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Zhang J, Zhang Q, Li X, Wei Y, Qiu M, Yang H, Sun X. Prominent supramolecular systems for cancer Therapy: From structural design to tailored applications. Eur J Med Chem 2025; 294:117754. [PMID: 40378574 DOI: 10.1016/j.ejmech.2025.117754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2025] [Revised: 04/29/2025] [Accepted: 05/09/2025] [Indexed: 05/19/2025]
Abstract
Supramolecular materials represent a powerful class of platforms in cancer diagnosis and therapy, owing to their dynamic architectures, stimuli responsiveness, and high biocompatibility. This review focused on three representative categories-Pillarene-based systems, virus-mimetic nanoparticles (VMNs), and metal-organic frameworks (MOFs)-each offering unique structural and functional properties. Pillarene-based assemblies enable precise host-guest interactions, by being classified into amphiphilic, ionic, and chiral varieties, the robust drug loading and controlled release capabilities of the Pillarene family were emphasized. At the same time, the VMNs, including virus-like particles and virosomes, show power in cancer cell targeting and membrane penetration by emulating natural viral architectures. By discussing the fabrication and application of single-metallic, multi-metallic, and composite MOFs, their potential in multimodal diagnosis and therapy was revealed. In addition, other supramolecular categories, such as cyclodextrin and dendrimers, were introduced as well. We highlighted representative approaches and emerging methods, and comparative perspectives with traditional nanocarriers were included. A critical evaluation of pharmacokinetic behaviors, biosafety concerns, and translational limitations was also proposed, aiming to guide future research in supramolecular cancer nanomedicine. Through an integrative and forward-looking analysis, this review provided a comprehensive framework for understanding and designing supramolecular systems for precision oncology. These emerging nanotechnologies hold promise to reshape cancer medicine by enabling adaptive, targeted, and multifunctional therapeutic strategies.
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Affiliation(s)
- Jiawei Zhang
- The First Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang, China; School of Intelligent Medicine, China Medical University, No.77, Puhe Road, Shenyang, China
| | - Qingya Zhang
- The First Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang, China; School of Forensic Medicine, China Medical University, No.77, Puhe Road, Shenyang, China
| | - Xiaojia Li
- Teaching Center for Basic Medical Experiment, China Medical University, No.77, Puhe Road, Shenyang, China
| | - Yixuan Wei
- Teaching Center for Basic Medical Experiment, China Medical University, No.77, Puhe Road, Shenyang, China
| | - Min Qiu
- Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Huazhe Yang
- School of Intelligent Medicine, China Medical University, No.77, Puhe Road, Shenyang, China.
| | - Xiaoting Sun
- School of Forensic Medicine, China Medical University, No.77, Puhe Road, Shenyang, China.
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Lin TC, Liu IJ, Chih HY, Tzang BS, Liang JA, Kuo CW, Hung CY, Hsu TC, Chiang WH. Photothermal-enhanced ROS storm by hyaluronic acid-conjugated nanocatalysts to amplify tumor-specific photo-chemodynamic therapy and immune response. Int J Biol Macromol 2025; 309:142975. [PMID: 40210075 DOI: 10.1016/j.ijbiomac.2025.142975] [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: 02/09/2025] [Revised: 03/28/2025] [Accepted: 04/07/2025] [Indexed: 04/12/2025]
Abstract
Integrating photodynamic therapy (PDT) and chemodynamic therapy (CDT) shows promising potential in tumor treatment. Nevertheless, the lack of specific tumor targeting, serious photobleaching, and poor photothermal effect of photosensitizers, the intracellular low Fenton reaction efficiency, and glutathione (GSH)-elicited reactive oxygen species (ROS) depletion profoundly restrict ROS-mediated cancer therapy. To enhance ROS generation with the assistance of photothermal therapy (PTT), the hyaluronic acid (HA)-decorated Fe-MIL-88B (MIL) nanocatalysts were fabricated for tumor-targeted delivery of photosensitizer IR820. The IR820@HA-coated MIL (IHM) nanocatalysts remarkably enhanced the photothermal conversion efficacy and singlet oxygen (1O2) production of IR820 and lowered IR820 photobleaching. The IHM nanocatalysts promoted the conversion of H2O2 into toxic ·OH upon thermo/acidity-enhanced Fe3+-mediated Fenton reaction and consumed GSH via Fe3+-elicited GSH oxidation. After being internalized by 4 T1 cancer cells via CD44-mediated endocytosis, the IHM nanocatalysts under irradiation of near-infrared (NIR) laser prominently produced hyperthermia and strong ROS storm, thereby causing apoptosis and ferroptosis via mitochondria damage and lipid peroxidation, and inducing immunogenic cell death (ICD). Through HA-mediated tumor targeting, the IHM nanocatalysts effectively accumulated in 4 T1 tumor and inhibited tumor growth and lung metastasis by PTT-enhanced PDT/CDT combined with ferroptosis and ICD-amplified antitumor immune response, showing great promise in future tumor treatment.
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Affiliation(s)
- Tzu-Chen Lin
- Department of Chemical Engineering, National Chung Hsing University, Taichung 402, Taiwan
| | - I-Ju Liu
- Department of Chemical Engineering, National Chung Hsing University, Taichung 402, Taiwan
| | - Hsiang-Yun Chih
- Department of Chemical Engineering, National Chung Hsing University, Taichung 402, Taiwan
| | - Bor-Show Tzang
- Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; Immunology Research Center, Chung Shan Medical University, Taichung 402, Taiwan; Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan
| | - Ju-An Liang
- Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
| | - Chia-Wei Kuo
- Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
| | - Chun-Yu Hung
- Department of Orthopedic Surgery, Jen-Ai Hospital, Taichung 402, Taiwan
| | - Tsai-Ching Hsu
- Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; Immunology Research Center, Chung Shan Medical University, Taichung 402, Taiwan; Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
| | - Wen-Hsuan Chiang
- Department of Chemical Engineering, National Chung Hsing University, Taichung 402, Taiwan; i-Center for Advanced Science and Technology (iCAST), National Chung Hsing University, Taichung 402, Taiwan.
