosage requirements and the toxic effects of chemotherapeutics. This review aims to provide the current status of the recent advances in various injectable nanomedicines for targeted treatment of breast cancer.
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Affiliation(s)
- Urmila Kafle
- Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University, 2500 California Plaza, Omaha, NE 68178, USA
| | - Satish Agrawal
- Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University, 2500 California Plaza, Omaha, NE 68178, USA
| | - Alekha K Dash
- Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University, 2500 California Plaza, Omaha, NE 68178, USA
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21
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Agnihotri TG, Gomte SS, Jain A. Emerging theranostics to combat cancer: a perspective on metal-based nanomaterials. Drug Dev Ind Pharm 2022; 48:585-601. [PMID: 36448770 DOI: 10.1080/03639045.2022.2153862] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
Abstract
OBJECTIVE Theranostics, encompassing diagnostics and therapeutics, has emerged as a critical component of cancer treatment. Metal-based theranostics is one such next-generation nanotechnology-based drug delivery system with a myriad of benefits in pre-clinical and clinical medication for the deadly diseases like cancer, where early detection can actually be life-saving. SIGNIFICANCE Metal theranostics have shown promising outcomes in terms of anticancer medication monitoring, targeted drug delivery, and simultaneous detection and treatment of early-stage cancer. METHODS For collection of literature data, different search engines including Google scholar, SciFinder, PubMed, ScienceDirect have been employed. With key words like, cancer, theranostics, metal nanoparticles relevant and appropriate data have been generated. RESULTS Noninvasive administration of the active drug is made possible by theranostics nanoparticulate systems' ability to aggregate at the tumor site and offer morphological and biochemical characteristics of the tumor site. The recent advancement of metal-based theranostics including metallic nanoparticles, metal oxides, metal sulfides, nanocomposites, etc. has been explored at length in this article. CONCLUSION The review highlights emerging applications in terms of molecular imaging, targeted therapy and different diagnostic approaches of metal theranostics. Possible challenges faced by nanotheranostics in terms of clinical immersion and toxicological aspects which need to be addressed at depth are also discussed at the end.
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Affiliation(s)
- Tejas Girish Agnihotri
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gujarat, India
| | - Shyam Sudhakar Gomte
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gujarat, India
| | - Aakanchha Jain
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gujarat, India
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22
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Jia Y, Chen S, Wang C, Sun T, Yang L. Hyaluronic acid-based nano drug delivery systems for breast cancer treatment: Recent advances. Front Bioeng Biotechnol 2022; 10:990145. [PMID: 36091467 PMCID: PMC9449492 DOI: 10.3389/fbioe.2022.990145] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Accepted: 08/05/2022] [Indexed: 11/13/2022] Open
Abstract
Breast cancer (BC) is the most common malignancy among females worldwide, and high resistance to drugs and metastasis rates are the leading causes of death in BC patients. Releasing anti-cancer drugs precisely to the tumor site can improve the efficacy and reduce the side effects on the body. Natural polymers are attracting extensive interest as drug carriers in treating breast cancer. Hyaluronic acid (HA) is a natural polysaccharide with excellent biocompatibility, biodegradability, and non-immunogenicity and is a significant component of the extracellular matrix. The CD44 receptor of HA is overexpressed in breast cancer cells and can be targeted to breast tumors. Therefore, many researchers have developed nano drug delivery systems (NDDS) based on the CD44 receptor tumor-targeting properties of HA. This review examines the application of HA in NDDSs for breast cancer in recent years. Based on the structural composition of NDDSs, they are divided into HA NDDSs, Modified HA NDDSs, and HA hybrid NDDSs.
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Affiliation(s)
- Yufeng Jia
- Department of Breast Medicine, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China
| | - Siwen Chen
- Center for Molecular Science and Engineering, College of Science, Northeastern University, Shenyang, China
- NHC Key Laboratory of Reproductive Health and Medical Genetics (China Medical University), Liaoning Research Institute of Family Planning (The Reproductive Hospital of China Medical University), Shenyang, China
| | - Chenyu Wang
- Department of Information Management, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China
| | - Tao Sun
- Department of Breast Medicine, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China
- *Correspondence: Tao Sun, ; Liqun Yang,
| | - Liqun Yang
- NHC Key Laboratory of Reproductive Health and Medical Genetics (China Medical University), Liaoning Research Institute of Family Planning (The Reproductive Hospital of China Medical University), Shenyang, China
- *Correspondence: Tao Sun, ; Liqun Yang,
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23
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Xu H, Zhang F, Gao X, Zhou Q, Zhu L. Fate decisions of breast cancer stem cells in cancer progression. Front Oncol 2022; 12:968306. [PMID: 36046046 PMCID: PMC9420991 DOI: 10.3389/fonc.2022.968306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 07/26/2022] [Indexed: 11/13/2022] Open
Abstract
Breast cancer has a marked recurrence and metastatic trait and is one of the most prevalent malignancies affecting women’s health worldwide. Tumor initiation and progression begin after the cell goes from a quiescent to an activated state and requires different mechanisms to act in concert to regulate t a specific set of spectral genes for expression. Cancer stem cells (CSCs) have been proven to initiate and drive tumorigenesis due to their capability of self-renew and differentiate. In addition, CSCs are believed to be capable of causing resistance to anti-tumor drugs, recurrence and metastasis. Therefore, exploring the origin, regulatory mechanisms and ultimate fate decision of CSCs in breast cancer outcomes has far-reaching clinical implications for the development of breast cancer stem cell (BCSC)-targeted therapeutic strategies. In this review, we will highlight the contribution of BCSCs to breast cancer and explore the internal and external factors that regulate the fate of BCSCs.
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Kumar A, Valamla B, Thakor P, Chary PS, Rajana N, Mehra NK. Development and evaluation of nanocrystals loaded hydrogel for topical application. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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25
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Kunde SS, Wairkar S. Targeted delivery of albumin nanoparticles for breast cancer: A review. Colloids Surf B Biointerfaces 2022; 213:112422. [PMID: 35231688 DOI: 10.1016/j.colsurfb.2022.112422] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 02/12/2022] [Accepted: 02/20/2022] [Indexed: 02/07/2023]
Abstract
Breast cancer has been identified as one of the most common cancers diagnosed in women. Various nanotechnology platforms offering unique features are considered in breast cancer treatment. Albumin is a versatile biodegradable, biocompatible, non-toxic and non-immunogenic protein nanocarrier. These characteristics attracted strong attention to fabricate albumin nanoparticles to deliver chemotherapeutic agents without major adverse effects. Albumin nanoparticles can undergo surface modifications using different ligands promoting tumor-targeted drug delivery. Moreover, multifunctional albumin nanoparticle is an upcoming strategy to attain efficient cancer therapy. This review gives an account of the potential albumin nanoparticles developed for chemotherapeutic drug delivery and its targeted approach for breast cancer. It also covers different multifunctional therapies available using albumin nanoparticles as breast cancer theranostics.
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Affiliation(s)
- Shalvi Sinai Kunde
- Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKMs NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai, Maharashtra 400056, India
| | - Sarika Wairkar
- Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKMs NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai, Maharashtra 400056, India.
