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Li L, Li M, Qiu Y, Wang S, Dong Y. Aptamers capable of simultaneously identifying multiple targets and corresponding applications in medical diagnosis-A review. Int J Biol Macromol 2025; 311:143666. [PMID: 40316072 DOI: 10.1016/j.ijbiomac.2025.143666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 04/20/2025] [Accepted: 04/28/2025] [Indexed: 05/04/2025]
Abstract
Aptamers, a unique class of nucleic acid sequences recognized for their specific binding capabilities, have found widespread application in biomedical field. While traditional aptamers are typically designed to target a single molecule recognition, recent attention has been directed towards multifunctional aptamers capable of simultaneously identifying multiple targets. In this review, the latest advancements in multifunctional aptamers and their applications in medical diagnosis are presented for the first time. This review focuses on the following essential aspects, including methods employed for developing multifunctional aptamers, detailed characteristics of these aptamers, practical applications across diverse diagnostic scenarios, and in-depth discussions on critical aspects of their design and utility. To conclude, future perspectives are provided to drive further development and broader application of multifunctional aptamers in the biomedical domain.
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Affiliation(s)
- Ling Li
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, PR China
| | - Menglei Li
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, PR China
| | - Yinghua Qiu
- Center for Molecular Diagnostics and Precision Medicine, Institute for Molecular Medicine and Infectious Disease, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia 19102, USA
| | - Sai Wang
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, PR China
| | - Yiyang Dong
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, PR China.
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Huang Y, Lin G, Liu S, Chen M, Yang C, Song Y. Aptamer-based Immune Checkpoint Inhibition for Cancer Immunotherapy. Chembiochem 2025; 26:e202400599. [PMID: 39417693 DOI: 10.1002/cbic.202400599] [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: 07/16/2024] [Revised: 10/12/2024] [Accepted: 10/15/2024] [Indexed: 10/19/2024]
Abstract
Cancer has long been a significant threat to human life and health. The advent of immune checkpoint blockade strategies has reversed cancer-induced immune suppression, advanced the development of immunotherapy, and offered new hope in the fight against cancer. Aptamers, which possess the same specificity and affinity as antibodies, are advantageous due to their synthetic accessibility and ease of modification, providing novel insights for immune checkpoint research. In this review, we outline the key aptamers currently developed for immune checkpoints such as CTLA-4, PD-1, PD-L1 and Siglec-15. We explore their potential in therapeutic strategies, including functionalizing or engineering aptamers for covalent binding, valency control, and nanostructure assembly, as well as investigating molecular mechanisms such as glycosylated protein functions and cell-cell interactions. Finally, the future applications of aptamers in immunotherapy are discussed.
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Affiliation(s)
- Yihao Huang
- The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Xiamen University, Xiamen, Fujian, 361005, China
| | - Guihong Lin
- The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Xiamen University, Xiamen, Fujian, 361005, China
| | - Sinong Liu
- The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Xiamen University, Xiamen, Fujian, 361005, China
| | - Mingying Chen
- The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Xiamen University, Xiamen, Fujian, 361005, China
| | - Chaoyong Yang
- The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Xiamen University, Xiamen, Fujian, 361005, China
- Renji Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Yanling Song
- The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Xiamen University, Xiamen, Fujian, 361005, China
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Uinarni H, Oghenemaro EF, Menon SV, Hjazi A, Ibrahim FM, Kaur M, Zafarjonovna AZ, Deorari M, Jabir MS, Zwamel AH. Breaking Barriers: Nucleic Acid Aptamers in Gastrointestinal (GI) Cancers Therapy. Cell Biochem Biophys 2024; 82:1763-1776. [PMID: 38916791 DOI: 10.1007/s12013-024-01367-w] [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] [Accepted: 06/13/2024] [Indexed: 06/26/2024]
Abstract
Conventional cancer therapies can have significant adverse effects as they are not targeted to cancer cells and may damage healthy cells. Single-stranded oligonucleotides assembled in a particular architecture, known as aptamers, enable them to attach selectively to target areas. Usually, they are created by Systematic Evolution of Ligand by Exponential enrichment (SELEX), and they go through a rigorous pharmacological revision process to change their therapeutic half-life, affinity, and specificity. They could thus offer a viable substitute for antibodies in the targeted cancer treatment market. Although aptamers can be a better choice in some situations, antibodies are still appropriate for many other uses. The technique of delivering aptamers is simple and reasonable, and the time needed to manufacture them is relatively brief. Aptamers do not require animals or an immune response to be produced, in contrast to antibodies. When used as a medication, aptamers can directly suppress tumor cells. As an alternative, they can be included in systems for targeted drug delivery that administer medications specifically to tumor cells while reducing toxicity to healthy cells. The most recent and cutting-edge methods for treating gastrointestinal (GI) tract cancer with aptamers will be covered in this review, with a focus on targeted therapy as a means of conquering resistance to traditional medicines.
