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Meng X, Tian L, Zhang J, Wang J, Cao X, Hu Z, Sun Y, Dai Z, Zheng X. Tumor microenvironment-regulated nanoplatform for enhanced chemotherapy, cuproptosis and nonferrous ferroptosis combined cancer therapy. J Mater Chem B 2025; 13:1089-1099. [PMID: 39652201 DOI: 10.1039/d4tb02000f] [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: 01/16/2025]
Abstract
Therapeutic approaches combining various treatments have attracted intensive interests for tumor therapy. Nevertheless, these strategies still face many obstacles, such as overexpressed GSH and hypoxia, owing to the intricate tumor microenvironment (TME). Herein, a versatile nanoplatform, CeO2@CuO2@DOX-RSL3@HA (CCDRH), was initially constructed for promoting the antitumor efficiency via regulation of the TME. The CCDRH was prepared taking mixed valence CeO2 as the nanocarrier, followed by the attachment of CuO2 nanodots, DOX and RSL3 and the camouflaging of hyaluronic acid. The CuO2 could disassemble in the acidic TME to release Cu2+ and H2O2. The POD- and CAT-mimicking activities of CeO2 could convert H2O2 to ˙OH and O2, leading to the enhancement of chemo-chemodynamic therapy. Meanwhile, RSL3 could effectively suppress GPX4 expression, and the overloaded Cu2+ and Ce4+ could deplete excess GSH, resulting in an intensive accumulation of LPO and significant nonferrous ferroptosis. Additionally, Cu+ induces the oligomerization of lipoylated DLAT and downregulates iron-sulfur cluster proteins, resulting in potent cellular cuproptosis. The experimental results revealed that CCDRH exhibited high performance in tumor inhibition, which is attributed to the combined effect of enhanced chemotherapy, ferroptosis and cuproptosis. The study provides a new approach for improving anticancer efficiency via regulation of the TME.
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Affiliation(s)
- Xiangyu Meng
- College of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, P. R. China.
- Qilu Normal University, Jinan 250000, P. R. China.
- Key Laboratory of Advanced Biomaterials and Nanomedicine in Universities of Shandong, Linyi University, Linyi 276000, P. R. China
| | - Lu Tian
- College of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, P. R. China.
- Key Laboratory of Advanced Biomaterials and Nanomedicine in Universities of Shandong, Linyi University, Linyi 276000, P. R. China
| | - Jingmei Zhang
- School of Chemical Engineering, Hebei Normal University of Science and Technology, Qinhuangdao 066000, P. R. China
| | - Jiaoyu Wang
- College of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, P. R. China.
- Qilu Normal University, Jinan 250000, P. R. China.
- Key Laboratory of Advanced Biomaterials and Nanomedicine in Universities of Shandong, Linyi University, Linyi 276000, P. R. China
| | - Xuewei Cao
- Qilu Normal University, Jinan 250000, P. R. China.
- Key Laboratory of Advanced Biomaterials and Nanomedicine in Universities of Shandong, Linyi University, Linyi 276000, P. R. China
- College of Medicine, Linyi University, Linyi 276000, P. R. China
| | - Zunfu Hu
- Key Laboratory of Advanced Biomaterials and Nanomedicine in Universities of Shandong, Linyi University, Linyi 276000, P. R. China
| | - Yunqiang Sun
- College of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, P. R. China.
| | - Zhichao Dai
- College of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, P. R. China.
- Key Laboratory of Advanced Biomaterials and Nanomedicine in Universities of Shandong, Linyi University, Linyi 276000, P. R. China
| | - Xiuwen Zheng
- Qilu Normal University, Jinan 250000, P. R. China.