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Picheth GF, Ganzella FADO, Filizzola JO, Canquerino YK, Cardoso GC, Collini MB, Colauto LB, Figueroa-Magalhães MC, Cavalieri EA, Klassen G. Ligand-mediated nanomedicines against breast cancer: a review. Nanomedicine (Lond) 2022; 17:645-664. [PMID: 35438008 DOI: 10.2217/nnm-2021-0473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Ligand-mediated targeting represents the cutting edge in precision-guided therapy for several diseases. Surface engineering of nanomedicines with ligands exhibiting selective or tailored affinity for overexpressed biomolecules of a specific disease may increase therapeutic efficiency and reduce side effects and recurrence. This review focuses on newly developed approaches and strategies to improve treatment and overcome the mechanisms associated with breast cancer resistance.
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Affiliation(s)
- Guilherme F Picheth
- Department of Basic Pathology, Federal University of Paraná, Curitiba, Paraná, Brazil.,School of Medicine, Pontifical Catholic University of Paraná, Curitiba, Paraná, Brazil
| | | | - João Oc Filizzola
- Department of Basic Pathology, Federal University of Paraná, Curitiba, Paraná, Brazil
| | - Yan K Canquerino
- Department of Basic Pathology, Federal University of Paraná, Curitiba, Paraná, Brazil
| | - Gabriela C Cardoso
- Department of Basic Pathology, Federal University of Paraná, Curitiba, Paraná, Brazil
| | - Michelle B Collini
- Department of Basic Pathology, Federal University of Paraná, Curitiba, Paraná, Brazil
| | - Leonardo B Colauto
- Department of Basic Pathology, Federal University of Paraná, Curitiba, Paraná, Brazil
| | | | - Edneia Asr Cavalieri
- Department of Basic Pathology, Federal University of Paraná, Curitiba, Paraná, Brazil
| | - Giseli Klassen
- Department of Basic Pathology, Federal University of Paraná, Curitiba, Paraná, Brazil
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Zingale E, Bonaccorso A, Carbone C, Musumeci T, Pignatello R. Drug Nanocrystals: Focus on Brain Delivery from Therapeutic to Diagnostic Applications. Pharmaceutics 2022; 14:691. [PMID: 35456525 PMCID: PMC9024479 DOI: 10.3390/pharmaceutics14040691] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 03/10/2022] [Accepted: 03/15/2022] [Indexed: 02/01/2023] Open
Abstract
The development of new drugs is often hindered by low solubility in water, a problem common to nearly 90% of natural and/or synthetic molecules in the discovery pipeline. Nanocrystalline drug technology involves the reduction in the bulk particle size down to the nanosize range, thus modifying its physico-chemical properties with beneficial effects on drug bioavailability. Nanocrystals (NCs) are carrier-free drug particles surrounded by a stabilizer and suspended in an aqueous medium. Due to high drug loading, NCs maintain a potent therapeutic concentration to produce desirable pharmacological action, particularly useful in the treatment of central nervous system (CNS) diseases. In addition to the therapeutic purpose, NC technology can be applied for diagnostic scope. This review aims to provide an overview of NC application by different administration routes, especially focusing on brain targeting, and with a particular attention to therapeutic and diagnostic fields. NC therapeutic applications are analyzed for the most common CNS pathologies (i.e., Parkinson's disease, psychosis, Alzheimer's disease, etc.). Recently, a growing interest has emerged from the use of colloidal fluorescent NCs for brain diagnostics. Therefore, the use of NCs in the imaging of brain vessels and tumor cells is also discussed. Finally, the clinical effectiveness of NCs is leading to an increasing number of FDA-approved products, among which the NCs approved for neurological disorders have increased.
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Affiliation(s)
- Elide Zingale
- Laboratory of Drug Delivery Technology, Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy; (E.Z.); (C.C.); (T.M.); (R.P.)
| | - Angela Bonaccorso
- Laboratory of Drug Delivery Technology, Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy; (E.Z.); (C.C.); (T.M.); (R.P.)
- NANO-i—Research Centre on Ocular Nanotechnology, University of Catania, 95125 Catania, Italy
| | - Claudia Carbone
- Laboratory of Drug Delivery Technology, Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy; (E.Z.); (C.C.); (T.M.); (R.P.)
- NANO-i—Research Centre on Ocular Nanotechnology, University of Catania, 95125 Catania, Italy
| | - Teresa Musumeci
- Laboratory of Drug Delivery Technology, Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy; (E.Z.); (C.C.); (T.M.); (R.P.)
- NANO-i—Research Centre on Ocular Nanotechnology, University of Catania, 95125 Catania, Italy
| | - Rosario Pignatello
- Laboratory of Drug Delivery Technology, Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy; (E.Z.); (C.C.); (T.M.); (R.P.)
- NANO-i—Research Centre on Ocular Nanotechnology, University of Catania, 95125 Catania, Italy
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Zhao D, Hu C, Fu Q, Lv H. Combined chemotherapy for triple negative breast cancer treatment by paclitaxel and niclosamide nanocrystals loaded thermosensitive hydrogel. Eur J Pharm Sci 2021; 167:105992. [PMID: 34517104 DOI: 10.1016/j.ejps.2021.105992] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 09/03/2021] [Accepted: 09/05/2021] [Indexed: 11/19/2022]
Abstract
Triple negative breast cancer (TNBC) is the most dangerous subtype of breast cancer accompanying by unfavorable prognosis due to lack of specific therapeutic targets. Paclitaxel (PTX) is the first-line chemotherapeutic drug for TNBC and niclosamide (NLM) was identified as an inhibitor for TNBC and breast cancer stem cells (BCSCs). Intratumoral drug delivery system was a hopeful alternative for chemotherapeutic drug administration due to its targeting efficiency with lower systemic toxicity. Herein, an injectable PTX nanocrystals (PTX-NCs) and NLM nanocrystals (NLM-NCs) co-loaded PLGA-PEG-PLGA thermosensitive hydrogel (PNNCs-Ts Gel) was designed for TNBC intratumoral treatment. The final formulation realized high drug loading and appropriate particle size. PNNCs-Ts Gel displayed sustained drug release for up to 8 days in vitro. In vitro antitumor tests observed synergetic effects of combined therapy in terms of inhibiting cell proliferation and migration, inducing apoptosis. In vivo combined therapy presented a tumor growth inhibition rate about 68.8% and desired safety. Moreover, tumors after PNNCs-Ts Gel intratumoral injection possessed the lowest ratio of BCSCs, exhibiting this formulation had good ability in suppressing BCSCs and therefore could possibly prevent TNBC recurrence and metastasis. These results suggested that PNNCs-Ts Gel could be a promising strategy for TNBC treatment.
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Affiliation(s)
- Deqian Zhao
- Beijing Leadingpharm Medical technology development Co. Ltd, Beijing 100094, China
| | - Chenlu Hu
- Department of Pharmaceutics, China Pharmaceutical University, Nanjing 211198, China
| | - Qiang Fu
- Department of Pharmaceutics, China Pharmaceutical University, Nanjing 211198, China.
| | - Huixia Lv
- Department of Pharmaceutics, China Pharmaceutical University, Nanjing 211198, China.