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Affiliation(s)
- Herlina Uinarni
- Department of Anatomy, School of Medicine and Health Sciences Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia.
- Radiology department of Pantai Indah Kapuk Hospital Jakarta, Jakarta, Indonesia.
| | - Enwa Felix Oghenemaro
- Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Delta State University, Abraka, Delta State, Nigeria
| | - Soumya V Menon
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
| | - Ahmed Hjazi
- Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia
| | - Fatma Magdi Ibrahim
- Assisstant professor, Community Health Nursing, RAK Medical and Health Sciences University, Ras Al Khaimah, UAE
- Lecturer, geriatric nursing, Mansoura University, Mansoura, Egypt
| | - Mandeep Kaur
- Department of Sciences, Vivekananda Global University, Jaipur, Rajasthan, 303012, India
| | | | - Mahamedha Deorari
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
| | - Majid S Jabir
- Department of applied sciences, University of technology, Baghdad, Iraq
| | - Ahmed Hussein Zwamel
- Medical laboratory technique college, the Islamic University, Najaf, Iraq
- Medical laboratory technique college, the Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq
- Medical laboratory technique college, the Islamic University of Babylon, Babylon, Iraq
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4
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Yan B, Li Y, He S. Aptamer-mediated therapeutic strategies provide a potential approach for cancer. Int Immunopharmacol 2024; 136:112356. [PMID: 38820957 DOI: 10.1016/j.intimp.2024.112356] [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: 04/04/2024] [Revised: 05/21/2024] [Accepted: 05/24/2024] [Indexed: 06/02/2024]
Abstract
The treatment of tumors still faces considerable challenges. While conventional treatments such as surgery, chemotherapy, and radiation therapy provide some curative effects, their side effects and limitations highlight the importance of finding more precise treatment strategies. Aptamers have become an important target molecule in the field of drug delivery systems due to their good affinity and targeting, and they have gradually become an important link from basic research to clinical application. In this paper, we discussed the latest progress of aptamer-mediated nanodrugs, as well as aptamer-mediated photodynamic therapy, photothermal therapy, and immunotherapy strategies for tumor treatment, and explored the possibility of aptamer-mediated therapy for accurate tumor treatment. The purpose of this review is to provide novel insights for treating tumors with aptamer-mediated therapies by summarizing these innovative strategies, thereby ultimately enhancing the therapeutic efficacy for cancer patients.
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Affiliation(s)
- Bingshuo Yan
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China
| | - Yuting Li
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China
| | - Shiming He
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China.
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5
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Lin X, Kang K, Chen P, Zeng Z, Li G, Xiong W, Yi M, Xiang B. Regulatory mechanisms of PD-1/PD-L1 in cancers. Mol Cancer 2024; 23:108. [PMID: 38762484 PMCID: PMC11102195 DOI: 10.1186/s12943-024-02023-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: 11/10/2023] [Accepted: 05/10/2024] [Indexed: 05/20/2024] Open
Abstract
Immune evasion contributes to cancer growth and progression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. The programmed death protein 1 (PD-1) and programmed cell death ligands (PD-Ls) are considered to be the major immune checkpoint molecules. The interaction of PD-1 and PD-L1 negatively regulates adaptive immune response mainly by inhibiting the activity of effector T cells while enhancing the function of immunosuppressive regulatory T cells (Tregs), largely contributing to the maintenance of immune homeostasis that prevents dysregulated immunity and harmful immune responses. However, cancer cells exploit the PD-1/PD-L1 axis to cause immune escape in cancer development and progression. Blockade of PD-1/PD-L1 by neutralizing antibodies restores T cells activity and enhances anti-tumor immunity, achieving remarkable success in cancer therapy. Therefore, the regulatory mechanisms of PD-1/PD-L1 in cancers have attracted an increasing attention. This article aims to provide a comprehensive review of the roles of the PD-1/PD-L1 signaling in human autoimmune diseases and cancers. We summarize all aspects of regulatory mechanisms underlying the expression and activity of PD-1 and PD-L1 in cancers, including genetic, epigenetic, post-transcriptional and post-translational regulatory mechanisms. In addition, we further summarize the progress in clinical research on the antitumor effects of targeting PD-1/PD-L1 antibodies alone and in combination with other therapeutic approaches, providing new strategies for finding new tumor markers and developing combined therapeutic approaches.
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Affiliation(s)
- Xin Lin
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
- Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, 410008, Hunan, China
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, 410078, Hunan, China
| | - Kuan Kang
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
- Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, 410008, Hunan, China
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, 410078, Hunan, China
| | - Pan Chen
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China
| | - Zhaoyang Zeng
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
- Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, 410008, Hunan, China
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, 410078, Hunan, China
| | - Guiyuan Li
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
- Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, 410008, Hunan, China
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, 410078, Hunan, China
| | - Wei Xiong
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China
- FuRong Laboratory, Changsha, 410078, Hunan, China
- Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, 410008, Hunan, China
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, 410078, Hunan, China
| | - Mei Yi
- Department of Dermotology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
| | - Bo Xiang
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China.