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Zhang H, Liu H, Xie Z, Du J, Jin C. Hyaluronic acid-functionalized supramolecular nanophotosensitizers for targeted photoimmunotherapy of triple-negative breast cancer. J Nanobiotechnology 2024; 22:777. [PMID: 39702323 DOI: 10.1186/s12951-024-03044-9] [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: 08/17/2024] [Accepted: 11/29/2024] [Indexed: 12/21/2024] Open
Abstract
Triple-negative breast cancer (TNBC) is recognized as a particularly aggressive subtype of breast cancer that is devoid of effective therapeutic targets. Immune checkpoint inhibitors (ICIs) have demonstrated promising results in TNBC treatment. Nonetheless, most patients either develop resistance to ICIs or fail to respond to them initially. Owing to its spatio-temporal precision and non-invasive nature, photoimmunotherapy offers a targeted therapeutic strategy for TNBC. Herein, we report hyaluronic acid (HA)-functionalized indocyanine green-based supramolecular nanoparticles (HGI NPs), with biodegradable characteristics, for high-performance photoacoustic imaging and targeted phototherapy for TNBC. Notably, HGI NPs can significantly gather in TNBC tissues because of the enhanced permeability and retention effect of the tumor, and the tumor-targeting properties of HA. The strong amplification of HGI nanoparticles triggers a significant immunogenic cell death (ICD) response when exposed to 808 nm light, thus shifting the immunosuppressive tumor microenvironment (iTME) into a tumor attack mode and 'hot' state. Antitumor experiments demonstrate the high efficiency of the supramolecular photosensitizers HGI NPs for TNBC elimination and good biosafety. This synergistic strategy reshapes the iTME and amplifies the antitumor immune response, providing a theoretical foundation for combining phototherapy and ICIs as potential treatments for TNBC.
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Affiliation(s)
- Haiyan Zhang
- Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Hongxin Liu
- State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China
| | - Zhigang Xie
- State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China.
| | - Jianshi Du
- Key Laboratory and Engineering Laboratory of Lymphatic Surgery Jilin Province, China-Japan Union Hospital of Jilin University, Changchun, China.
| | - Chunxiang Jin
- Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, China.
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Chen Y, Mao K, Han D, Ma R, Sun T, Zhang H, Han B. Nanomedicine based on chemotherapy-induced immunogenic death combined with immunotherapy to enhance antitumor immunity. Front Pharmacol 2024; 15:1511423. [PMID: 39697556 PMCID: PMC11652165 DOI: 10.3389/fphar.2024.1511423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 11/18/2024] [Indexed: 12/20/2024] Open
Abstract
Introduction Chemo-immunotherapy based on inducing tumor immunogenic cell death (ICD)with chemotherapy drugs has filled the gaps between traditional chemotherapy and immunotherapy. It is verified that paclitaxel (PTX) can induce breast tumor ICD. From this basis, a kind of nanoparticle that can efficiently deliver different drug components simultaneously is constructed. The purpose of this study is for the sake of exploring the scheme of chemotherapy-induced ICD combined with other immunotherapy to enhance tumor immunogenicity and inhibit the growth, metastasis, and recurrence of breast tumors, so as to provide a research basis for solving the tough problem of breast cancer treatment. Methods Nanomedicine loaded with PTX, small interference RNA that suppresses CD47 expression (CD47siRNA, siCD47), and immunomodulator R848 were prepared by the double emulsification method. The hydrodynamic diameter and zeta potential of NP/PTX/siCD47/R848 were characterized. Established the tumor-bearing mice model of mouse breast cancer cell line (4T1) in situ and observed the effect of intravenous injection of NP/PTX/siCD47/R848 on the growth of 4T1 tumor in situ. Flow cytometry was used to detect the effect of drugs on tumor immune cells. Results NP/PTX/siCD47/R848 nano-drug with tumor therapeutic potential were successfully prepared by double emulsification method, with particle size of 121.5 ± 4.5 nm and surface potential of 36.1 ± 2.5 mV. The calreticulin on the surface of cell membrane and extracellular ATP or HMGB1 of 4T1 cells increased through treatment with NPs. NP/PTX-treated tumor cells could cause activation of BMDCs and BMDMs. After intravenous injection, NP/PTX could quickly reach the tumor site and accumulate for 24 h. The weight and volume of tumor in situ in the breast cancer model mice injected with nanomedicine through the tail vein were significantly lower than those in the PBS group. The ratio of CD8+/CD4+ T cells in the tumor microenvironment and the percentage of dendritic cells in peripheral blood increased significantly in breast cancer model mice injected with nano-drugs through the tail vein. Discussion Briefly, the chemotherapeutic drug paclitaxel can induce breast cancer to induce ICD. The nanomedicine which can deliver PTX, CD47siRNA, and R848 at the same time was prepared by double emulsification. NP/PTX/siCD47/R848 nano-drug can be enriched in the tumor site. The experiment of 4T1 cell tumor-bearing mice shows that the nano-drug can enhance tumor immunogenicity and inhibit breast tumor growth, which provides a new scheme for breast cancer treatment. (Graphical abstract).