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Huang X, Lu Y, Guo M, Du S, Han N. Recent strategies for nano-based PTT combined with immunotherapy: from a biomaterial point of view. Theranostics 2021; 11:7546-7569. [PMID: 34158866 PMCID: PMC8210617 DOI: 10.7150/thno.56482] [Citation(s) in RCA: 127] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Accepted: 05/23/2021] [Indexed: 01/04/2023] Open
Abstract
Cancer has been a great threat to humans for decades. Due to the limitations of monotherapy, combinational therapies such as photothermal therapy (PTT) and immunotherapy have gained increasing attention with expectation to overcome the shortfalls of each other and obtain satisfactory therapeutic outcomes. PTT can inhibit primary tumors by thermal ablation but usually fails to achieve complete eradication and cannot prevent metastasis and recurrence. Meanwhile, the efficacy of immunotherapy is usually attenuated by the weak immunogenicity of tumor and the immunosuppressive tumor microenvironment (ITM). Therefore, many recent studies have attempted to synergize PTT with immunotherapy in order to enhance the therapeutic efficacy. In this review, we aim to summarize the cutting-edge strategies in combining nano-based PTT with immunotherapy for cancer treatment. Herein, the combination strategies were mainly classified into four categories, including 1) nano-based PTT combined with antigens to induce host immune responses; 2) nano-based PTT in combination with immune adjuvants acting as in situ vaccines; 3) nano-based PTT synergized with immune checkpoint blockade or other regulators to relieve the ITM; 4) nano-based PTT combined with CAR-T therapy or cytokine therapy for tumor treatment. The characteristics of various photothermal agents and nanoplatforms as well as the immunological mechanisms for the synergism were also introduced in detail. Finally, we discussed the existing challenges and future prospects in combined PTT and immunotherapy.
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Affiliation(s)
| | | | | | - Shouying Du
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Ning Han
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
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Shukla RP, Urandur S, Banala VT, Marwaha D, Gautam S, Rai N, Singh N, Tiwari P, Shukla P, Mishra PR. Development of putrescine anchored nano-crystalsomes bearing doxorubicin and oleanolic acid: deciphering their role in inhibiting metastatic breast cancer. Biomater Sci 2021; 9:1779-1794. [PMID: 33443267 DOI: 10.1039/d0bm01033b] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Angiogenesis driven tumor initiation and progression calls for a targeted therapy. Moreover, combined chemotherapy supplements the therapy to act on the cause of concern. In this study, we aimed to develop a targeted crystalsomes approach to delineate tumor cells against normal cells. Self-assembled crystalline monodispersed nanosized polyethylene-polyethylene glycol (PE-PEG)-based hollow crystalsomes were modified with pluronylated putrescine (Put-PF) and loaded with doxorubicin (Dox), synergistically in combination with oleanolic acid (OA) to target the glypican-1 (gp-1) receptor on tumor cells. The developed crystalsomes (Put-D + O@NCs) showed increased intracellular accumulation of Dox and OA in a synergistic combination inside the MDA-MB-231 cell lines. The developed crystalsomes marked an enhanced depolarization of the mitochondrial membrane potential and cell cycle arrest leading to apoptosis. Furthermore, the proposed therapy has a greater anti-angiogenesis activity with vascular endothelial growth factor (VEGF) dependent modulation in the proliferation, invasion, migration and tube formation of human endothelial umbilical vein cells (HUVECs) in vitro and in vivo in a BALB/c mouse model. Interestingly, the perseverance of the tumor boundary, inhibiting the expression and activity of the matrix metalloproteinase (MMPs) (>5.2-fold) with suppressed degradation of the extracellular matrix paves the way for significant inhibition of metastases. However, an intravenously administered Put-D + O@NCs showed an improved pharmacokinetic profile and exquisite inhibition of the 4T1 induced tumor with a significantly lower toxicity. In a nutshell, these findings highlight the important role of Put in the gp-1 receptor for specific targeting and synergistic delivery of Dox and OA through crystalsomes as a potential approach for the treatment of metastatic breast cancer using combined chemotherapy.
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Affiliation(s)
- Ravi Prakash Shukla
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute Lucknow, India.
| | - Sandeep Urandur
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute Lucknow, India.
| | - Venkatesh Teja Banala
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute Lucknow, India.
| | - Disha Marwaha
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute Lucknow, India.
| | - Shalini Gautam
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute Lucknow, India.
| | - Nikhil Rai
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute Lucknow, India.
| | - Neha Singh
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute Lucknow, India.
| | - Pratiksha Tiwari
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute Lucknow, India.
| | - Prashant Shukla
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute Lucknow, India.
| | - Prabhat Ranjan Mishra
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute Lucknow, India.
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Malavia N, Kuche K, Ghadi R, Jain S. A bird's eye view of the advanced approaches and strategies for overshadowing triple negative breast cancer. J Control Release 2020; 330:72-100. [PMID: 33321156 DOI: 10.1016/j.jconrel.2020.12.012] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 12/07/2020] [Accepted: 12/09/2020] [Indexed: 12/12/2022]
Abstract
Triple negative breast cancer (TNBC) is one of the most aggressive form of breast cancer. It is characterized by the absence of estrogen, progesterone and human epidermal growth factor receptors. The main issue with TNBC is that it exhibits poor prognosis, high risk of relapse, short progression-free survival and low overall survival in patients. This is because the conventional therapy used for managing TNBC has issues pertaining to poor bioavailability, lower cellular uptake, increased off-target effects and development of resistance. To overcome such pitfalls, several other approaches are explored. In this context, the present manuscript showcases three of the most widely used approaches which are (i) nanotechnology-based approach; (ii) gene therapy approach and (iii) Phytochemical-based approach. The ultimate focus is to present and explain the insightful reports based on these approaches. Further, the review also expounds on the identified molecular targets and novel targeting ligands which are explored for managing TNBC effectively. Thus, in a nutshell, the review tries to highlight these existing treatment approaches which might inspire for future development of novel therapies with a potential of overshadowing TNBC.
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Affiliation(s)
- Nilesh Malavia
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, Mohali, Punjab, India
| | - Kaushik Kuche
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, Mohali, Punjab, India
| | - Rohan Ghadi
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, Mohali, Punjab, India
| | - Sanyog Jain
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, Mohali, Punjab, India.