- Key Laboratory of Advanced Biomaterials and Nanomedicine in Universities of Shandong, Linyi University, Linyi 276000, P. R. China
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2
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Süngü Akdoğan Ç, Akbay Çetin E, Onur MA, Önel S, Tuncel A. Copper(II) Oxide Spindle-like Nanomotors Decorated with Calcium Peroxide Nanoshell as a New Nanozyme with Photothermal and Chemodynamic Functions Providing ROS Self-Amplification, Glutathione Depletion, and Cu(I)/Cu(II) Recycling. ACS APPLIED MATERIALS & INTERFACES 2025; 17:632-649. [PMID: 39720911 PMCID: PMC11783533 DOI: 10.1021/acsami.4c17852] [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: 10/16/2024] [Revised: 12/10/2024] [Accepted: 12/10/2024] [Indexed: 12/26/2024]
Abstract
Uniform, mesoporous copper(II) oxide nanospindles (CuO NSs) were synthesized via a method based on templated hydrothermal oxidation of copper in the presence of monodisperse poly(glycerol dimethacrylate-co-methacrylic acid) nanoparticles (poly(GDMA-co-MAA) NPs). Subsequent decoration of CuO NSs with a CaO2 nanoshell (CuO@CaO2 NSs) yielded a nanozyme capable of Cu(I)/Cu(II) redox cycling. Activation of the Cu(I)/Cu(II) cycle by exogenously generated H2O2 from the CaO2 nanoshell significantly enhanced glutathione (GSH) depletion. CuO@CaO2 NSs exhibited a 2-fold higher GSH depletion rate compared to pristine CuO NSs. The generation of oxygen due to the catalase (CAT)-like decomposition of H2O2 by CuO@CaO2 NSs resulted in a self-propelled diffusion behavior, characteristic of a H2O2 fueled nanomotor. These nanostructures exhibited both peroxidase (POD)-like and CAT-like activities and were capable of self-production of H2O2 in aqueous media via a chemical reaction between the CaO2 nanoshell and water. Usage of the self-supplied H2O2 by the POD-like activity of CuO@CaO2 NSs amplified the generation of toxic hydroxyl (•OH) radicals, enhancing the chemodynamic effect within the tumor microenvironment (TME). The CAT-like activity provided a source of self-supplied O2 via decomposition of H2O2 to alleviate hypoxic conditions in the TME. Under near-infrared laser irradiation, CuO@CaO2 NSs exhibited photothermal conversion properties, with a temperature elevation of 25 °C. The combined GSH depletion and H2O2 generation led to a more effective production of •OH radicals in the cell culture medium. The chemodynamic function was further enhanced by an elevated temperature. To assess the therapeutic potential, CuO@CaO2 NSs loaded with the photosensitizer, chlorine e6 (Ce6), were evaluated against T98G glioblastoma cells. The synergistic combination of photodynamic, photohermal, and chemodynamic modalities using CuO@CaO2@Ce6 NSs resulted in cell death higher than 90% under in vitro conditions.
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Affiliation(s)
- Çağıl
Zeynep Süngü Akdoğan
- Bioengineering
Division, Hacettepe University, Ankara 06800, Turkey
- Graduate
School of Science & Engineering, Hacettepe
University, Ankara 06800, Turkey
| | - Esin Akbay Çetin
- Department
of Biology, Hacettepe University, Ankara 06800, Turkey
| | - Mehmet Ali Onur
- Bioengineering
Division, Hacettepe University, Ankara 06800, Turkey
- Department
of Biology, Hacettepe University, Ankara 06800, Turkey
| | - Selis Önel
- Bioengineering
Division, Hacettepe University, Ankara 06800, Turkey
- Chemical
Engineering Department, Hacettepe University, Ankara 06800, Turkey
| | - Ali Tuncel
- Bioengineering
Division, Hacettepe University, Ankara 06800, Turkey
- Chemical
Engineering Department, Hacettepe University, Ankara 06800, Turkey
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3
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Ren L, Zhang J, Nie L, Shavandi A, Yunusov KE, Aharodnikau UE, Solomevich SO, Sun Y, Jiang G. Platelet Membrane-Camouflaged Copper Doped CaO 2 Biomimetic Nanomedicines for Breast Cancer Combination Treatment. ACS Biomater Sci Eng 2024; 10:7492-7506. [PMID: 39491550 DOI: 10.1021/acsbiomaterials.4c01362] [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: 11/05/2024]
Abstract
Breast cancer (BC) is the most frequently diagnosed cancer in women worldwide. Chemodynamic therapy (CDT), photothermal therapy (PTT), and ion interference therapy (IIT), used in combination, represent a common treatment. In this study, platelet membrane-camouflaged copper-doped CaO2 biomimetic nanomedicines have been developed for breast cancer treatments. Copper-doped CaO2 nanoparticles were first coated by polydopamine (PDA) and subsequently camouflaged by platelet membrane (PM) to form platelet membrane-camouflaged copper doped CaO2 biomimetic nanomedicines (Cu-CaO2@PDA/PM). The as-fabricated Cu-CaO2@PDA/PM multifunctional nanomedicines could decompose within the tumor microenvironment to release Ca2+ for ion interference therapy, and the generated H2O2 could perform a Fenton-like reaction with the assistance of loaded copper ions to produce ·OH, thus realizing chemodynamic therapy. In addition, the copper ions could also consume glutathione and weaken its ability to scavenge reactive oxygen species, which was conducive to amplifying the effect of oxidative stress. The coating of the polydopamine layer could achieve local hyperthermia of the tumor site, and the surface modification of the platelet membrane could enhance the targeting and biocompatibility of nanomedicines. In vivo and in vitro tests demonstrated that the developed Cu-CaO2@PDA/PM biomimetic nanomedicines offer a promising biomimetic nanoplatform for efficient multimodal combination therapy for breast cancer.