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Affiliation(s)
- Yichang Chen
- Department of Breast Surgery, General Surgery Center of The First Hospital, Jilin University, Changchun, China
| | - Kuirong Mao
- Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, The First Hospital, Institute of Immunology, Jilin University, Changchun, China
- National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, China
| | - Dongxiao Han
- Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, The First Hospital, Institute of Immunology, Jilin University, Changchun, China
- National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, China
| | - Ruolin Ma
- Department of Breast Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, China
| | - Tianmeng Sun
- Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, The First Hospital, Institute of Immunology, Jilin University, Changchun, China
- National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, China
- International Center of Future Science, Jilin University, Changchun, China
| | - Haipeng Zhang
- Department of Gynecology, Obstetrics and Gynecology Center, The First Hospital of Jilin University, Changchun, China
| | - Bing Han
- Department of Breast Surgery, General Surgery Center of The First Hospital, Jilin University, Changchun, China
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Yeh NT, Lin TC, Liu IJ, Hu SH, Hsu TC, Chin HY, Tzang BS, Chiang WH. Hyaluronic acid-covered ferric ion-rich nanobullets with high zoledronic acid payload for breast tumor-targeted chemo/chemodynamic therapy. Int J Biol Macromol 2024; 279:135271. [PMID: 39233170 DOI: 10.1016/j.ijbiomac.2024.135271] [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: 06/22/2024] [Revised: 08/23/2024] [Accepted: 08/31/2024] [Indexed: 09/06/2024]
Abstract
Due to the heterogeneity of the tumor microenvironment, the clinical efficacy of tumor treatment is not satisfied, highlighting the necessity for new strategies to tackle this issue. To effectively treat breast tumors by tumor-targeted chemo/chemodynamic therapy, herein, the Fe3+-rich MIL-88B nanobullets (MNs) covered with hyaluronic acid (HA) were fabricated as vehicles of zoledronic acid (ZA). The attained ZA@HMNs showed a high ZA payload (ca 29.6 %), outstanding colloidal stability in the serum-containing milieu, and accelerated ZA as well as Fe3+ release under weakly acidic and glutathione (GSH)-rich conditions. Also, the ZA@HMNs consumed GSH by GSH-mediated Fe3+ reduction and converted H2O2 into OH via Fenton or Fenton-like reaction with pH reduction. After being internalized by 4T1 cells upon CD44-mediated endocytosis, the ZA@HMNs depleted intracellular GSH and degraded H2O2 into OH, thus eliciting lipid peroxidation and mitochondria damage to suppress cell proliferation. Also, the ZA@HMNs remarkably killed macrophage-like RAW 264.7 cells. Importantly, the in vivo studies and ki67 and GPX4 staining of tumor sections demonstrated that the ZA@HMNs efficiently accumulated in 4T1 tumors to hinder tumor growth via ZA chemotherapy combined with OH-mediated ferroptosis. This work presents a practicable strategy to fabricate ZA@HMNs for breast tumor-targeted chemo/chemodynamic therapy with potential clinical translation.
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Affiliation(s)
- Nien-Tzu Yeh
- Department of Chemical Engineering, i-Center for Advanced Science and Technology (iCAST), National Chung Hsing University, Taichung 402, Taiwan
| | - Tzu-Chen Lin
- Department of Chemical Engineering, i-Center for Advanced Science and Technology (iCAST), National Chung Hsing University, Taichung 402, Taiwan
| | - I-Ju Liu
- Department of Chemical Engineering, i-Center for Advanced Science and Technology (iCAST), National Chung Hsing University, Taichung 402, Taiwan
| | - Shang-Hsiu Hu
- Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan
| | - Tsai-Ching Hsu
- Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; Immunology Research Center, Chung Shan Medical University, Taichung 402, Taiwan; Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan
| | - Hao-Yang Chin
- Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
| | - Bor-Show Tzang
- Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; Immunology Research Center, Chung Shan Medical University, Taichung 402, Taiwan; Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan; Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
| | - Wen-Hsuan Chiang
- Department of Chemical Engineering, i-Center for Advanced Science and Technology (iCAST), National Chung Hsing University, Taichung 402, Taiwan.
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Khafaga DSR, El-Morsy MT, Faried H, Diab AH, Shehab S, Saleh AM, Ali GAM. Metal-organic frameworks in drug delivery: engineering versatile platforms for therapeutic applications. RSC Adv 2024; 14:30201-30229. [PMID: 39315019 PMCID: PMC11418013 DOI: 10.1039/d4ra04441j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 08/30/2024] [Indexed: 09/25/2024] Open
Abstract
Recently, metal-organic frameworks (MOFs) have attracted much attention as versatile materials for drug delivery and personalized medicine. MOFs are porous structures made up of metal ions coupled with organic ligands. This review highlights the synthesis techniques used to design MOFs with specific features such as surface area and pore size, and the drug encapsulation within MOFs not only improves their stability and solubility but also allows for controlled release kinetics, which improves therapeutic efficacy and minimizes adverse effects. Furthermore, it discusses the challenges and potential advantages of MOF-based drug delivery, such as MOF stability, biocompatibility, and scale-up production. With further advancements in MOF synthesis, functionalization techniques, and understanding of their interactions using biological systems, MOFs can have significant promise for expanding the area of personalized medicine and improving patient outcomes.