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Kudarha RR, Sawant KK. Chondroitin sulfate conjugation facilitates tumor cell internalization of albumin nanoparticles for brain-targeted delivery of temozolomide via CD44 receptor-mediated targeting. Drug Deliv Transl Res 2020; 11:1994-2008. [PMID: 33026610 DOI: 10.1007/s13346-020-00861-x] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/17/2020] [Indexed: 12/20/2022]
Abstract
In the present investigation, temozolomide (TMZ) loaded chondroitin sulfate conjugated albumin nanoparticles (CS-TNPs) were fabricated by desolvation method were chondroitin sulfate (CS) was used as the surface exposed ligand to achieve CD44 receptor mediated targeting of brain tumor. The developed CS-TNPs were characterized for particle size, zeta potential, entrapment efficiency and drug loading and evaluated by FTIR, DSC, XRD and TEM analysis. BBB (blood brain barrier) passage study using in vitro BBB model indicated that CS-TNPs were able to efficiently cross the BBB. Cell viability assay data demonstrated higher cytotoxicity of CS-TNPs as compared with pure TMZ. The CD44 receptor blocking assay and receptor poisoning assay in U87 MG cells confirmed the CD44 receptor and endocytosis-mediated (caveolae pathway) uptake of CS-TNPs. CS-TNPs were able to generate ROS in U87 MG cells. In vivo pharmacokinetic and biodistribution studies were performed in Wistar rats. In vivo results revealed significant enhancement in pharmacokinetic profile of CS-TNPs as compared with TMZ alone. Biodistribution results demonstrated higher accumulation of TMZ in the brain by CS-TNPs as compared with the pure drug that confirmed the brain targeting ability of nanoparticles. From all obtained results, it may be concluded that CS-TNPs are promising carrier to deliver TMZ to the brain for targeted therapy of brain tumor. Graphical abstract.
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Affiliation(s)
- Ritu R Kudarha
- Drug Delivery Research Laboratory, Centre of Relevance and Excellence in NDDS, Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Donor's Plaza, Fathegunj, Vadodara, 390002, India
| | - Krutika K Sawant
- Drug Delivery Research Laboratory, Centre of Relevance and Excellence in NDDS, Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Donor's Plaza, Fathegunj, Vadodara, 390002, India.
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Walcher L, Kistenmacher AK, Suo H, Kitte R, Dluczek S, Strauß A, Blaudszun AR, Yevsa T, Fricke S, Kossatz-Boehlert U. Cancer Stem Cells-Origins and Biomarkers: Perspectives for Targeted Personalized Therapies. Front Immunol 2020; 11:1280. [PMID: 32849491 PMCID: PMC7426526 DOI: 10.3389/fimmu.2020.01280] [Citation(s) in RCA: 567] [Impact Index Per Article: 113.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Accepted: 05/20/2020] [Indexed: 02/06/2023] Open
Abstract
The use of biomarkers in diagnosis, therapy and prognosis has gained increasing interest over the last decades. In particular, the analysis of biomarkers in cancer patients within the pre- and post-therapeutic period is required to identify several types of cells, which carry a risk for a disease progression and subsequent post-therapeutic relapse. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and can cause relapses. At the time point of tumor initiation, CSCs originate from either differentiated cells or adult tissue resident stem cells. Due to their importance, several biomarkers that characterize CSCs have been identified and correlated to diagnosis, therapy and prognosis. However, CSCs have been shown to display a high plasticity, which changes their phenotypic and functional appearance. Such changes are induced by chemo- and radiotherapeutics as well as senescent tumor cells, which cause alterations in the tumor microenvironment. Induction of senescence causes tumor shrinkage by modulating an anti-tumorigenic environment in which tumor cells undergo growth arrest and immune cells are attracted. Besides these positive effects after therapy, senescence can also have negative effects displayed post-therapeutically. These unfavorable effects can directly promote cancer stemness by increasing CSC plasticity phenotypes, by activating stemness pathways in non-CSCs, as well as by promoting senescence escape and subsequent activation of stemness pathways. At the end, all these effects can lead to tumor relapse and metastasis. This review provides an overview of the most frequently used CSC markers and their implementation as biomarkers by focussing on deadliest solid (lung, stomach, liver, breast and colorectal cancers) and hematological (acute myeloid leukemia, chronic myeloid leukemia) cancers. Furthermore, it gives examples on how the CSC markers might be influenced by therapeutics, such as chemo- and radiotherapy, and the tumor microenvironment. It points out, that it is crucial to identify and monitor residual CSCs, senescent tumor cells, and the pro-tumorigenic senescence-associated secretory phenotype in a therapy follow-up using specific biomarkers. As a future perspective, a targeted immune-mediated strategy using chimeric antigen receptor based approaches for the removal of remaining chemotherapy-resistant cells as well as CSCs in a personalized therapeutic approach are discussed.
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Affiliation(s)
- Lia Walcher
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
| | - Ann-Kathrin Kistenmacher
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
| | - Huizhen Suo
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Reni Kitte
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
| | - Sarah Dluczek
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
| | - Alexander Strauß
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
| | - André-René Blaudszun
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
| | - Tetyana Yevsa
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Stephan Fricke
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
| | - Uta Kossatz-Boehlert
- Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
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Kumar M, Jha A, Dr M, Mishra B. Targeted drug nanocrystals for pulmonary delivery: a potential strategy for lung cancer therapy. Expert Opin Drug Deliv 2020; 17:1459-1472. [PMID: 32684002 DOI: 10.1080/17425247.2020.1798401] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Lung cancer and metastases are major concerns worldwide. Although systemic chemotherapy is the recommended treatment, it is associated with various disadvantages, including nonselective drug distribution and systemic toxicity. In contrast, the pulmonary route ensures the localized delivery of drugs to the lung. Still, the pulmonary route is prone to clearance, limited drug dissolution, and local toxicity to healthy lung cells. Drug nanocrystals provide a potential strategy to enhance the therapeutic efficacy and mitigate the limitations of pulmonary delivery. AREAS COVERED The development and potential application of nanocrystals in pulmonary delivery, their role in overcoming associated barriers, and strategies for site-specific and stimuli-responsive pulmonary delivery are outlined. This review also traces different in-vitro pulmonary models for assessments of the performance of drug nanocrystals and nanocrystals loaded carriers in pulmonary delivery. EXPERT OPINION Enhanced stability, high aerosolization performance, better particle size distribution, improved penetration, sustained release of the drug, and minimal excipients usage makes drug nanocrystal an ideal candidate for pulmonary delivery. Besides, drug nanocrystals may provide selective cellular internalization with minimum clearance and maximum deposition. Furthermore, surface modified nanocrystals and nanocrystals in nanocarriers can exhibit a more prolonged, and site-specific release of the drug to cancer cells in the lungs.
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Affiliation(s)
- Manish Kumar
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU) , Varanasi, India
| | - Abhishek Jha
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU) , Varanasi, India
| | - Madhu Dr
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU) , Varanasi, India
| | - Brahmeshwar Mishra
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU) , Varanasi, India
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Sui J, Zhao M, Yang Y, Guo Z, Ma M, Xu Z, Liang J, Sun Y, Fan Y, Zhang X. Acid-labile polysaccharide prodrug via lapatinib-sensitizing effect substantially prevented metastasis and postoperative recurrence of triple-negative breast cancer. NANOSCALE 2020; 12:13567-13581. [PMID: 32555923 DOI: 10.1039/d0nr03395b] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Surgical resection and chemotherapy are routinely performed for triple-negative breast cancer (TNBC) because it is insensitive to endocrine therapy and molecular targeted therapy. Here, the optimal surface charge (-28 mV) and particle size (51 nm) enabled the acid-labile hyaluronic acid pullulan prodrug (HPP)-doxorubicin (Dox)/lapatinib (Lap) conjugate to circulate in the blood for a lengthy period of time and enhance the electron paramagnetic resonance effect, while the targeted molecule hyaluronic acid accelerated CD44 receptor-mediated 4T1 cell internalization. The inefficient anti-proliferation capability of Lap increased more than 10-fold after sensitization of Dox to metastatic 4T1 cells, while cellular uptake significantly increased, and cell viability dramatically decreased to nearly 20% of the free Dox group. Furthermore, HPP-Dox/Lap more effectively inhibited lateral mobility, vertical migration, and invasion ability of 4T1 cells. The ex vivo biodistribution of representative Dox indicated that Lap obviously facilitated the intratumoral infiltration and accumulation. The in vivo research revealed that there were overwhelming advantages in using HPP-Dox/Lap to inhibit tumor growth, progression, and lung metastasis even at a low dosage (1 mg kg-1), and it decreased postoperative recurrence and pulmonary metastatic nodules. Because of the excellent biosafety and visible therapeutic effect on the 4T1 metastasis and recurrence model, there is great potential value for HPP-Dox/Lap to be used to treat metastatic TNBC.