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Affiliation(s)
- Luping Ren
- School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou, 310018, China
- International Scientific and Technological Cooperation Base of Intelligent Biomaterials and Functional Fibers of Zhejiang Province, Hangzhou, 310018, China
| | - Junhao Zhang
- School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou, 310018, China
- International Scientific and Technological Cooperation Base of Intelligent Biomaterials and Functional Fibers of Zhejiang Province, Hangzhou, 310018, China
| | - Lei Nie
- College of Life Sciences, Xinyang Normal University, Xinyang 464000, China
| | - Armin Shavandi
- Université libre de Bruxelles (ULB), École Polytechnique de Bruxelles, 3BIO10 BioMatter, Avenue F.D. Roosevelt, 50 - CP 165/61, 1050 Brussels, Belgium
| | - Khaydar E Yunusov
- Institute of Polymer Chemistry and Physics, Uzbekistan Academy of Sciences, Tashkent, 100128, Uzbekistan
| | - Uladzislau E Aharodnikau
- Research Institute for Physical Chemical Problems of the Belarusian State University, Minsk 220030, Belarus
| | - Sergey O Solomevich
- Research Institute for Physical Chemical Problems of the Belarusian State University, Minsk 220030, Belarus
| | - Yanfang Sun
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018, China
| | - Guohua Jiang
- School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou, 310018, China
- International Scientific and Technological Cooperation Base of Intelligent Biomaterials and Functional Fibers of Zhejiang Province, Hangzhou, 310018, China
- Zhejiang-Mauritius Joint Research Center for Biomaterials and Tissue Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, P. R. China
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Wu S, Gao M, Chen L, Wang Y, Zheng X, Zhang B, Li J, Zhang XD, Dai R, Zheng Z, Zhang R. A Multifunctional Nanoreactor-Induced Dual Inhibition of HSP70 Strategy for Enhancing Mild Photothermal/Chemodynamic Synergistic Tumor Therapy. Adv Healthc Mater 2024; 13:e2400819. [PMID: 38722289 DOI: 10.1002/adhm.202400819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Revised: 04/29/2024] [Indexed: 05/18/2024]
Abstract
Mild photothermal therapy (PTT) is a spatiotemporally controllable method that utilizes the photothermal effect at relatively low temperatures (40-45 °C) to especially eliminate tumor tissues with negligible side effects on the surrounding normal tissues. However, the overexpression of heat shock protein 70 (HSP70) and limited effect of single treatment drastically impede the therapeutic efficacy. Herein, the constructed multifunctional core-shell structured Ag-Cu@SiO2-PDA/GOx nanoreactors (APG NRs) that provide a dual inhibition of HSP70 strategy for the second near-infrared photoacoustic (NIR-II PA) imaging-guided combined mild PTT/chemodynamic therapy (CDT). The Ag-Cu cores can convert endogenous H2O2 to hydroxyl radical (•OH), which can induce lipid peroxidation (LPO) and further degrade HSP70. The polydopamine (PDA)/glucose oxidase (GOx) shells are utilized as the NIR-II photothermal agent to generate low temperature, and the GOx can reduce the energy supplies and inhibit energy-dependent HSP70 expression. Furthermore, both the generation of •OH and GOx-mediated energy shortage can reduce HSP70 expression to sensitize mild PTT under 1064 nm laser, and in turn, GOx and laser self-amplify the catalytic reactions of APG NRs for more production of •OH. The multifunctional nanoreactors will provide more potential possibilities for the clinical employment of mild PTT and the advancement of tumor combination therapies.