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Affiliation(s)
- Doaa S R Khafaga
- Health Sector, Faculty of Science, Galala University New Galala City 43511 Suez Egypt
| | - Manar T El-Morsy
- Bionanotechnology Department, Faculty of Nanotechnology, Cairo University Giza 12613 Egypt
| | - Habiba Faried
- Biotechnology Department, Faculty of Science, Cairo University Giza 12613 Egypt
| | - Ayah H Diab
- Biotechnology Department, Faculty of Science, Cairo University Giza 12613 Egypt
| | - Shaimaa Shehab
- Biotechnology Department, Faculty of Science, Cairo University Giza 12613 Egypt
| | - Ahmed M Saleh
- Bionanotechnology Department, Faculty of Nanotechnology, Cairo University Giza 12613 Egypt
| | - Gomaa A M Ali
- College of Marine Science and Aquatic Biology, University of Khorfakkan 18119 Sharjah United Arab Emirates
- Faculty of Science, Galala University 43511 Suez Egypt
- Chemistry Department, Faculty of Science, Al-Azhar University Assiut 71524 Egypt
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Ma C, Cheng Z, Tan H, Wang Y, Sun S, Zhang M, Wang J. Nanomaterials: leading immunogenic cell death-based cancer therapies. Front Immunol 2024; 15:1447817. [PMID: 39185425 PMCID: PMC11341423 DOI: 10.3389/fimmu.2024.1447817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 07/24/2024] [Indexed: 08/27/2024] Open
Abstract
The field of oncology has transformed in recent years, with treatments shifting from traditional surgical resection and radiation therapy to more diverse and customized approaches, one of which is immunotherapy. ICD (immunogenic cell death) belongs to a class of regulatory cell death modalities that reactivate the immune response by facilitating the interaction between apoptotic cells and immune cells and releasing specific signaling molecules, and DAMPs (damage-associated molecular patterns). The inducers of ICD can elevate the expression of specific proteins to optimize the TME (tumor microenvironment). The use of nanotechnology has shown its unique potential. Nanomaterials, due to their tunability, targeting, and biocompatibility, have become powerful tools for drug delivery, immunomodulators, etc., and have shown significant efficacy in clinical trials. In particular, these nanomaterials can effectively activate the ICD, trigger a potent anti-tumor immune response, and maintain long-term tumor suppression. Different types of nanomaterials, such as biological cell membrane-modified nanoparticles, self-assembled nanostructures, metallic nanoparticles, mesoporous materials, and hydrogels, play their respective roles in ICD induction due to their unique structures and mechanisms of action. Therefore, this review will explore the latest advances in the application of these common nanomaterials in tumor ICD induction and discuss how they can provide new strategies and tools for cancer therapy. By gaining a deeper understanding of the mechanism of action of these nanomaterials, researchers can develop more precise and effective therapeutic approaches to improve the prognosis and quality of life of cancer patients. Moreover, these strategies hold the promise to overcome resistance to conventional therapies, minimize side effects, and lead to more personalized treatment regimens, ultimately benefiting cancer treatment.
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Affiliation(s)
- Changyu Ma
- Department of Urology, China-Japan Friendship Hospital, Beijing, China
- Graduate School of Peking Union Medical College, Peking Union Medical College, Beijing, China
| | - Zhe Cheng
- Department of Forensic Medicine, Harbin Medical University, Harbin, China
| | - Haotian Tan
- Department of Urology, China-Japan Friendship Hospital, Beijing, China
- Graduate School of Peking Union Medical College, Peking Union Medical College, Beijing, China
| | - Yihan Wang
- Department of Urology, China-Japan Friendship Hospital, Beijing, China
- China-Japan Friendship Clinical College, Peking University Health Science Center, Beijing, China
| | - Shuzhan Sun
- Department of Urology, China-Japan Friendship Hospital, Beijing, China
- China-Japan Friendship Clinical College, Peking University Health Science Center, Beijing, China
| | - Mingxiao Zhang
- Department of Urology, China-Japan Friendship Hospital, Beijing, China
| | - Jianfeng Wang
- Department of Urology, China-Japan Friendship Hospital, Beijing, China
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Xu Z, Zhou Z, Yang X, Thakur A, Han N, Li HT, Li LG, Hu J, Li TF, Yan Y. Determining M2 macrophages content for the anti-tumor effects of metal-organic framework-encapsulated pazopanib nanoparticles in breast cancer. J Nanobiotechnology 2024; 22:429. [PMID: 39033109 PMCID: PMC11264935 DOI: 10.1186/s12951-024-02694-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 07/02/2024] [Indexed: 07/23/2024] Open
Abstract
Pazopanib (PAZ), an oral multi-tyrosine kinase inhibitor, demonstrates promising cytostatic activities against various human cancers. However, its clinical utility is limited by substantial side effects and therapeutic resistance. We developed a nanoplatform capable of delivering PAZ for enhanced anti-breast cancer therapy. Nanometer-sized PAZ@Fe-MOF, compared to free PAZ, demonstrated increased anti-tumor therapeutic activities in both syngeneic murine 4T1 and xenograft human MDA-MB-231 breast cancer models. High-throughput single-cell RNA sequencing (scRNAseq) revealed that PAZ@Fe-MOF significantly reduced pro-tumorigenic M2-like macrophage populations at tumor sites and suppressed M2-type signaling pathways, such as ATF6-TGFBR1-SMAD3, as well as chemokines including CCL17, CCL22, and CCL24. PAZ@Fe-MOF reprogramed the inhibitory immune microenvironment and curbed tumorigenicity by blocking the polarization of M2 phenotype macrophages. This platform offers a promising and new strategy for improving the cytotoxicity of PAZ against breast cancers. It provides a method to evaluate the immunological response of tumor cells to PAZ-mediated treatment.
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Affiliation(s)
- Zhijie Xu
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Shiyan Key Laboratory of Natural Medicine Nanoformulation Research, Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Zhiyang Zhou
- Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Clinical Research Center for Breast Cancer in Hunan Province, Changsha, 410008, Hunan, China
| | - Xiaoxin Yang
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Abhimanyu Thakur
- Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Ning Han
- Shiyan Key Laboratory of Natural Medicine Nanoformulation Research, Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Hai-Tao Li
- Shiyan Key Laboratory of Natural Medicine Nanoformulation Research, Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Liu-Gen Li
- Shiyan Key Laboratory of Natural Medicine Nanoformulation Research, Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Jun Hu
- Shiyan Key Laboratory of Natural Medicine Nanoformulation Research, Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, 442000, Hubei, China.
| | - Tong-Fei Li
- Shiyan Key Laboratory of Natural Medicine Nanoformulation Research, Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, 442000, Hubei, China.
| | - Yuanliang Yan
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
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Hou Y, Zhu C, Ban G, Shen Z, Liang Y, Chen K, Wang C, Shi H. Advancements and Challenges in the Application of Metal-Organic Framework (MOF) Nanocomposites for Tumor Diagnosis and Treatment. Int J Nanomedicine 2024; 19:6295-6317. [PMID: 38919774 PMCID: PMC11198007 DOI: 10.2147/ijn.s463144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 05/21/2024] [Indexed: 06/27/2024] Open
Abstract
Nanoscale metal-organic frameworks (MOFs) offer high biocompatibility, nanomaterial permeability, substantial specific surface area, and well-defined pores. These properties make MOFs valuable in biomedical applications, including biological targeting and drug delivery. They also play a critical role in tumor diagnosis and treatment, including tumor cell targeting, identification, imaging, and therapeutic methods such as drug delivery, photothermal effects, photodynamic therapy, and immunogenic cell death. The diversity of MOFs with different metal centers, organics, and surface modifications underscores their multifaceted contributions to tumor research and treatment. This review is a summary of these roles and mechanisms. The final section of this review summarizes the current state of the field and discusses prospects that may bring MOFs closer to pharmaceutical applications.