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Affiliation(s)
- Junhui Sui
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610064, China.
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Shi W, Hass B, Kuss MA, Zhang H, Ryu S, Zhang D, Li T, Li YL, Duan B. Fabrication of versatile dynamic hyaluronic acid-based hydrogels. Carbohydr Polym 2020; 233:115803. [DOI: 10.1016/j.carbpol.2019.115803] [Citation(s) in RCA: 106] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 12/24/2019] [Accepted: 12/27/2019] [Indexed: 12/11/2022]
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Hao YJ, Sun HB, Li HW, Chen BJ, Chen XL, Ma L, Li YL. Application of positive behavior management in patients after breast cancer surgery. World J Clin Cases 2020; 8:689-699. [PMID: 32149053 PMCID: PMC7052560 DOI: 10.12998/wjcc.v8.i4.689] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2019] [Revised: 12/26/2019] [Accepted: 01/14/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND As a radical treatment, breast cancer surgery has a positive psychological impact on most patients. However, some patients do not have a clear understanding of the disease, which requires a more scientific and comprehensive consideration during clinical intervention and are based on cognition. The positive behavior management model is based on this kind of background-derived new interventions, which can better serve the clinical rehabilitation process of patients. The positive behavior management model based on cognitive architecture is a new type of intervention derived from this background, which can better serve the clinical rehabilitation process of patients.
AIM To analyze the influence of a positive behavior management model based on cognitive framework on the degree of hope and self-efficacy of patients with breast cancer surgery.
METHODS Eighty-four patients with breast cancer who underwent surgical treatment in our hospital from August 2016 to December 2018 were included in the study. The patients were divided into the experimental group (n = 42) and control group (n = 42) by random number table grouping. The control group received traditional nursing intervention, while the experimental group received a positive behavior management model based on cognitive framework based on the traditional intervention of the control group. General Self-efficacy Scale, Herth Hope Scale, Self-Rating Anxiety Scale, Self-Rating Depression Scale and Cancer Patient Specific Scale were used to evaluate the two groups before and 1 wk after intervention.
RESULTS After the intervention, self-efficacy and hope level of the experimental group were significantly higher than those of the control group (P < 0.05). The Self-Rating Anxiety Scale and Self-Rating Depression Scale scores in the experimental group were significantly lower than those in the control group (P < 0.05). There was no significant difference in the quality of life scores between the two groups before intervention (P > 0.05). The quality of life scores in all aspects in the experimental group after intervention were significantly higher than those in the control group (P < 0.05).
CONCLUSION The positive behavior management model based on cognitive framework applied to patients with breast cancer surgery improved hope for treatment and self-efficacy, reduced negative emotion, and improved quality of life.
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Affiliation(s)
- Ying-Jie Hao
- Department of Breast Surgery, the Third Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, Heilongjiang Province, China
| | - Hui-Bo Sun
- Department of Breast Surgery, the Third Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, Heilongjiang Province, China
| | - Hong-Wei Li
- Department of Breast Surgery, the Third Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, Heilongjiang Province, China
| | - Bing-Jie Chen
- Department of Nursing, the Third Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, Heilongjiang Province, China
| | - Xiu-Li Chen
- Department of Nursing, the Third Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, Heilongjiang Province, China
| | - Lin Ma
- Department of Nursing, the Third Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, Heilongjiang Province, China
| | - Ying-Li Li
- Department of Otolaryngology, the Third Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, Heilongjiang Province, China
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Alqaraghuli HGJ, Kashanian S, Rafipour R. A Review on Targeting Nanoparticles for Breast Cancer. Curr Pharm Biotechnol 2020; 20:1087-1107. [PMID: 31364513 DOI: 10.2174/1389201020666190731130001] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 07/10/2019] [Accepted: 07/12/2019] [Indexed: 12/11/2022]
Abstract
Chemotherapeutic agents have been used extensively in breast cancer remedy. However, most anticancer drugs cannot differentiate between cancer cells and normal cells, leading to toxic side effects. Also, the resulted drug resistance during chemotherapy reduces treatment efficacy. The development of targeted drug delivery offers great promise in breast cancer treatment both in clinical applications and in pharmaceutical research. Conjugation of nanocarriers with targeting ligands is an effective therapeutic strategy to treat cancer diseases. In this review, we focus on active targeting methods for breast cancer cells through the use of chemical ligands such as antibodies, peptides, aptamers, vitamins, hormones, and carbohydrates. Also, this review covers all information related to these targeting ligands, such as their subtypes, advantages, disadvantages, chemical modification methods with nanoparticles and recent published studies (from 2015 to present). We have discussed 28 different targeting methods utilized for targeted drug delivery to breast cancer cells with different nanocarriers delivering anticancer drugs to the tumors. These different targeting methods give researchers in the field of drug delivery all the information and techniques they need to develop modern drug delivery systems.
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Affiliation(s)
- Hasanain Gomhor J Alqaraghuli
- Faculty of Chemistry, Razi University, Kermanshah, Iran.,Department of Sciences, College of Basic Education, Al- Muthanna University, Al-Muthanna, Iraq
| | - Soheila Kashanian
- Faculty of Chemistry, Sensor and Biosensor Research Center (SBRC) & Nanoscience and Nanotechnology Research Center (NNRC), Razi University, Kermanshah, Iran.,Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ronak Rafipour
- Department of Chemistry, Kermanshah Branch, Islamic Azad University, Kermanshah, Iran
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Zhou X, Shi K, Hao Y, Yang C, Zha R, Yi C, Qian Z. Advances in nanotechnology-based delivery systems for EGFR tyrosine kinases inhibitors in cancer therapy. Asian J Pharm Sci 2020; 15:26-41. [PMID: 32175016 PMCID: PMC7066044 DOI: 10.1016/j.ajps.2019.06.001] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Revised: 05/30/2019] [Accepted: 06/14/2019] [Indexed: 02/05/2023] Open
Abstract
Oral tyrosine kinase inhibitors (TKIs) against epidermal growth factor receptor (EGFR) family have been introduced into the clinic to treat human malignancies for decades. Despite superior properties of EGFR-TKIs as small molecule targeted drugs, their applications are still restricted due to their low solubility, capricious oral bioavailability, large requirement of daily dose, high binding tendency to plasma albumin and initial/acquired drug resistance. Nanotechnology is a promising tool to improve efficacy of these drugs. Through non-oral routes. Various nanotechnology-based delivery approaches have been developed for providing efficient delivery of EGFR-TKIs with a better pharmacokinetic profile and tissue-targeting ability. This review aims to indicate the advantage of nanocarriers for EGFR-TKIs delivery.