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Affiliation(s)
- Shutong Wu
- Laboratory of Molecular Imaging, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People's Hospital), Taiyuan, 030000, China
- The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Mengting Gao
- The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Lin Chen
- Laboratory of Molecular Imaging, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People's Hospital), Taiyuan, 030000, China
| | - Yuhang Wang
- Laboratory of Molecular Imaging, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People's Hospital), Taiyuan, 030000, China
- The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Xiaochun Zheng
- Laboratory of Molecular Imaging, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People's Hospital), Taiyuan, 030000, China
- The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Binyue Zhang
- Laboratory of Molecular Imaging, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People's Hospital), Taiyuan, 030000, China
| | - Juan Li
- Laboratory of Molecular Imaging, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People's Hospital), Taiyuan, 030000, China
| | - Xiao-Dong Zhang
- Department of Physics and Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, School of Sciences, Tianjin University, Tianjin, 300350, China
| | - Rong Dai
- Laboratory of Molecular Imaging, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People's Hospital), Taiyuan, 030000, China
- The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Ziliang Zheng
- Laboratory of Molecular Imaging, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People's Hospital), Taiyuan, 030000, China
- The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Ruiping Zhang
- Laboratory of Molecular Imaging, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People's Hospital), Taiyuan, 030000, China
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5
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Zhang X, Li M, Tang YL, Zheng M, Liang XH. Advances in H 2O 2-supplying materials for tumor therapy: synthesis, classification, mechanisms, and applications. Biomater Sci 2024; 12:4083-4102. [PMID: 39010783 DOI: 10.1039/d4bm00366g] [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: 07/17/2024]
Abstract
Hydrogen peroxide (H2O2) as a reactive oxygen species produced by cellular metabolism can be used in antitumor therapy. However, the concentration of intracellular H2O2 limits its application. Some materials could enhance the concentration of intracellular H2O2 to strengthen antitumor therapy. In this review, the recent advances in H2O2-supplying materials in terms of promoting intracellular H2O2 production and exogenous H2O2 supply are summarized. Then the mechanism of H2O2-supplying materials for tumor therapy is discussed from three aspects: reconstruction of the tumor hypoxia microenvironment, enhancement of oxidative stress, and the intrinsic anti-tumor ability of H2O2-supplying materials. In addition, the application of H2O2-supplying materials for tumor therapy is discussed. Finally, the future of H2O2-supplying materials is presented. This review aims to provide a novel idea for the application of H2O2-supplying materials in tumor therapy.
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Affiliation(s)
- Xu Zhang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, No. 14, Sec. 3, Renminnan Road, Chengdu, Sichuan 610041, People's Republic of China.
| | - Mao Li
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, No.14, Sec. 3, Renminnan Road, Chengdu, Sichuan 610041, People's Republic of China
| | - Ya-Ling Tang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, No.14, Sec. 3, Renminnan Road, Chengdu, Sichuan 610041, People's Republic of China
| | - Min Zheng
- Department of Stomatology, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, Zhejiang, China.
| | - Xin-Hua Liang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, No. 14, Sec. 3, Renminnan Road, Chengdu, Sichuan 610041, People's Republic of China.
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Li Y, Wang J, Zhu T, Zhan Y, Tang X, Xi J, Zhu X, Zhang Y, Liu J. A ROS storm generating nanocomposite for enhanced chemodynamic therapy through H 2O 2 self-supply, GSH depletion and calcium overload. NANOSCALE 2024; 16:8479-8494. [PMID: 38590261 DOI: 10.1039/d3nr06422k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/10/2024]
Abstract
Catalytic generation of toxic hydroxyl radicals (˙OH) from hydrogen peroxide (H2O2) is an effective strategy for tumor treatment in chemodynamic therapy (CDT). However, the intrinsic features of the microenvironment in solid tumors, characterized by limited H2O2 and overexpressed glutathione (GSH), severely impede the accumulation of intracellular ˙OH, posing significant challenges. To circumvent these critical issues, in this work, a CaO2-based multifunctional nanocomposite with a surface coating of Cu2+ and L-buthionine sulfoximine (BSO) (named CaO2@Cu-BSO) is designed for enhanced CDT. Taking advantage of the weakly acidic environment of the tumor, the nanocomposite gradually disintegrates, and the exposed CaO2 nanoparticles subsequently decompose to produce H2O2, alleviating the insufficient supply of endogenous H2O2 in the tumor microenvironment (TME). Furthermore, Cu2+ detached from the surface of CaO2 is reduced by H2O2 and GSH to Cu+ and ROS. Then, Cu+ catalyzes H2O2 to generate highly cytotoxic ˙OH and Cu2+, forming a cyclic catalysis effect for effective CDT. Meanwhile, GSH is depleted by Cu2+ ions to eliminate possible ˙OH scavenging. In addition, the decomposition of CaO2 by TME releases a large amount of free Ca2+, resulting in the accumulation and overload of Ca2+ and mitochondrial damage in tumor cells, further improving CDT efficacy and accelerating tumor apoptosis. Besides, BSO, a molecular inhibitor, decreases GSH production by blocking γ-glutamyl cysteine synthetase. Together, this strategy allows for enhanced CDT efficiency via a ROS storm generation strategy in tumor therapy. The experimental results confirm and demonstrate the satisfactory tumor inhibition effect both in vitro and in vivo.