- FuRong Laboratory, Changsha, 410078, Hunan, China.
- Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, 410008, Hunan, China.
- The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, 410078, Hunan, China.
- Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Tongzipo Road, Changsha, 410013, Hunan, China.
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6
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Yin X, Rong J, Shao M, Zhang S, Yin L, He Z, Wang X. Aptamer-functionalized nanomaterials (AFNs) for therapeutic management of hepatocellular carcinoma. J Nanobiotechnology 2024; 22:243. [PMID: 38735927 PMCID: PMC11089756 DOI: 10.1186/s12951-024-02486-5] [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: 01/06/2024] [Accepted: 04/17/2024] [Indexed: 05/14/2024] Open
Abstract
Hepatocellular carcinoma (HCC) represents one of the deadliest cancers globally, making the search for more effective diagnostic and therapeutic approaches particularly crucial. Aptamer-functionalized nanomaterials (AFNs), an innovative nanotechnology, have paved new pathways for the targeted diagnosis and treatment of HCC. Initially, we outline the epidemiological background of HCC and the current therapeutic challenges. Subsequently, we explore in detail how AFNs enhance diagnostic and therapeutic efficiency and reduce side effects through the specific targeting of HCC cells and the optimization of drug delivery. Furthermore, we address the challenges faced by AFNs in clinical applications and future research directions, with a particular focus on enhancing their biocompatibility and assessing long-term effects. In summary, AFNs represent an avant-garde therapeutic approach, opening new avenues and possibilities for the diagnosis and treatment of HCC.
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Affiliation(s)
- Xiujuan Yin
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China
| | - Jing Rong
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China
| | - Min Shao
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China
| | - Saisai Zhang
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China
| | - Likang Yin
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China
| | - Zhenqiang He
- Clinical Medical College, Hebei University, Baoding, 071002, Hebei, China
| | - Xiao Wang
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.
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7
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Ayass MA, Tripathi T, Griko N, Okyay T, Ramankutty Nair R, Zhang J, Zhu K, Melendez K, Pashkov V, Abi-Mosleh L. Dual Checkpoint Aptamer Immunotherapy: Unveiling Tailored Cancer Treatment Targeting CTLA-4 and NKG2A. Cancers (Basel) 2024; 16:1041. [PMID: 38473398 DOI: 10.3390/cancers16051041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 02/13/2024] [Accepted: 02/28/2024] [Indexed: 03/14/2024] Open
Abstract
Recent strides in immunotherapy have illuminated the crucial role of CTLA-4 and PD-1/PD-L1 pathways in contemporary oncology, presenting both promises and challenges in response rates and adverse effects. This study employs a computational biology tool (in silico approach) to craft aptamers capable of binding to dual receptors, namely, inhibitory CTLA4 and NKG2A, thereby unleashing both T and NK cells and enhancing CD8+ T and NK cell functions for tumor cell lysis. Computational analysis highlighted AYA22T-R2-13 with HADDOCK scores of -78.2 ± 10.2 (with CTLA4), -60.0 ± 4.2 (with NKG2A), and -77.5 ± 5.6 (with CD94/NKG2A). Confirmation of aptamer binding to targeted proteins was attained via ELISA and flow cytometry methods. In vitro biological functionality was assessed using lactate dehydrogenase (LDH) cytotoxicity assay. Direct and competitive assays using ELISA and flow cytometry demonstrated the selective binding of AYA22T-R2-13 to CTLA4 and NKG2A proteins, as well as to the cell surface receptors of IL-2-stimulated T cells and NK cells. This binding was inhibited in the presence of competition from CTLA4 or NKG2A proteins. Remarkably, the blockade of CTLA4 or NKG2A by AYA22T-R2-13 augmented human CD8 T cell- and NK cell-mediated tumor cell lysis in vitro. Our findings highlight the precise binding specificity of AYA22T-R2-13 for CTLA4-B7-1/B7-2 (CD80/CD86) or CD94/NKG2A-HLA-E interactions, positioning it as a valuable tool for immune checkpoint blockade aptamer research in murine tumor models. These in vitro studies establish a promising foundation for further enhancing binding capacity and establishing efficacy and safety in animal models. Consequently, our results underscore the potential of AYA22T-R2-13 in cancer immunotherapy, offering high specificity, low toxicity, and the potential for cost-effective production.