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Affiliation(s)
| | | | | | | | | | | | - Zhiyong Qian
- Department of Medical Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
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40
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Shukla RP, Dewangan J, Urandur S, Banala VT, Diwedi M, Sharma S, Agrawal S, Rath SK, Trivedi R, Mishra PR. Multifunctional hybrid nanoconstructs facilitate intracellular localization of doxorubicin and genistein to enhance apoptotic and anti-angiogenic efficacy in breast adenocarcinoma. Biomater Sci 2020; 8:1298-1315. [DOI: 10.1039/c9bm01246j] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The progressive development of tumors leading to angiogenesis marks the advancement of cancer which requires specific targeted treatment preferably with combination chemotherapy.
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Affiliation(s)
- Ravi Prakash Shukla
- Division of Pharmaceutics and Pharmacokinetics
- CSIR-Central Drug Research Institute Lucknow
- India
| | - Jayant Dewangan
- Division of Toxicology
- CSIR-Central Drug Research Institute Lucknow
- India
| | - Sandeep Urandur
- Division of Pharmaceutics and Pharmacokinetics
- CSIR-Central Drug Research Institute Lucknow
- India
| | - Venkatesh Teja Banala
- Division of Pharmaceutics and Pharmacokinetics
- CSIR-Central Drug Research Institute Lucknow
- India
| | - Monika Diwedi
- Division of Pharmaceutics and Pharmacokinetics
- CSIR-Central Drug Research Institute Lucknow
- India
| | - Shweta Sharma
- Division of Pharmaceutics and Pharmacokinetics
- CSIR-Central Drug Research Institute Lucknow
- India
| | - Sristi Agrawal
- Division of Pharmaceutics and Pharmacokinetics
- CSIR-Central Drug Research Institute Lucknow
- India
| | | | - Ritu Trivedi
- Division of Endocrinology
- CSIR-Central Drug Research Institute Lucknow
- India
| | - Prabhat Ranjan Mishra
- Division of Pharmaceutics and Pharmacokinetics
- CSIR-Central Drug Research Institute Lucknow
- India
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41
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Bhaskaran NA, Chevala NT, Kumar L. Nanopharmacokinetics, pharmacodynamics (PK/PD), and clinical relationship. NANOMEDICINES FOR BREAST CANCER THERANOSTICS 2020:245-268. [DOI: 10.1016/b978-0-12-820016-2.00011-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Afzal M, Ameeduzzafar, Alharbi KS, Alruwaili NK, Al-Abassi FA, Al-Malki AAL, Kazmi I, Kumar V, Kamal MA, Nadeem MS, Aslam M, Anwar F. Nanomedicine in treatment of breast cancer - A challenge to conventional therapy. Semin Cancer Biol 2019; 69:279-292. [PMID: 31870940 DOI: 10.1016/j.semcancer.2019.12.016] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 11/18/2019] [Accepted: 12/03/2019] [Indexed: 02/06/2023]
Abstract
Amongst the various types of cancer, breast cancer is a highly heterogeneous disease and known as the leading cause of death among women globally. The extensive interdisciplinary investigation in nanotechnology and cancer biomedical research has been evolved over the years for its effective treatment. However, the advent of chemotherapeutic resistance in breast cancer is one of the major confront researchers are facing in achieving successful chemotherapy. Research in the area of cancer nanotechnology over the years have now been revolutionized through the development of smart polymers, lipids, inorganic materials and eventually their surface-engineering with targeting ligands. Moreover, nanotechnology further extended and brings in the notice the new theranostic approach which combining the therapy and imaging simultaneously. Currently, research is being envisaged in the area of novel nano-pharmaceutical design viz. liposome, nanotubes, polymer lipid hybrid system, which focuses to make the chemotherapy curative and long-lasting. In this review, we aimed to discuss the recent advancement of different surface-engineered/targeted nanomedicines that improved the drug efficacy in breast cancer.
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Affiliation(s)
- Muhammad Afzal
- College of Pharmacy, Jouf University, Al-Jouf, Sakaka, Saudi Arabia
| | - Ameeduzzafar
- College of Pharmacy, Jouf University, Al-Jouf, Sakaka, Saudi Arabia
| | | | | | - Fahad A Al-Abassi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University Jeddah 21589 Saudi Arabia
| | | | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University Jeddah 21589 Saudi Arabia
| | - Vikas Kumar
- Department of Pharmaceutical Sciences, Faculty of Health Sciences, Natural Product Drug Discovery Laboratory, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, India
| | - Mohammad Amjad Kamal
- King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Jeddah 21589, Saudi Arabia; Enzymoics, 7 Peterlee Place, Hebersham, NSW 2770, Australia; Novel Global Community Educational Foundation, Australia
| | - Muhammad Shahid Nadeem
- Department of Biochemistry, Faculty of Science, King Abdulaziz University Jeddah 21589 Saudi Arabia
| | - Muhammad Aslam
- Statistics Department, Faculty of Science, King Abdulaziz University Jeddah 21589 Saudi Arabia
| | - Firoz Anwar
- Department of Biochemistry, Faculty of Science, King Abdulaziz University Jeddah 21589 Saudi Arabia.
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Triptolide-loaded nanoparticles targeting breast cancer in vivo with reduced toxicity. Int J Pharm 2019; 572:118721. [PMID: 31626922 DOI: 10.1016/j.ijpharm.2019.118721] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Revised: 09/10/2019] [Accepted: 09/19/2019] [Indexed: 12/24/2022]
Abstract
Triptolide (TP), a diterpenoid triepoxide that is extracted from the plant Tripterygium wilfordii, has been found to be quite effective for treating many malignant tumors. Although TP was initially considered to be a promising chemotherapeutic agent, its poor solubility and high toxicity limited its potential clinical application. Consequently, we synthesized nanoformulated TP coated with hyaluronic acid (HA) for application in treating breast cancer. Our results showed that TP can prevent tumor progression, but at the cost of significant toxicity. By contrast, using the nanoformulated TP, uptake of drugs into the tumor can be facilitated, which leads to a further increase in efficacy while decreasing systemic toxicity.