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Affiliation(s)
- Yingze Hou
- School of Intelligent Medical Engineering, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China
- Clinical Medical College, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China
| | - Can Zhu
- Department of Urology, The Second Clinical Medical College of Anhui Medical University, Hefei, 230032, People’s Republic of China
| | - Ge Ban
- School of Intelligent Medical Engineering, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China
| | - Zhean Shen
- Heart Center, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, 310000, People’s Republic of China
| | - Yingbing Liang
- Department of Chemistry and Biotechnology, Graduate School of Engineering Tottori University Koyama-Minami 4-101, Tottori, 680-8552, Japan
| | - Kun Chen
- School of Intelligent Medical Engineering, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China
| | - Chenbo Wang
- School of Intelligent Medical Engineering, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China
| | - Heng Shi
- Heart Center, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, 310000, People’s Republic of China
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Wang Y, Xie F, Zhao L. Spatially Confined Nanoreactors Designed for Biological Applications. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2310331. [PMID: 38183369 DOI: 10.1002/smll.202310331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Revised: 12/13/2023] [Indexed: 01/08/2024]
Abstract
The applications of nanoreactors in biology are becoming increasingly significant and prominent. Specifically, nanoreactors with spatially confined, due to their exquisite design that effectively limits the spatial range of biomolecules, attracted widespread attention. The main advantage of this structure is designed to improve reaction selectivity and efficiency by accumulating reactants and catalysts within the chambers, thus increasing the frequency of collisions between reactants. Herein, the recent progress in the synthesis of spatially confined nanoreactors and their biological applications is summarized, covering various kinds of nanoreactors, including porous inorganic materials, porous crystalline materials with organic components and self-assembled polymers to construct nanoreactors. These design principles underscore how precise reaction control could be achieved by adjusting the structure and composition of the nanoreactors to create spatial confined. Furthermore, various applications of spatially confined nanoreactors are demonstrated in the biological fields, such as biocatalysis, molecular detection, drug delivery, and cancer therapy. These applications showcase the potential prospects of spatially confined nanoreactors, offering robust guidance for future research and innovation.
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Affiliation(s)
- Yating Wang
- School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200241, P. R. China
| | - Fengjuan Xie
- School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200241, P. R. China
| | - Liang Zhao
- School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200241, P. R. China
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11
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Han Y, Tian X, Zhai J, Zhang Z. Clinical application of immunogenic cell death inducers in cancer immunotherapy: turning cold tumors hot. Front Cell Dev Biol 2024; 12:1363121. [PMID: 38774648 PMCID: PMC11106383 DOI: 10.3389/fcell.2024.1363121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Accepted: 04/23/2024] [Indexed: 05/24/2024] Open
Abstract
Immunotherapy has emerged as a promising cancer treatment option in recent years. In immune "hot" tumors, characterized by abundant immune cell infiltration, immunotherapy can improve patients' prognosis by activating the function of immune cells. By contrast, immune "cold" tumors are often less sensitive to immunotherapy owing to low immunogenicity of tumor cells, an immune inhibitory tumor microenvironment, and a series of immune-escape mechanisms. Immunogenic cell death (ICD) is a promising cellular process to facilitate the transformation of immune "cold" tumors to immune "hot" tumors by eliciting innate and adaptive immune responses through the release of (or exposure to) damage-related molecular patterns. Accumulating evidence suggests that various traditional therapies can induce ICD, including chemotherapy, targeted therapy, radiotherapy, and photodynamic therapy. In this review, we summarize the biological mechanisms and hallmarks of ICD and introduce some newly discovered and technologically innovative inducers that activate the immune system at the molecular level. Furthermore, we also discuss the clinical applications of combing ICD inducers with cancer immunotherapy. This review will provide valuable insights into the future development of ICD-related combination therapeutics and potential management for "cold" tumors.
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Affiliation(s)
| | | | | | - Zhenyong Zhang
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
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12
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Xu W, Liu W, Yang J, Lu J, Zhang H, Ye D. Stimuli-responsive nanodelivery systems for amplifying immunogenic cell death in cancer immunotherapy. Immunol Rev 2024; 321:181-198. [PMID: 37403660 DOI: 10.1111/imr.13237] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 06/23/2023] [Accepted: 06/26/2023] [Indexed: 07/06/2023]
Abstract
Immunogenic cell death (ICD) is a special pattern of tumor cell death, enabling to elicit tumor-specific immune response via the release of damage-associated molecular patterns and tumor-associated antigens in the tumor microenvironment. ICD-induced immunotherapy holds the promise for completely eliminating tumors and long-term protective antitumor immune response. Increasing ICD inducers have been discovered for boosting antitumor immunity via evoking ICD. Nonetheless, the utilization of ICD inducers remains insufficient owing to serious toxic reactions, low localization efficiency within the tumor microenvironmental niche, etc. For overcoming such limitations, stimuli-responsive multifunctional nanoparticles or nanocomposites with ICD inducers have been developed for improving immunotherapeutic efficiency via lowering toxicity, which represent a prospective scheme for fostering the utilization of ICD inducers in immunotherapy. This review outlines the advances in near-infrared (NIR)-, pH-, redox-, pH- and redox-, or NIR- and tumor microenvironment-responsive nanodelivery systems for ICD induction. Furthermore, we discuss their clinical translational potential. The progress of stimuli-responsive nanoparticles in clinical settings depends upon the development of biologically safer drugs tailored to patient needs. Moreover, an in-depth comprehending of ICD biomarkers, immunosuppressive microenvironment, and ICD inducers may accelerate the advance in smarter multifunctional nanodelivery systems to further amplify ICD.