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Affiliation(s)
| | | | - Natalya Griko
- Ayass Bioscience LLC, 8501 Wade Blvd, Bld 9, Frisco, TX 75034, USA
| | - Tutku Okyay
- Ayass Bioscience LLC, 8501 Wade Blvd, Bld 9, Frisco, TX 75034, USA
| | | | - Jin Zhang
- Ayass Bioscience LLC, 8501 Wade Blvd, Bld 9, Frisco, TX 75034, USA
| | - Kevin Zhu
- Ayass Bioscience LLC, 8501 Wade Blvd, Bld 9, Frisco, TX 75034, USA
| | - Kristen Melendez
- Ayass Bioscience LLC, 8501 Wade Blvd, Bld 9, Frisco, TX 75034, USA
| | - Victor Pashkov
- Ayass Bioscience LLC, 8501 Wade Blvd, Bld 9, Frisco, TX 75034, USA
| | - Lina Abi-Mosleh
- Ayass Bioscience LLC, 8501 Wade Blvd, Bld 9, Frisco, TX 75034, USA
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8
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Li Y, Liu W, Xu H, Zhou Y, Xie W, Guo Y, Liao Z, Jiang X, Liu J, Ren C. Aptamers combined with immune checkpoints for cancer detection and targeted therapy: A review. Int J Biol Macromol 2024; 262:130032. [PMID: 38342267 DOI: 10.1016/j.ijbiomac.2024.130032] [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: 08/03/2023] [Revised: 02/02/2024] [Accepted: 02/05/2024] [Indexed: 02/13/2024]
Abstract
In recent years, remarkable strides have been made in the field of immunotherapy, which has emerged as a standard treatment for many cancers. As a kind of immunotherapy drug, monoclonal antibodies employed in immune checkpoint therapy have proven beneficial for patients with diverse cancer types. However, owing to the extensive heterogeneity of clinical responses and the complexity and variability of the immune system and tumor microenvironment (TME), accurately predicting its efficacy remains a challenge. Recent advances in aptamers provide a promising approach for monitoring alterations within the immune system and TME, thereby facilitating targeted immunotherapy, particularly focused on immune checkpoint blockade, with enhanced antitumor efficiency. Aptamers have been widely used in tumor cell detection, biosensors, drug discovery, and biomarker screening due to their high specificity and high affinity with their targets. This review aims to comprehensively examine the research status and progress of aptamers in cancer diagnosis and immunotherapy, with a specific emphasis on those related to immune checkpoints. Additionally, we will discuss the future research directions and potential therapeutic targets for aptamer-based immune checkpoint therapy, aiming to provide a theoretical basis for targeting immunotherapy molecules and blocking tumor immune escape.
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Affiliation(s)
- Yihan Li
- NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China
| | - Weidong Liu
- NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China
| | - Hongjuan Xu
- NHC Key Laboratory of Biological Nanotechnology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Yao Zhou
- NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China
| | - Wen Xie
- NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China
| | - Youwei Guo
- NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China
| | - Ziling Liao
- NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China
| | - Xingjun Jiang
- NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Jie Liu
- Department of Critical care medicine, Hainan Hospital of Chinese PLA General Hosptial; project supported by Hainan Province Clinical Medical Center, China.
| | - Caiping Ren
- NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China.
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9
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Wu H, Lin J, Ling N, Zhang Y, He Y, Qiu L, Tan W. Functional Nucleic Acid-Based Immunomodulation for T Cell-Mediated Cancer Therapy. ACS NANO 2024; 18:119-135. [PMID: 38117770 DOI: 10.1021/acsnano.3c09861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2023]
Abstract
T cell-mediated immunity plays a pivotal role in cancer immunotherapy. The anticancer actions of T cells are coordinated by a sequence of biological processes, including the capture and presentation of antigens by antigen-presenting cells (APCs), the activation of T cells by APCs, and the subsequent killing of cancer cells by activated T cells. However, cancer cells have various means to evade immune responses. Meanwhile, these vulnerabilities provide potential targets for cancer treatments. Functional nucleic acids (FNAs) make up a class of synthetic nucleic acids with specific biological functions. With their diverse functionality, good biocompatibility, and high programmability, FNAs have attracted widespread interest in cancer immunotherapy. This Review focuses on recent research progress in employing FNAs as molecular tools for T cell-mediated cancer immunotherapy, including corresponding challenges and prospects.
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Affiliation(s)
- Hui Wu
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), The Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China
| | - Jie Lin
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China
| | - Neng Ling
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China
| | - Yutong Zhang
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China
| | - Yao He
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China
| | - Liping Qiu
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), The Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China
| | - Weihong Tan
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), The Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China
- Institute of Molecular Medicine (IMM), Renji Hospital, Shanghai Jiao Tong University School of Medicine, College of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
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10
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Bertrand P. Aptamers Targeting the PD-1/PD-L1 Axis: A Perspective. J Med Chem 2023; 66:10878-10888. [PMID: 37561598 DOI: 10.1021/acs.jmedchem.3c00551] [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: 08/12/2023]
Abstract
Aptamers have emerged in recent years as alternatives to antibodies or small molecules to interfere with the immune check points by blocking the PD-1/PD-L1 interactions and represent an interesting perspective for immuno-oncology. Aptamers are RNA or DNA nucleotides able to bind to a target with high affinity, with the target ranging from small molecules to proteins and up to cells. Aptamers are identified by the SELEX method that can be modified for specific purposes. The range of applications of aptamers covers therapy as well as new alternative assay technologies similar to ELISA. Aptamers' limited plasma stability can be managed using delivery strategies. The goal of this Perspective is to give an overview of the current development of aptamers targeting the most studied immune checkpoint modulators, PD-1 and PD-L1, and analogous strategies with aptamers for other immuno-related targets.