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Abo-Zeid MAM, Abo-Elfadl MT, Gamal-Eldeen AM. Evaluation of lapatinib cytotoxicity and genotoxicity on MDA-MB-231 breast cancer cell line. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2019; 71:103207. [PMID: 31234033 DOI: 10.1016/j.etap.2019.103207] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Revised: 05/20/2019] [Accepted: 06/06/2019] [Indexed: 06/09/2023]
Abstract
Lapatinib, one of the tyrosine kinase inhibitors (TKIs), is used to reduce epidermal growth factor family proteins overexpression. This study aims to assess the cytotoxic and genotoxic effects of lapatinib on the triple negative breast cancer cell line "MDA-MB-231". We investigated the cytotoxicity of lapatinib by MTT assay, mode of cell death using apoptosis-necrosis assay, DNA damage using micronucleus test, EGFR protein expression by immunocytochemistry, and assessed its effect on EGFR (7p11.2 locus) and TP53 (17p13 locus) genes using interphase-FISH technique. Lapatinib induced cytotoxicity on MDA-MB-231 cell line by elevating the concentration and its IC50 value was 32.5 μM after 24 h. Lapatinib increased apoptotic cells and micronuclei in binucleated cells gradually by increasing the concentration for 24 h. The EGFR protein expression was reduced by double fold that expressed in non-treated cells. Lapatinib enhanced deletion of EGFR gene signals highly significantly from the lowest concentration. Alternatively, lapatinib amplified signals of TP53 gene effectively by raising the concentration. In conclusion, lapatinib induced cytotoxic and genotoxic effects on MDA-MB-231 cell line. However, laptinib reduced the EGFR protein expression and EGFR signals, it raised the apoptotic cells and TP53 gene signals, which triggered extensive DNA damage. Therefore, lapatinib is an effective TKI in triple negative breast cancer cells as elucidated by its mode of cell death.
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Affiliation(s)
- Mona A M Abo-Zeid
- Genetics and Cytology Department, Genetic Engineering and Biotechnology Research Division, National Research Centre, Dokki, 12622, Cairo, Egypt; Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Dokki, 12622, Cairo, Egypt.
| | - Mahmoud T Abo-Elfadl
- Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Dokki, 12622, Cairo, Egypt; Biochemistry Department, Genetic Engineering and Biotechnology Research Division, National Research Centre, Dokki, 12622, Cairo, Egypt
| | - Amira M Gamal-Eldeen
- Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Dokki, 12622, Cairo, Egypt; Biochemistry Department, Genetic Engineering and Biotechnology Research Division, National Research Centre, Dokki, 12622, Cairo, Egypt; Clinical Laboratory Department, College of Applied Medical Sciences, Taif University, Al Mutamarat Rd, Al Mathnah, At Taif, 26521, Saudi Arabia
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Wang L, You X, Lou Q, He S, Zhang J, Dai C, Zhao M, Zhao M, Hu H, Wu J. Cysteine-based redox-responsive nanoparticles for small-molecule agent delivery. Biomater Sci 2019; 7:4218-4229. [PMID: 31389415 DOI: 10.1039/c9bm00907h] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
As a significant part of molecular-targeted therapies, small-molecule agents (SMAs) have been increasingly used for cancer treatment. Nevertheless, most SMAs are currently administered orally due to their poor solubility, resulting in a low bioavailability and unavoidable side effects. Herein, we proposed a promising SMA delivery strategy using a biocompatible and redox-responsive nanoparticle (NP) delivery system to improve their bioavailability, alleviate side effects and enhance therapeutic performance. To demonstrate the feasibility of this strategy, a type of cysteine-based hydrophobic polymer was employed to construct a redox-sensitive nanoplatform for the delivery of various hydrophobic oral SMAs. These SMA-loaded nanoparticles (SMA-NPs) all have a small particle size and good drug-loading capacity. Particularly, lapatinib-loaded nanoparticles (LAP-NPs) with a minimal particle size (79.71 nm) and an optimal drug-loading capacity (12.5%) were utilized as a model to systemically explore the in vitro and in vivo anticancer potential of SMA-NPs. As expected, the LAP-NPs exhibited rapid redox-responsive drug release, enhanced in vitro cytotoxicity and cell apoptosis, and demonstrated notable anti-metastasis ability and desirable intracellular localization. Additionally, the in vivo results demonstrated the preferential accumulation of LAP-NPs in tumor tissues and the significant suppression of tumor growth. Therefore, the generated SMA-NP delivery system shows great SMA delivery potential for advanced molecular-targeted therapies.
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Affiliation(s)
- Liying Wang
- Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, PR China. and Research Institute of Sun Yat-Sen University in Shenzhen, Shenzhen, 518057, PR China
| | - Xinru You
- Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, PR China.
| | - Qi Lou
- Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University; Shenzhen second people's hospital, Shenzhen, Guangdong, China
| | - Siyu He
- Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, PR China.
| | - Junfu Zhang
- Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, PR China.
| | - Chunlei Dai
- Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, PR China.
| | - Meng Zhao
- Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University; Shenzhen second people's hospital, Shenzhen, Guangdong, China and Shenzhen Lansi Institute of Artificial Intelligence in Medicine, Shenzhen, Guangdong, China
| | - Minyi Zhao
- Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, PR China.
| | - Hai Hu
- SunYat-Sen Memorial Hospital, SunYat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, PR China.
| | - Jun Wu
- Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, PR China. and Research Institute of Sun Yat-Sen University in Shenzhen, Shenzhen, 518057, PR China and SunYat-Sen Memorial Hospital, SunYat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, PR China.
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Sakurai Y, Harashima H. Hyaluronan-modified nanoparticles for tumor-targeting. Expert Opin Drug Deliv 2019; 16:915-936. [DOI: 10.1080/17425247.2019.1645115] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Yu Sakurai
- Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan
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47
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Synergistic triple-combination therapy with hyaluronic acid-shelled PPy/CPT nanoparticles results in tumor regression and prevents tumor recurrence and metastasis in 4T1 breast cancer. Biomaterials 2019; 217:119264. [PMID: 31260883 DOI: 10.1016/j.biomaterials.2019.119264] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 06/06/2019] [Accepted: 06/07/2019] [Indexed: 12/14/2022]
Abstract
Breast cancer is characterized by high aggression, poor prognosis, and high recurrence rate. Early detection and specific targeted treatment with less toxicity are the ultimate goals for breast cancer therapy. To improve antitumor therapeutic effects, we developed a novel polypyrrole nanoparticle using the near infrared dye IRDye800CW with camptothecin (CPT)-conjugated hyaluronic acid (HA) shell (PPy@CPT-HA-IRDye800CW) and performed a photothermal therapy (PTT), along with chemotherapy, guided by fluorescence and photoacoustic dual-modality imaging, in combination with immunotherapy. Irradiation with near infrared (NIR) light offered a strong PTT effect and promoted CPT drug release in tumors. Moreover, we found that chemo-photothermal therapy with PPy@CPT-HA-IRDye800CW NPs, in combination with immune checkpoint inhibitor anti-PD-L1 immunotherapy, synergistically enhanced the anti-tumor immune response, thereby eliminating primary breast cancer and preventing tumor metastases and recurrences in 4T1 tumor-bearing mice. This approach may provide important clues for the clinical management of breast cancer and other malignant tumors.