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Affiliation(s)
- Yong Li
- School of Environmental and Chemical Engineering, Shanghai University, Shanghai, China, 200444.
| | - Jing Wang
- School of Environmental and Chemical Engineering, Shanghai University, Shanghai, China, 200444.
| | - Tao Zhu
- School of Environmental and Chemical Engineering, Shanghai University, Shanghai, China, 200444.
| | - Ying Zhan
- School of Life Science, Shanghai University, Shanghai, China, 200444
| | - Xiaoli Tang
- School of Environmental and Chemical Engineering, Shanghai University, Shanghai, China, 200444.
| | - Jianying Xi
- School of Environmental and Chemical Engineering, Shanghai University, Shanghai, China, 200444.
| | - Xiaohui Zhu
- School of Environmental and Chemical Engineering, Shanghai University, Shanghai, China, 200444.
| | - Yong Zhang
- Department of Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong.
| | - Jinliang Liu
- School of Environmental and Chemical Engineering, Shanghai University, Shanghai, China, 200444.
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Ren L, Sun Y, Zhang J, Nie L, Shavandi A, Yunusov KE, Aharodnikau UE, Solomevich SO, Jiang G. Red blood cell membrane-coated functionalized Cu-doped metal organic framework nanoformulations as a biomimetic platform for improved chemo-/chemodynamic/photothermal synergistic therapy. Int J Pharm 2024; 652:123811. [PMID: 38237709 DOI: 10.1016/j.ijpharm.2024.123811] [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: 09/28/2023] [Revised: 12/27/2023] [Accepted: 01/12/2024] [Indexed: 01/27/2024]
Abstract
Nanoformulations for combining chemotherapy, chemodynamic therapy, and photothermal therapy have enormous potential in tumor treatment. Coating nanoformulations with cell membranes endows them with homologous cellular mimicry, enabling nanoformulations to acquire new functions and properties, including homologous targeting and long circulation in vivo, and can enhance internalization by homologous cancer cells. Herein, we fused multifunctional biomimetic nanoformulations based on Cu-doped zeolitic imidazolate framework-8 (ZIF-8). Hydroxycamptothecin (HCPT), a clinical anti-tumor drug, was encapsulated into ZIF-8, which was subsequently coated with polydopamine (PDA) and red blood cell membrane. The as-fabricated biomimetic nanoformulations showed an enhanced cell uptake in vitro and the potential to prolong blood circulation in vivo, producing effective synergistic chemotherapy, chemodynamic therapy, and photothermal therapy under the 808 nm laser irradiation. Together, the biomimetic nanoformulations showed a prolonged blood circulation and evasion of immune recognition in vivo to provide a bio-inspired strategy which may have the potential for the multi-synergistic therapy of breast cancer.
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Affiliation(s)
- Luping Ren
- School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou, 310018, China; International Scientific and Technological Cooperation Base of Intelligent Biomaterials and Functional Fibers of Zhejiang Province, Hangzhou 310018, China
| | - Yanfang Sun
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou Zhejiang, 310018, China.
| | - Junhao Zhang
- School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou, 310018, China; International Scientific and Technological Cooperation Base of Intelligent Biomaterials and Functional Fibers of Zhejiang Province, Hangzhou 310018, China
| | - Lei Nie
- College of Life Sciences, Xinyang Normal University, Xinyang 464000, China
| | - Amin Shavandi
- Université libre de Bruxelles (ULB), École polytechnique de Bruxelles, 3BIO10 BioMatter, Avenue F.D. Roosevelt, 50 - CP 165/61, 1050 Brussels, Belgium
| | - Khaydar E Yunusov
- Institute of Polymer Chemistry and Physics, Uzbekistan Academy of Sciences, Tashkent, 100128, Uzbekistan
| | - Uladzislau E Aharodnikau
- Research Institute for Physical Chemical Problems of the Belarusian State University, Minsk, 220030, Belarus
| | - Sergey O Solomevich
- Research Institute for Physical Chemical Problems of the Belarusian State University, Minsk, 220030, Belarus
| | - Guohua Jiang
- School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou, 310018, China; International Scientific and Technological Cooperation Base of Intelligent Biomaterials and Functional Fibers of Zhejiang Province, Hangzhou 310018, China.
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8
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Feng Y, Wang J, Cao J, Cao F, Chen X. Manipulating calcium homeostasis with nanoplatforms for enhanced cancer therapy. EXPLORATION (BEIJING, CHINA) 2024; 4:20230019. [PMID: 38854493 PMCID: PMC10867402 DOI: 10.1002/exp.20230019] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 08/28/2023] [Indexed: 06/11/2024]
Abstract
Calcium ions (Ca2+) are indispensable and versatile metal ions that play a pivotal role in regulating cell metabolism, encompassing cell survival, proliferation, migration, and gene expression. Aberrant Ca2+ levels are frequently linked to cell dysfunction and a variety of pathological conditions. Therefore, it is essential to maintain Ca2+ homeostasis to coordinate body function. Disrupting the balance of Ca2+ levels has emerged as a potential therapeutic strategy for various diseases, and there has been extensive research on integrating this approach into nanoplatforms. In this review, the current nanoplatforms that regulate Ca2+ homeostasis for cancer therapy are first discussed, including both direct and indirect approaches to manage Ca2+ overload or inhibit Ca2+ signalling. Then, the applications of these nanoplatforms in targeting different cells to regulate their Ca2+ homeostasis for achieving therapeutic effects in cancer treatment are systematically introduced, including tumour cells and immune cells. Finally, perspectives on the further development of nanoplatforms for regulating Ca2+ homeostasis, identifying scientific limitations and future directions for exploitation are offered.