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Affiliation(s)
- Philippe Bertrand
- University of Poitiers, IC2MP UMR 7285 CNRS, 4 rue Michel Brunet B27, TSA 51106, 86073 Poitiers cedex 9, France
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11
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Ding F, Zhang S, Chen Q, Feng H, Ge Z, Zuo X, Fan C, Li Q, Xia Q. Immunomodulation with Nucleic Acid Nanodevices. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2023; 19:e2206228. [PMID: 36599642 DOI: 10.1002/smll.202206228] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 12/09/2022] [Indexed: 06/17/2023]
Abstract
The precise regulation of interactions of specific immunological components is crucial for controllable immunomodulation, yet it remains a great challenge. With the assistance of advanced computer design, programmable nucleic acid nanotechnology enables the customization of synthetic nucleic acid nanodevices with unprecedented geometrical and functional precision, which have shown promising potential for precise immunoengineering. Notably, the inherently immunologic functions of nucleic acids endow these nucleic acid-based assemblies with innate advantages in immunomodulatory engagement. In this review, the roles of nucleic acids in innate immunity are discussed, focusing on the definition, immunologic modularity, and enhanced bioavailability of structural nucleic acid nanodevices. In light of this, molecular programming and precise organization of functional modules with nucleic acid nanodevices for immunomodulation are emphatically reviewed. At last, the present challenges and future perspectives of nucleic acid nanodevices for immunomodulation are discussed.
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Affiliation(s)
- Fei Ding
- Shanghai Institute of Transplantation, Department of Liver Surgery, Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P. R. China
| | - Shuangye Zhang
- School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China
| | - Qian Chen
- Shanghai Institute of Transplantation, Department of Liver Surgery, Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P. R. China
| | - Hao Feng
- Shanghai Institute of Transplantation, Department of Liver Surgery, Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P. R. China
| | - Zhilei Ge
- School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China
| | - Xiaolei Zuo
- Shanghai Institute of Transplantation, Department of Liver Surgery, Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P. R. China
- School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China
| | - Chunhai Fan
- School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China
| | - Qian Li
- School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China
- WLA Laboratories, World Laureates Association, Shanghai, 201203, P. R. China
| | - Qiang Xia
- Shanghai Institute of Transplantation, Department of Liver Surgery, Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P. R. China
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12
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Agnello L, d’Argenio A, Nilo R, Fedele M, Camorani S, Cerchia L. Aptamer-Based Strategies to Boost Immunotherapy in TNBC. Cancers (Basel) 2023; 15:cancers15072010. [PMID: 37046670 PMCID: PMC10093095 DOI: 10.3390/cancers15072010] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 03/24/2023] [Accepted: 03/26/2023] [Indexed: 03/30/2023] Open
Abstract
The immune system (IS) may play a crucial role in preventing tumor development and progression, leading, over the last years, to the development of effective cancer immunotherapies. Nevertheless, immune evasion, the capability of tumors to circumvent destructive host immunity, remains one of the main obstacles to overcome for maximizing treatment success. In this context, promising strategies aimed at reshaping the tumor immune microenvironment and promoting antitumor immunity are rapidly emerging. Triple-negative breast cancer (TNBC), an aggressive breast cancer subtype with poor outcomes, is highly immunogenic, suggesting immunotherapy is a viable strategy. As evidence of this, already, two immunotherapies have recently become the standard of care for patients with PD-L1 expressing tumors, which, however, represent a low percentage of patients, making more active immunotherapeutic approaches necessary. Aptamers are short, highly structured, single-stranded oligonucleotides that bind to their protein targets at high affinity and specificity. They are used for therapeutic purposes in the same way as monoclonal antibodies; thus, various aptamer-based strategies are being actively explored to stimulate the IS’s response against cancer cells. The aim of this review is to discuss the potential of the recently reported aptamer-based approaches to boost the IS to fight TNBC.