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Affiliation(s)
- Wenhao Xu
- Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
- Shanghai Genitourinary Cancer Institute, Shanghai, China
| | - Wangrui Liu
- Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jianfeng Yang
- Department of Surgery, ShangNan Branch of Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jiahe Lu
- Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
- Shanghai Genitourinary Cancer Institute, Shanghai, China
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK
| | - Hailiang Zhang
- Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
- Shanghai Genitourinary Cancer Institute, Shanghai, China
| | - Dingwei Ye
- Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
- Shanghai Genitourinary Cancer Institute, Shanghai, China
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Ma D, Wang G, Lu J, Zeng X, Cheng Y, Zhang Z, Lin N, Chen Q. Multifunctional nano MOF drug delivery platform in combination therapy. Eur J Med Chem 2023; 261:115884. [PMID: 37862817 DOI: 10.1016/j.ejmech.2023.115884] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Revised: 10/11/2023] [Accepted: 10/14/2023] [Indexed: 10/22/2023]
Abstract
Recent preclinical and clinical studies have demonstrated that for cancer treatment, combination therapies are more effective than monotherapies in reducing drug-related toxicity, decreasing drug resistance, and improving therapeutic efficacy. With the rapid development of nanotechnology, the combination of metal-organic frameworks (MOFs) and multi-mode therapy offers a realistic possibility to further improve the shortcomings of cancer treatment. This article focuses on the latest developments, achievements, and treatment strategies of representative multifunctional MOF combination therapies for cancer treatment in recent years, which include not only bimodal combination therapies, but also multi-modal synergistic therapies, further demonstrating the effectiveness and superiority of the MOF drug delivery systems in cancer treatment.
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Affiliation(s)
- Dongwei Ma
- Guangxi Scientific Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, 530200, China; Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Nanning, 530200, China
| | - Gang Wang
- Guangxi Scientific Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, 530200, China; Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Nanning, 530200, China
| | - Jingsheng Lu
- Guangxi Scientific Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, 530200, China; Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Nanning, 530200, China
| | - Xiaoxuan Zeng
- Guangxi Scientific Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, 530200, China; Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Nanning, 530200, China
| | - Yanwei Cheng
- Guangxi Scientific Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, 530200, China; Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Nanning, 530200, China
| | - Zhenwei Zhang
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530200, China; Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Nanning, 530200, China
| | - Ning Lin
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530200, China; Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Nanning, 530200, China.
| | - Qing Chen
- Guangxi Scientific Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, 530200, China; Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Nanning, 530200, China.
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Wu Y, Wang R, Shen P, Zhou W, Chen C, Yang K, Yang J, Song Y, Han X, Guan X. Boosting immunogenic cell death via hollow MnO2-based multiple stimuli-responsive drug delivery systems for improved cancer immunotherapy. Cancer Nanotechnol 2023. [DOI: 10.1186/s12645-023-00173-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/13/2023] Open
Abstract
AbstractCancer treatment by inducing tumor cell immunogenic cell death (ICD) is critical for tumor therapy. However, ICD activation by single pathway is often limited in practical application due to its low efficiency. In addition, the low pH and anoxic microenvironments in solid tumors greatly limit the effective activation of ICD. Herein, hollow manganese dioxide (H-MnO2) nanomaterials were selected to load both Mitoxantrone (MTZ) and Chlorin e6 (Ce6) due to its hollow structure and ability to release drugs in the acidic environments. Thus, the synergy of photodynamic therapy (PDT), photothermal therapy (PTT) and chemotherapy can induce the process of immunogenic cell death, stimulate the maturation of dendritic cells (DCs), and activate the immune response to kill tumor cells dramatically. Efficient immunotherapeutic effects were obtained when MnO2-C/M-HA was given intravenously to 4T1 tumor-bearing BALB/c mice with 660 nm near-infrared laser irradiation. This study overcame the limitations of monotherapy and provided a multifunctional platform for tumor immunotherapy.
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Padya BS, Fernandes G, Hegde S, Kulkarni S, Pandey A, Deshpande PB, Ahmad SF, Upadhya D, Mutalik S. Targeted Delivery of 5-Fluorouracil and Sonidegib via Surface-Modified ZIF-8 MOFs for Effective Basal Cell Carcinoma Therapy. Pharmaceutics 2023; 15:2594. [PMID: 38004573 PMCID: PMC10675485 DOI: 10.3390/pharmaceutics15112594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 10/23/2023] [Accepted: 10/30/2023] [Indexed: 11/26/2023] Open
Abstract
The therapeutic effectiveness of the most widely used anticancer drug 5-fluorouracil (5-FU) is constrained by its high metabolism, short half-life, and rapid drug resistance after chemotherapy. Although various nanodrug delivery systems have been reported for skin cancer therapy, their retention, penetration and targeting are still a matter of concern. Hence, in the current study, a topical gel formulation that contains a metal-organic framework (zeolitic imidazole framework; ZIF-8) loaded with 5-FU and a surface modified with sonidegib (SDG; acting as a therapeutic agent as well as a targeting ligand) (5-FU@ZIF-8 MOFs) is developed against DMBA-UV-induced BCC skin cancer in rats. The MOFs were prepared using one-pot synthesis followed by post drug loading and SDG conjugation. The optimized MOFs were incorporated into hyaluronic acid-hydroxypropyl methyl cellulose gel and further subjected to characterization. Enhanced skin deposition of the 5-FU@ZIF-8-SDG MOFs was observed using ex vivo skin permeation studies. Confocal laser microscopy studies showed that 5-FU@ZIF-8-SDG MOFs permeated the skin via the transfollicular pathway. The 5-FU@ZIF-8-SDG MOFs showed stronger cell growth inhibition in A431 cells and good biocompatibility with HaCaT cells. Histopathological studies showed that the efficacy of the optimized MOF gels improved as the epithelial cells manifested modest hyperplasia, nuclear pleomorphism, and dyskeratosis. Additionally, immunohistochemistry and protein expression studies demonstrated the improved effectiveness of the 5-FU@ZIF-8-SDG MOFs, which displayed a considerable reduction in the expression of Bcl-2 protein. Overall, the developed MOF gels showed good potential for the targeted delivery of multifunctional MOFs in topical formulations for treating BCC cancer.