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Affiliation(s)
- Yanlin Feng
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of PhysiologyShanxi Medical UniversityTaiyuanChina
| | - Jianlin Wang
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of PhysiologyShanxi Medical UniversityTaiyuanChina
| | - Jimin Cao
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of PhysiologyShanxi Medical UniversityTaiyuanChina
| | - Fangfang Cao
- Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingaporeSingapore
- Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
| | - Xiaoyuan Chen
- Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingaporeSingapore
- Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
- Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
- Agency for Science, Technology, and Research (A*STAR)Institute of Molecular and Cell BiologySingaporeSingapore
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Awaad A, Olama ZA, El-Subruiti GM, Ali SM. The dual activity of CaONPs as a cancer treatment substance and at the same time resistance to harmful microbes. Sci Rep 2023; 13:22940. [PMID: 38135693 PMCID: PMC10746744 DOI: 10.1038/s41598-023-49637-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 12/10/2023] [Indexed: 12/24/2023] Open
Abstract
Nanotechnology holds significant promise for the development of novel and necessary products that enhance human health. Pharmacology and nanotechnology have contributed to developing advanced and highly effective drugs for cancer treatment and combating microbial infections. The microbiological effectiveness against the variety of examined microorganisms was assessed using the time killer curve, scanning electron microscopy (SEM), MIC techniques, and the agar well diffusion method. SEM was utilized to enhance the analysis of the mechanisms underlying the bio-interface interaction and intracellular localization of calcium oxide nanoparticles (CaONPs). The MTT test was used to examine the cytotoxicity of CaONP anticancer activity in various cancer cells, including colon, breast, and hepatic cells. The efficacy of CaONPs as an anticancer medication was elucidated by analyzing the gene expression of both treated and untreated cancer cells. MIC and MBC of CaONPs against Escherichia coli and Staphylococcus epidermidis were 150, 150, 150, and 200 µg/ml, respectively. The MIC and MFC of CaONPs against Candida albicans were 200 µg/ml and 250 µg/ml, respectively. The IC50 values of various CaONPs vary depending on the type of cancer cells. The gene expression analysis of breast cancer cells undergoing treatment revealed the identification of several cancer-controlling genes, namely BAX, BCL2, P53, TERT, KRAS1, KRAS2, and RB1. The study demonstrated the notable antibacterial efficacy of CaONPs, highlighting their potential as cancer therapies.
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Affiliation(s)
- Amr Awaad
- Department of Botany and Microbiology, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Zakia A Olama
- Department of Botany and Microbiology, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Gehan M El-Subruiti
- Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Safaa M Ali
- Nucleic Acid Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications, New Borg El-Arab City, 21934, Alexandria, Egypt.
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10
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Chen MN, Fang ZX, Wu Z, Bai JW, Li RH, Wen XF, Zhang GJ, Liu J. Notch3 restricts metastasis of breast cancers through regulation of the JAK/STAT5A signaling pathway. BMC Cancer 2023; 23:1257. [PMID: 38124049 PMCID: PMC10734157 DOI: 10.1186/s12885-023-11746-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 12/12/2023] [Indexed: 12/23/2023] Open
Abstract
PURPOSE To explore the potential role of signal transducer and activator of transcription 5A (STAT5A) in the metastasis of breast cancer, and its mechanism of regulation underlying. METHODS AND RESULTS TCGA datasets were used to evaluate the expression of STAT5A in normal and different cancerous tissues through TIMER2.0, indicating that STAT5A level was decreased in breast cancer tissues compared with normal ones. Gene Set Enrichment Analysis predicted that STAT5A was associated with the activation of immune cells and cell cycle process. We further demonstrated that the infiltration of immune cells was positively associated with STAT5A level. Influorescence staining revealed the expression and distribution of F-actin was regulated by STAT5A, while colony formation assay, wound healing and transwell assays predicted the inhibitory role of STAT5A in the colony formation, migratory and invasive abilities in breast cancer cells. In addition, overexpression of the Notch3 intracellular domain (N3ICD), the active form of Notch3, resulted in the increased expression of STAT5A. Conversely, silencing of Notch3 expression by siNotch3 decreased STAT5A expression, supporting that STAT5A expression is positively associated with Notch3 in human breast cancer cell lines and breast cancer tissues. Mechanistically, chromatin immunoprecipitation showed that Notch3 was directly bound to the STAT5A promoter and induced the expression of STAT5A. Moreover, overexpressing STAT5A partially reversed the enhanced mobility of breast cancer cells following Notch3 silencing. Low expression of Notch3 and STAT5A predicted poorer prognosis of patients with breast cancer. CONCLUSION The present study demonstrates that Notch3 inhibits metastasis in breast cancer through inducing transcriptionally STAT5A, which was associated with tumor-infiltrating immune cells, providing a novel strategy to treat breast cancer.