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13
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Zhong G, Lin Y, Huang Z. Identification of a novel circRNA-miRNA-mRNA regulatory axis in hepatocellular carcinoma based on bioinformatics analysis. Sci Rep 2023; 13:3728. [PMID: 36878930 PMCID: PMC9988886 DOI: 10.1038/s41598-023-30567-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Accepted: 02/25/2023] [Indexed: 03/08/2023] Open
Abstract
In recent years, circular RNAs (circRNAs) have been found to play an essential regulatory role in hepatocellular carcinoma (HCC) through various mechanisms, particularly the endogenous competitive RNA (ceRNA) mechanism. Therefore, it is significant to explore the circRNAs in hepatoma. In this study, we constructed the ceRNA and survival network using Cytoscape. We also used R, Perl software, and multiple online databases and platforms, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), to perform overall survival, immune cell infiltration, immune checkpoints, pathway activity, and anticancer drug sensitivity analysis of the genes. Finally, the receiver operator characteristic curve (ROC) analysis was performed to identify the diagnosis value of the genes. KEGG analysis revealed the T cell receptor signaling pathway as the main enrichment pathway. A total of 29 genes related to survival and prognosis were screened out. The findings suggest that ZNF544, WDR76, ACTG1, RASSF3, E2F3, ASRGL1, and POGK are associated with multilevel immune cell infiltration. Additionally, immune checkpoint analysis screened out the ACTG1, E2F3, RASSF3, and WDR76. It was also revealed that the WDR76, E2F3, ASRGL1, and POGK mainly activated the cell cycle and DNA damage response (DDR) pathway. The results suggest that the sensitivity toward trametinib, refametinib (RDEA119), and selumetinib correlates to the expression of WDR76. ROC analysis showed that the area under the curve (AUC) of all genes in the regulatory axis was greater than 0.7. The identified hsa_circ_0000417/hsa_circ_0002688/hsa_circ_0001387--hsa-miR-199a-5p--WDR76 regulatory axis may provide new insights into the progression, clinical diagnosis, and treatment of HCC.
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Affiliation(s)
- Guoqiang Zhong
- Department of Gastroenterology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China.,The Graduate School, Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China
| | - Yan Lin
- Department of Gastroenterology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China.,The Graduate School, Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China
| | - Zansong Huang
- Department of Gastroenterology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China. .,The Graduate School, Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China.
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14
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Wang Y, Wu M, Wang X, Wang P, Ning Z, Zeng Y, Liu X, Sun H, Zheng A. Biodegradable MnO 2-based gene-engineered nanocomposites for chemodynamic therapy and enhanced antitumor immunity. Mater Today Bio 2023; 18:100531. [PMID: 36619204 PMCID: PMC9812708 DOI: 10.1016/j.mtbio.2022.100531] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 12/20/2022] [Accepted: 12/26/2022] [Indexed: 12/29/2022] Open
Abstract
Immune checkpoint blockade (ICB) is emerging as a promising therapeutic approach for clinical treatment against various cancers. However, ICB based monotherapies still suffer from low immune response rate due to the limited and exhausted tumor-infiltrating lymphocytes as well as tumor immunosuppressive microenvironment. In this work, the cell membrane with surface displaying PD-1 proteins (PD1-CM) was prepared for immune checkpoint blockade, which was further combined with multifunctional and biodegradable MnO2 for systematic and robust antitumor therapy. The MnO2-based gene-engineered nanocomposites can catalyze the decomposition of abundant H2O2 in TME to generate O2, which can promote the intratumoral infiltration of T cells, and thus improve the effect of immune checkpoint blockade by PD-1 proteins on PD1-CM. Furthermore, MnO2 in the nanocomposites can be completely degraded into Mn2+, which can catalyze the generation of highly toxic hydroxyl radicals for chemodynamic therapy, thereby further enhancing the therapeutic effect. In addition, the prepared nanocomposites possess the advantages of low cost, easy preparation and good biocompatibility, which are expected to become promising agents for combination immunotherapy.
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Affiliation(s)
- Yiru Wang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR China
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, 350116, PR China
| | - Ming Wu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR China
| | - Xiaorong Wang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR China
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, 350116, PR China
| | - Peiyuan Wang
- Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, PR China
| | - Zhaoyu Ning
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR China
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, 350116, PR China
| | - Yongyi Zeng
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR China
| | - Xiaolong Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR China
- Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, PR China
| | - Haiyan Sun
- Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, PR China
| | - Aixian Zheng
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR China
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15
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García Melián MF, Moreno M, Cerecetto H, Calzada V. Aptamer-Based Immunotheranostic Strategies. Cancer Biother Radiopharm 2023; 38:246-255. [PMID: 36603108 DOI: 10.1089/cbr.2022.0064] [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: 01/07/2023] Open
Abstract
The escape from immune surveillance is a hallmark of cancer progression. The classic immune checkpoint molecules PD-1, PD-L1, CTLA-4, LAG-3, TIM-3 novel ones are part of a sophisticated system of up- and downmodulation of the immune system, which is unregulated in cancer. In recent years, there have been remarkable advances in the development of targeting strategies, focused principally on immunotherapies aiming at blocking those molecules involved in the evasion of the immune system. However, there are still challenges to predicting their efficacy due to the wide heterogeneity of clinical responses. Thus, there is a need to develop new strategies, and theranostics has much to contribute in this field. Besides that, aptamers have emerged as promising molecules with the potential to generate a huge impact in the immunotheranostic field. They are single-stranded oligonucleotides with a unique self-folding tridimensional structure, with high affinity and specificity for the target. In particular, their small size and physicochemical characteristics make them a versatile tool for designing theranostic strategies. Here, we review the progress in theranostic strategies based on aptamers against immune checkpoints, and highlight the potential of those approaches.