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Affiliation(s)
- Bharath Singh Padya
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India; (B.S.P.); (G.F.); (S.K.); (A.P.)
- Department of Pharmaceutics Sciences, Vignan Foundation for Science, Technology and Research, Vadlamudi, Guntur 522213, Andhra Pradesh, India
| | - Gasper Fernandes
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India; (B.S.P.); (G.F.); (S.K.); (A.P.)
| | - Sumukha Hegde
- Centre for Molecular Neurosciences, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India; (S.H.); (D.U.)
| | - Sanjay Kulkarni
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India; (B.S.P.); (G.F.); (S.K.); (A.P.)
| | - Abhijeet Pandey
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India; (B.S.P.); (G.F.); (S.K.); (A.P.)
| | - Praful Balavant Deshpande
- Respiratory R&D, Teva Pharmaceuticals Ireland, Unit 301, IDA Business Park, X91 WK68 Waterford, Ireland;
| | - Sheikh F. Ahmad
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;
| | - Dinesh Upadhya
- Centre for Molecular Neurosciences, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India; (S.H.); (D.U.)
| | - Srinivas Mutalik
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India; (B.S.P.); (G.F.); (S.K.); (A.P.)
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16
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Chafiq M, Chaouiki A, Ko YG. Recent Advances in Multifunctional Reticular Framework Nanoparticles: A Paradigm Shift in Materials Science Road to a Structured Future. NANO-MICRO LETTERS 2023; 15:213. [PMID: 37736827 PMCID: PMC10516851 DOI: 10.1007/s40820-023-01180-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 07/25/2023] [Indexed: 09/23/2023]
Abstract
Porous organic frameworks (POFs) have become a highly sought-after research domain that offers a promising avenue for developing cutting-edge nanostructured materials, both in their pristine state and when subjected to various chemical and structural modifications. Metal-organic frameworks, covalent organic frameworks, and hydrogen-bonded organic frameworks are examples of these emerging materials that have gained significant attention due to their unique properties, such as high crystallinity, intrinsic porosity, unique structural regularity, diverse functionality, design flexibility, and outstanding stability. This review provides an overview of the state-of-the-art research on base-stable POFs, emphasizing the distinct pros and cons of reticular framework nanoparticles compared to other types of nanocluster materials. Thereafter, the review highlights the unique opportunity to produce multifunctional tailoring nanoparticles to meet specific application requirements. It is recommended that this potential for creating customized nanoparticles should be the driving force behind future synthesis efforts to tap the full potential of this multifaceted material category.
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Affiliation(s)
- Maryam Chafiq
- Materials Electrochemistry Group, School of Materials Science and Engineering, Yeungnam University, Gyeongsan, 38541, Republic of Korea
| | - Abdelkarim Chaouiki
- Materials Electrochemistry Group, School of Materials Science and Engineering, Yeungnam University, Gyeongsan, 38541, Republic of Korea.
| | - Young Gun Ko
- Materials Electrochemistry Group, School of Materials Science and Engineering, Yeungnam University, Gyeongsan, 38541, Republic of Korea.
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Su D, Zhang Z, Xia F, Liang Q, Liu Y, Liu W, Xu Z. ICD-related risk model predicts the prognosis and immunotherapy response of patients with liver cancer. Front Pharmacol 2023; 14:1202823. [PMID: 37361216 PMCID: PMC10285067 DOI: 10.3389/fphar.2023.1202823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 05/30/2023] [Indexed: 06/28/2023] Open
Abstract
Immunogenic cell death (ICD) is a novel cell death mechanism that activates and regulates the immune system against cancer. However, its prognostic value in liver cancer remains unclear. Here, several algorithms such as correlation analysis, Cox regression analysis, and Lasso regression analysis were carried out to evaluate the prognostic value of ICD-related genes in patients with liver cancer. Three ICD-related prognostic genes, the prion protein gene (PRNP), dynamin 1-like gene (DNM1L), and caspase-8 (CASP8), were identified and used to construct a risk signature. Patients with liver cancer were categorized into high- and low-risk groups using the ICD-related signature. Subsequently, a multivariate regression analysis revealed that the signature was an independent risk factor in liver cancer [hazard ratio (HR) = 6.839; 95% confidence interval (CI) = 1.625-78.785]. Patient survival was also predicted using the risk model, with area under the curve values of 0.75, 0.70, and 0.69 for 1-, 3-, and 5-year survival, respectively. Finally, a prognostic nomogram containing the clinical characteristics and risk scores of patients was constructed. The constructed ICD-related signature could serve as a prognostic and immunotherapeutic biomarker in liver cancer.