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Affiliation(s)
- Min-Na Chen
- Department of Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Ze-Xuan Fang
- The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Zheng Wu
- The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Jing-Wen Bai
- Department of Medical Oncology/Xiamen Key Laboratory for Endocrine-Related Cancer Precision Medicine, Xiamen University Medical School, Xiang'an Hospital of Xiamen University, Xiamen, China
| | - Rong-Hui Li
- Department of Medical Oncology/Xiamen Key Laboratory for Endocrine-Related Cancer Precision Medicine, Xiamen University Medical School, Xiang'an Hospital of Xiamen University, Xiamen, China
| | - Xiao-Fen Wen
- Department of Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Guo-Jun Zhang
- Xiamen Key Laboratory for Endocrine-Related Cancer Precision Medicine/Department of Breast and Thyroid Surgery, Xiamen University Medical School, Xiang'an Hospital of Xiamen University, Xiamen, China.
| | - Jing Liu
- The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, China.
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11
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He C, Zhang S, Liu X, Wang J, Huang Y, Zhang A, Zhang X. CaO 2nanomedicines: a review of their emerging roles in cancer therapy. NANOTECHNOLOGY 2023; 34:482002. [PMID: 37619542 DOI: 10.1088/1361-6528/acf381] [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: 05/27/2023] [Accepted: 08/23/2023] [Indexed: 08/26/2023]
Abstract
Metal peroxide-based nanomedicines have emerged as promising theranostic agents for cancer due to their multifunctional properties, including the generation of bioactive small molecules such as metal ions, H2O2, O2, and OH-. Among these metal peroxides, calcium peroxide (CaO2) nanomedicines have attracted significant attention due to their facile synthesis and good biocompatibility. CaO2nanoparticles have been explored for cancer treatment through three main mechanisms: (1) the release of O2, which helps alleviate tumor hypoxia and enhances oxygen-dependent therapies such as chemotherapy, photodynamic therapy, and immunotherapy; (2) the generation of H2O2, a precursor for ·OH generation, which enables cancer chemodynamic therapy; and (3) the release of Ca2+ions, which induce calcium overload and promote cell apoptosis (called ion-interference therapy). This review provides a comprehensive summary of recent examples of CaO2nanoparticle-based cancer therapeutic strategies, as well as discusses the challenges and future directions in the development of CaO2nanomedicines for cancer treatment.
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Affiliation(s)
- Chuanchuan He
- Jiaxing Maternity and Child Health Care Hospital, Affiliated Women and Children Hospital, Jiaxing University, Jiaxing, Zhejiang, People's Republic of China
| | - Shasha Zhang
- Wuhan Wuchang Hospital, Wuchang Hospital Affiliated to Wuhan University of Science and Technology, People's Republic of China
| | - Xiaoguang Liu
- College of Pharmacy and Life Science, Jiujiang University, Jiujiang, 332005, People's Republic of China
| | - Jianguo Wang
- Jiaxing Maternity and Child Health Care Hospital, Affiliated Women and Children Hospital, Jiaxing University, Jiaxing, Zhejiang, People's Republic of China
| | - Yimin Huang
- Jiaxing Maternity and Child Health Care Hospital, Affiliated Women and Children Hospital, Jiaxing University, Jiaxing, Zhejiang, People's Republic of China
| | - Anxin Zhang
- Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiahang Road 118, Jiaxing 314001, People's Republic of China
| | - Xiaojuan Zhang
- Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiahang Road 118, Jiaxing 314001, People's Republic of China
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12
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Wang W, Yu J, Lin Y, Li M, Pan Y, He Y, Liu L, Meng X, Lv Z, Jin K, Che S, Mou X, Cai Y. NIR absorptive croconic acid/quercetin/CaO2 nanoplatform for tumor calcium overload therapy combined mild photothermal therapy. BIOMATERIALS ADVANCES 2023; 149:213418. [PMID: 37062124 DOI: 10.1016/j.bioadv.2023.213418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 03/14/2023] [Accepted: 03/31/2023] [Indexed: 04/05/2023]
Abstract