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Affiliation(s)
- María Fernanda García Melián
- Área de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
| | - María Moreno
- Departamento de Desarrollo Biotecnológico, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
| | - Hugo Cerecetto
- Área de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
| | - Victoria Calzada
- Área de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
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16
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Wu L, Zhang Y, Wang Z, Zhang Y, Zou J, Qiu L. Aptamer-Based Cancer Cell Analysis and Treatment. ChemistryOpen 2022; 11:e202200141. [PMID: 36264016 PMCID: PMC9583543 DOI: 10.1002/open.202200141] [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: 06/18/2022] [Revised: 08/31/2022] [Indexed: 11/09/2022] Open
Abstract
Aptamers are a class of single-stranded DNA or RNA oligonucleotides that can exclusively bind to various targets with high affinity and selectivity. Regarded as "chemical antibodies", aptamers possess several intrinsic advantages, including easy synthesis, convenient modification, high programmability, and good biocompatibility. In recent decades, many studies have demonstrated the superiority of aptamers as molecular tools for various biological applications, particularly in the area of cancer theranostics. In this review, we focus on recent progress in developing aptamer-based strategies for the precise analysis and treatment of cancer cells.
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Affiliation(s)
- Limei Wu
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering College of Biology, Aptamer Engineering Center of Hunan ProvinceHunan UniversityChangsha, Hunan410082P. R. China
| | - Yutong Zhang
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering College of Biology, Aptamer Engineering Center of Hunan ProvinceHunan UniversityChangsha, Hunan410082P. R. China
| | - Zhimin Wang
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering College of Biology, Aptamer Engineering Center of Hunan ProvinceHunan UniversityChangsha, Hunan410082P. R. China
| | - Yue Zhang
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering College of Biology, Aptamer Engineering Center of Hunan ProvinceHunan UniversityChangsha, Hunan410082P. R. China
| | - Jianmei Zou
- Guangxi Key Laboratory of Electrochemical and Magnetochemical Function Materials, College of Chemistry and BioengineeringGuilin University of TechnologyGuilin, Guangxi541004P. R. China
| | - Liping Qiu
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering College of Biology, Aptamer Engineering Center of Hunan ProvinceHunan UniversityChangsha, Hunan410082P. R. China
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17
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Intercellular communication in the tumour microecosystem: Mediators and therapeutic approaches for hepatocellular carcinoma. Biochim Biophys Acta Mol Basis Dis 2022; 1868:166528. [PMID: 36007784 DOI: 10.1016/j.bbadis.2022.166528] [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] [Received: 06/01/2022] [Revised: 08/10/2022] [Accepted: 08/18/2022] [Indexed: 11/24/2022]
Abstract
Hepatocellular carcinoma (HCC), one of the most common tumours worldwide, is one of the main causes of mortality in cancer patients. There are still numerous problems hindering its early diagnosis, which lead to late patients receiving treatment, and these problems need to be solved urgently. The tumour microecosystem is a complex network system comprising seven parts: the hypoxia niche, immune microenvironment, metabolic microenvironment, acidic niche, innervated niche, mechanical microenvironment, and microbial microenvironment. Intercellular communication is divided into direct contact and indirect communication. Direct contact communication includes gap junctions, tunneling nanotubes, and receptor-ligand interactions, whereas indirect communication includes exosomes, apoptotic vesicles, and soluble factors. Mechanical communication and cytoplasmic exchange are further means of intercellular communication. Intercellular communication mediates the crosstalk between the tumour microecosystem and the host as well as that between cells and cell-free components in the tumour microecosystem, causing changes in the tumour hallmarks of the HCC microecosystem such as changes in tumour proliferation, invasion, apoptosis, angiogenesis, metastasis, inflammatory response, gene mutation, immune escape, metabolic reprogramming, and therapeutic resistance. Here, we review the role of the above-mentioned intercellular communication in the HCC microecosystem and discuss the advantages of targeted intercellular communication in the clinical diagnosis and treatment of HCC. Finally, the current problems and prospects are discussed.