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48
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Feng C, Zhu D, Chen L, Lu Y, Liu J, Kim NY, Liang S, Zhang X, Lin Y, Ma Y, Dong C. Targeted Delivery of Chlorin e6 via Redox Sensitive Diselenide-Containing Micelles for Improved Photodynamic Therapy in Cluster of Differentiation 44-Overexpressing Breast Cancer. Front Pharmacol 2019; 10:369. [PMID: 31057402 PMCID: PMC6477080 DOI: 10.3389/fphar.2019.00369] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Accepted: 03/25/2019] [Indexed: 12/12/2022] Open
Abstract
The off-target activation of photosensitizers is one of the most well-known obstacles to effective photodynamic therapy (PDT). The selected activation of photosensitizers in cancer cells is highly desired to overcome this problem. We developed a strategy that enabled diselenide bonds to link hyaluronic acid (HA) and photosensitizer chlorin e6 (Ce6) to assemble the micelles (HA-sese-Ce6 NPs) that can target cancer and achieve a redox responsive release of drugs to enhance the PDT efficiency in breast cancer. The HA was used to form a hydrophilic shell that can target cluster of differentiation 44 (CD44) on the cancer cells. The selenium-containing core is easily dissembled in a redox environment to release Ce6. The triggered release of Ce6 in a redox condition and the positive feedback release by activated Ce6 were observed in vitro. In cytotoxicity assays and in vitro cellular uptake assays, the increased PDT efficiency and targeted internalization of HA-sese-Ce6 NPs in the cells were verified, compared to a free Ce6 treated group. Similar results were showed in the therapeutic study and in vivo fluorescence imaging in an orthotopic mammary fat pad tumor model. In addition, a significant inhibition of metastasis was found after the HA-sese-Ce6 NPs treatment. In general, this study promises an ingenious and easy strategy for improved PDT efficiency.
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Affiliation(s)
- Chan Feng
- Cancer Center, Shanghai East Hospital, Tongji University, Shanghai, China
| | - Donglei Zhu
- Cancer Center, Shanghai East Hospital, Tongji University, Shanghai, China
| | - Lv Chen
- Cancer Center, Shanghai East Hospital, Tongji University, Shanghai, China
| | - Yonglin Lu
- Cancer Center, Shanghai East Hospital, Tongji University, Shanghai, China
| | - Jie Liu
- Cancer Center, Shanghai East Hospital, Tongji University, Shanghai, China
| | - Na Yoon Kim
- Department of Chemical Engineering, Northeastern University, Boston, MA, United States
| | - Shujing Liang
- Cancer Center, Shanghai East Hospital, Tongji University, Shanghai, China
| | - Xia Zhang
- Cancer Center, Shanghai East Hospital, Tongji University, Shanghai, China
| | - Yun Lin
- Cancer Center, Shanghai East Hospital, Tongji University, Shanghai, China
| | - Yabin Ma
- Pharmacy Department, Shanghai East Hospital, Tongji University, Shanghai, China
| | - Chunyan Dong
- Cancer Center, Shanghai East Hospital, Tongji University, Shanghai, China
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49
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Preparation, characterisation and in vitro and in vivo evaluation of CD44-targeted chondroitin sulphate-conjugated doxorubicin PLGA nanoparticles. Carbohydr Polym 2019; 213:17-26. [PMID: 30879657 DOI: 10.1016/j.carbpol.2019.02.084] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Revised: 12/25/2018] [Accepted: 02/25/2019] [Indexed: 12/21/2022]
Abstract
The purpose of this study was to ascertain the effect of chondroitin sulphate-modified doxorubicin (Dox) nanoparticles on enhancing the tumour-targeting effect and tumour growth inhibition effect of doxorubicin both in vitro and in vivo. The chondroitin sulphate-doxorubicin conjugate and its poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CS-Dox-PLGA) were successfully synthesised, and then characterized by Fourier-transform infrared spectroscopy (FTIR), proton magnetic resonance (1HNMR), thermogravimetric analysis/differential scanning calorimetry (TGA/DSC), transmission electron microscope (TEM), zeta potential and laser light scattering. Taking advantage of the enhanced permeability and CD44-mediated endocytosis, CS-Dox-PLGA showed excellent capacity for penetrating the peripheral tumour barrier and into the nucleus of tumour cells. The CS-Dox-PLGA cellular uptake was improved and exhibited a significantly higher level of cytotoxicity in U251 cells. After intravenous administration, the CS-Dox-PLGA showed good pharmacokinetic properties and excellent U251-induced tumour inhibition with low cardiac toxicity. Therefore, CS-Dox-PLGA with low cardiac toxicity and good anti-tumour ability might be a better choice for Dox in clinical practice.
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50
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Li H, Li H, Yu W, Huang S, Liu Y, Zhang N, Yuan J, Xu X, Duan S, Hu Y. PEGylated hyaluronidase/NIR induced drug controlled release system for synergetic chemo-photothermal therapy of hepatocellular carcinoma. Eur J Pharm Sci 2019; 133:127-136. [PMID: 30779981 DOI: 10.1016/j.ejps.2019.02.022] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2018] [Revised: 01/26/2019] [Accepted: 02/15/2019] [Indexed: 01/10/2023]
Abstract
In recent years, cancer treatment has been facing the challenge of increasing antitumor efficiency and avoiding severe adverse effects simultaneously. In this study, we designed a controlled release drug delivery system, doxorubicin (Dox)-loaded and hyaluronic acid (HA)-modified PEGylated gold nanocages (AuNCs), which was designated as PEG-HAn-AuNCs/Dox (n represented 10n HA repeating units were modified on each AuNC). In this system, AuNCs were applied as the photothermal cores, Dox was employed as the model drug, HA was applied as the tumor-microenvironment responsive switch to achieve controlled release, and poly (ethylene glycol) (PEG) was used as the stealth polymer to prolong systemic circulation time. Firstly, we evaluated the physical and chemical properties of the PEG-HAn-AuNCs/Dox with different ratios of HA to AuNC and found that PEG-HA4-AuNCs/Dox was the optimal. Secondly, PEG-HA4-AuNCs/Dox revealed the feature of controlled release, namely, the drug release was triggered by hyaluronidase (HAase) and accelerated by the acidic pH and near-infrared (NIR) irradiation. And then PEG-HA4-AuNCs/Dox could be effectively delivered to a cultured SMMC-7721 cell line in vitro and the tumor tissues of the subcutaneous mouse models of hepatocellular carcinoma (HCC) in vivo. Finally, the results demonstrated the synergetic therapy, namely the combination of chemotherapy and photothermal therapy (PTT) (defined as chemo-photothermal therapy) mediated by PEG-HA4-AuNCs/Dox, could efficiently inhibit the tumor growth both in vitro and in vivo. Therefore, the advantages of PEG-HA4-AuNCs/Dox endowed it as a great potential candidate for HCC treatment.
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Affiliation(s)
- Huili Li
- Henan Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China
| | - Huanjie Li
- General Hospital of Xuzhou Mining Group, Quanshan District Coal Road No. 32, Xuzhou, 221006, PR China
| | - Wei Yu
- Henan Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China
| | - Shengnan Huang
- Henan Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China
| | - Ying Liu
- Henan Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China
| | - Ningxia Zhang
- Henan Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China
| | - Jinxiu Yuan
- Henan Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China
| | - Xin Xu
- Henan Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China
| | - Shaofeng Duan
- Institute for Innovative Drug Design and Evaluation, School of Pharmacy, Henan University, N. Jinming Ave., Kaifeng, Henan 475004, PR China; Henan International Joint Laboratory for Nuclear Protein Regulation, School of Medical Sciences, Henan University, N. Jinming Ave., Kaifeng, Henan 475004, PR China.
| | - Yurong Hu
- Henan Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China; Key Laboratory of Key Technology of Drug Preparation, Ministry of Education, Institute of Drug Discovery & Development, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China.
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