With excellent biocompatibility, stable chemical and optical properties, small organic molecules-based agents have always been a research hotspot in cancer photothermal therapy (PTT). In this work, a novel croconic acid-based molecule (CR) was designed and synthesized as an ideal photothermal agent (PTA), which showed abundant near-infrared (NIR) light absorption, high photothermal conversion ability, and excellent photothermal stability. By loading CR and quercetin (Qu) in CaO2, and coated with DSPE-PEG2000, a multifunctional theranostic nanoparticle (CCQ) was successfully prepared for calcium overloading mitochondrial metabolism inhibition synergetic mild PTT. Upon entering tumor microenvironment, CCQ can produce abundant H2O2 and a large amount of calcium ions, which lead to the imbalance of calcium concentration in the internal environment of tumor cells and induced mitochondrial apoptosis. With the existence of Qu, CCQ can effectively inhibit the expression of heat shock proteins (Hsp) during the PTT process, which weaken the heat resistance of tumors, ablate tumors at lower temperature (~45 °C), and reduce the damage to normal tissues. Guided by photoacoustic imaging (PAI), CCQ showed excellent multimodal therapeutic effect of tumors. This study provided a novel CR organic molecule-based theranostic nanoplatform that can be used to treat tumors via calcium overload therapy synergetic PTT at safe temperatures, which has promising potential for the future clinical cancer treatment.
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Affiliation(s)
- Wenliang Wang
- College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, China; Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Jing Yu
- College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, China
| | - Yan Lin
- Department of Gastroenterology, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Meng Li
- College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, China; Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Yi Pan
- Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Yichen He
- Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Longcai Liu
- Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Xuli Meng
- General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
| | - Zhenye Lv
- General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
| | - Ketao Jin
- Department of Colorectal Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang 321000, China.
| | - Shenglei Che
- College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, China
| | - Xiaozhou Mou
- Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
| | - Yu Cai
- Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
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Khannanov A, Burmatova A, Ignatyeva K, Vagizov F, Kiiamov A, Tayurskii D, Cherosov M, Gerasimov A, Vladimir E, Kutyreva M. Effect of the Synthetic Approach on the Formation and Magnetic Properties of Iron-Based Nanophase in Branched Polyester Polyol Matrix. Int J Mol Sci 2022; 23:ijms232314764. [PMID: 36499092 PMCID: PMC9735957 DOI: 10.3390/ijms232314764] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 11/15/2022] [Accepted: 11/22/2022] [Indexed: 11/29/2022] Open
Abstract
This article shows the success of using the chemical reduction method, the polyol thermolytic process, the sonochemistry method, and the hybrid sonochemistry/polyol process method to design iron-based magnetically active composite nanomaterials in a hyperbranched polyester polyol matrix. Four samples were obtained and characterized by transmission and scanning electron microscopy, infrared spectroscopy and thermogravimetry. In all cases, the hyperbranched polymer is an excellent stabilizer of the iron and iron oxides nanophase. In addition, during the thermolytic process and hybrid method, the branched polyol exhibits the properties of a good reducing agent. The use of various approaches to the synthesis of iron nanoparticles in a branched polyester polyol matrix makes it possible to control the composition, geometry, dispersity, and size of the iron-based nanophase and to create new promising materials with colloidal stability, low hemolytic activity, and good magnetic properties. The NMR relaxation method proved the possibility of using the obtained composites as tomographic probes.
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Affiliation(s)
- Artur Khannanov
- Butlerov Chemistry Institute, Kazan Federal University, 420008 Kazan, Russia
| | - Anastasia Burmatova
- Butlerov Chemistry Institute, Kazan Federal University, 420008 Kazan, Russia
| | - Klara Ignatyeva
- Butlerov Chemistry Institute, Kazan Federal University, 420008 Kazan, Russia
| | - Farit Vagizov
- Institute of Physics, Kazan Federal University, 420008 Kazan, Russia
| | - Airat Kiiamov
- Institute of Physics, Kazan Federal University, 420008 Kazan, Russia
- Correspondence:
| | - Dmitrii Tayurskii
- Institute of Physics, Kazan Federal University, 420008 Kazan, Russia
| | - Mikhail Cherosov
- Institute of Physics, Kazan Federal University, 420008 Kazan, Russia
| | - Alexander Gerasimov
- Butlerov Chemistry Institute, Kazan Federal University, 420008 Kazan, Russia
| | - Evtugyn Vladimir
- Interdisciplinary Center “Analytical Microscopy”, Kazan Federal University, 420008 Kazan, Russia
| | - Marianna Kutyreva
- Butlerov Chemistry Institute, Kazan Federal University, 420008 Kazan, Russia
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