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18
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Li J, Tian X, Nie Y, He Y, Wu W, Lei X, Zhang T, Wang Y, Mao Z, Zhang H, Zhang X, Song W. BTBD10 is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma. Front Mol Biosci 2022; 8:762541. [PMID: 35059434 PMCID: PMC8764259 DOI: 10.3389/fmolb.2021.762541] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Accepted: 12/03/2021] [Indexed: 12/24/2022] Open
Abstract
Background: BTBD10 serves as an activator of Akt family members through decreasing the protein phosphatase 2A-mediated dephosphorylation. The present study attempted to investigate the prognostic value of BTBD10 in hepatocellular carcinoma (HCC), specially, its relationship with tumor-infiltrating lymphocytes (TILs). Methods: BTBD10 expression was evaluated in HCC using The Cancer Genome Atlas (TCGA) and Xijing Hospital database, and verified in HCC cell lines. Cox analyses were performed to analyze independent prognostic risk factors for HCC. The optimal cut-off value of BTBD10 was calculated, by which all patients were divided into two groups to compare the overall survival (OS). The signaling pathways were predicted, by which BTBD10 may affect the progression of HCC. To investigate the impact of BTBD10 on HCC immunotherapy, correlations between BTBD10 and TILs, immune checkpoints, m6A methylation-related genes and ferroptosis-related genes were assessed. The distribution of half-maximal inhibitory concentration (IC50) of diverse targeted drugs was observed based on the differential expression of BTBD10. Results: BTBD10 expression was higher in HCC tissues and cell lines than that of normal liver tissues and cells. The patients with high expression of BTBD10 showed a worse OS, as compared to that of BTBD10 low-expressing group. Cox analyses indicated that BTBD10 was an independent prognostic risk factor for HCC. Several molecular pathways of immune responses were activated in HCC patients with high-expressing of BTBD10. Furthermore, BTBD10 expression was demonstrated to be positively correlated with tumor-infiltrating B cells, T cells, macrophages, neutrophils and dendritic cells. Meanwhile, the expression of BTBD10 was synchronized with that of several m6A methylation-related genes, ferroptosis-related genes and immune checkpoints. The IC50 scores of Sorafenib, Navitoclax, Veliparib, Luminespib, and Imatinib were found to be lower in BTBD10 high-expressing HCC group. Conclusion: BTBD10 negatively regulates tumor immunity in HCC and exhibits adverse effect on the prognosis of HCC, which could be a potential target for immunotherapy.
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Affiliation(s)
- Jianhui Li
- Xi'an Medical University, Xi'an, China.,Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Xiaojuan Tian
- Operating Room, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Ye Nie
- Xi'an Medical University, Xi'an, China.,Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Ying He
- Xi'an Medical University, Xi'an, China
| | - Wenlong Wu
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | | | | | | | | | - Hong Zhang
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Xuan Zhang
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Wenjie Song
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
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19
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Maru B, Nadeau L, McKeague M. Enhancing CAR-T Cell Therapy with Functional Nucleic Acids. ACS Pharmacol Transl Sci 2021; 4:1716-1727. [PMID: 34927006 DOI: 10.1021/acsptsci.1c00188] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Indexed: 02/07/2023]
Abstract
Chimeric antigen receptor (CAR) T cell therapy is a relatively new form of immunotherapy that has had success in treating patients with hematologic malignancies, leading to three recent United States Food and Drug Administration approvals. However, several challenges hinder the widespread use of CAR-T therapy. Here, we review the application of functional nucleic acids such as aptamers and ribozymes as novel tools to improve a variety of steps in CAR-T cell therapy development. We critically examine key studies that highlight the benefits of functional nucleic acids at different stages of cell-based therapy and discuss the feasibility of their practical clinical application. Finally, we offer insights into potential opportunities where chemists can significantly contribute to the innovative incorporation of functional nucleic acids to overcome challenges associated with this cutting-edge immunotherapy.
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Affiliation(s)
- Bruktawit Maru
- Pharmacology and Therapeutics, Faculty of Medicine, McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6, Canada
| | - Lea Nadeau
- Pharmacology and Therapeutics, Faculty of Medicine, McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6, Canada
| | - Maureen McKeague
- Pharmacology and Therapeutics, Faculty of Medicine, McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6, Canada.,Department of Chemistry, Faculty of Science, McGill University, 801 Sherbrooke Street West, Montreal, QC H3A 0B8, Canada
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20
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Nakhjavani M, Shigdar S. Future of PD-1/PD-L1 axis modulation for the treatment of triple-negative breast cancer. Pharmacol Res 2021; 175:106019. [PMID: 34861397 DOI: 10.1016/j.phrs.2021.106019] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 11/24/2021] [Accepted: 11/29/2021] [Indexed: 02/07/2023]
Abstract
Triple-negative breast cancer (TNBC) has the worst prognosis among the subtypes of breast cancer, with no targeted therapy available. Immunotherapy targeting programmed cell death protein-1 (PD-1) and its ligand (PD-L1) has resulted in some promising outcomes in cancer patients. The common treatments are monoclonal antibodies (mAbs). Despite novel methodologies in developing mAbs, there are several drawbacks with these medications. Immunological reactions, expensive and time-consuming production and requiring refrigeration are some of the challenging characteristics of mAbs that are addressed with using aptamers. Aptamers are nucleotide-based structures with high selectivity and specificity for target. Their small size helps aptamers penetrate the tissue better. In this review, we have discussed the nature of PD-1/PD-L1 interaction and summarised the available mAbs and aptamers specific for these two targets. This review highlights the role of aptamers as a future pathway for PD-1/PD-L1 modulation.
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Affiliation(s)
- Maryam Nakhjavani
- School of Medicine, Deakin University, Geelong, VIC 3220, Australia; Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, VIC 3220, Australia.
| | - Sarah Shigdar
- School of Medicine, Deakin University, Geelong, VIC 3220, Australia; Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, VIC 3220, Australia
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