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Affiliation(s)
- Duntao Su
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zeyu Zhang
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Fada Xia
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Qiuju Liang
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yuanhong Liu
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Wei Liu
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zhijie Xu
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China
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18
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Yang M, Zhang C, Wang R, Wu X, Li H, Yoon J. Cancer Immunotherapy Elicited by Immunogenic Cell Death Based on Smart Nanomaterials. SMALL METHODS 2023; 7:e2201381. [PMID: 36609838 DOI: 10.1002/smtd.202201381] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 12/13/2022] [Indexed: 05/17/2023]
Abstract
Cancer immunotherapy has been a revolutionary cancer treatment modality because it can not only eliminate primary tumors but also prevent metastases and recurrent tumors. Immunogenic cell death (ICD) induced by various treatment modalities, including chemotherapy, phototherapy, and radiotherapy, converts dead cancer cells into therapeutic vaccines, eliciting a systemic antigen-specific antitumor. However, the outcome effect of cancer immunotherapy induced by ICD has been limited due to the low accumulation efficiency of ICD inducers in the tumor site and concomitant damage to normal tissues. The boom in smart nanomaterials is conducive to overcoming these hurdles owing to their virtues of good stability, targeted lesion site, high bioavailability, on-demand release, and good biocompatibility. Herein, the design of targeted nanomaterials, various ICD inducers, and the applications of nanomaterials responsive to different stimuli, including pH, enzymes, reactive oxygen species, or dual responses are summarized. Furthermore, the prospect and challenges are briefly outlined to provide reference and inspiration for designing novel smart nanomaterials for immunotherapy induced by ICD.
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Affiliation(s)
- Mengyao Yang
- Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, 03760, Republic of Korea
| | - Cheng Zhang
- State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, Dalian, 116024, China
- School of Bioengineering, Dalian University of Technology, Dalian, 116024, China
| | - Rui Wang
- Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, 03760, Republic of Korea
| | - Xiaofeng Wu
- Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, 03760, Republic of Korea
| | - Haidong Li
- State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, Dalian, 116024, China
- School of Bioengineering, Dalian University of Technology, Dalian, 116024, China
| | - Juyoung Yoon
- Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, 03760, Republic of Korea
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Tian J, Wang J, Xu H, Zou B, Chen W, Liu Y, Chen J, Zhang R. Nanoscale metal-organic framework delivers rapamycin to induce tissue immunogenic cell death and potentiates cancer immunotherapy. NANOMEDICINE : NANOTECHNOLOGY, BIOLOGY, AND MEDICINE 2023; 50:102678. [PMID: 37044194 DOI: 10.1016/j.nano.2023.102678] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 03/21/2023] [Accepted: 04/02/2023] [Indexed: 04/14/2023]
Abstract
Rapamycin has great potential in the antitumor application, but its therapeutic effect is seriously affected by poor water solubility, targeting ability, and low bioavailability. Here, we constructed a novel composite nanomaterial with PCN-224 as a drug carrier and loaded rapamycin, named R@BP@HA. The nanoplate not only improves targeting, but also synergizes rapamycin with PCN-224 to effectively promote tumor cell apoptosis, which subsequently causes immunogenic cell death (ICD), and shows strong therapeutic effect in 4T1 breast cancer model. The treatment effect depends on three main points:(i)Proapoptotic effect of rapamycin on tumor cells;(ii)ROS production by PCN-224-mediated photodynamic therapy;(iii)ICD induced DC maturation, increased immune response and promoted T cell proliferation and differentiation. This nanoplate offers potential antitumor efficacy in combination with chemotherapy, photodynamic therapy, and immunotherapy.
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Affiliation(s)
- Jihua Tian
- Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan 030001, China.
| | - Jing Wang
- Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan 030001, China
| | - Huanyu Xu
- Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan 030001, China
| | - Bocheng Zou
- Department of The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032, China
| | - Weihao Chen
- Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan 030001, China
| | - Yulong Liu
- Department of The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032, China
| | - Jingshu Chen
- Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan 030001, China
| | - Ruiping Zhang
- Department of The Radiology Department of First Hospital of Shanxi Medical University, Taiyuan 030001, China.
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Mosqueira VCF, Machado MGC, de Oliveira MA. Polymeric Nanocarriers in Cancer Theranostics. Cancer Nanotechnol 2023. [DOI: 10.1007/978-3-031-17831-3_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
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21
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Ding YN, Xue M, Tang QS, Wang LJ, Ding HY, Li H, Gao CC, Yu WP. Immunotherapy-based novel nanoparticles in the treatment of gastrointestinal cancer: Trends and challenges. World J Gastroenterol 2022; 28:5403-5419. [PMID: 36312831 PMCID: PMC9611702 DOI: 10.3748/wjg.v28.i37.5403] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 08/27/2022] [Accepted: 09/15/2022] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal cancer (GIC) is the most common cancer with a poor prognosis. Currently, surgery is the main treatment for GIC. However, the high rate of postoperative recurrence leads to a low five-year survival rate. In recent years, immunotherapy has received much attention. As the only immunotherapy drugs approved by the Food and Drug Administration (FDA), immune checkpoint blockade (ICB) drugs have great potential in cancer therapy. Nevertheless, the efficacy of ICB treatment is greatly limited by the low immunogenicity and immunosuppressive microenvironment of GIC. Therefore, the targets of immunotherapy have expanded from ICB to increasing tumor immunogenicity, increasing the recruitment and maturation of immune cells and reducing the proportion of inhibitory immune cells, such as M2-like macrophages, regulatory T cells and myeloid-derived suppressor cells. Moreover, with the development of nanotechnology, a variety of nanoparticles have been approved by the FDA for clinical therapy, so novel nanodrug delivery systems have become a research focus for anticancer therapy. In this review, we summarize recent advances in the application of immunotherapy-based nanoparticles in GICs, such as gastric cancer, hepatocellular carcinoma, colorectal cancer and pancreatic cancer, and described the existing challenges and future trends.
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Affiliation(s)
- Yi-Nan Ding
- Department of Pathophysiology, College of Medicine, Southeast University, Nanjing 210000, Jiangsu Province, China
| | - Ming Xue
- Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210000, Jiangsu Province, China
| | - Qiu-Sha Tang
- Department of Pathophysiology, College of Medicine, Southeast University, Nanjing 210000, Jiangsu Province, China
| | - Li-Jun Wang
- Department of Pathophysiology, College of Medicine, Southeast University, Nanjing 210000, Jiangsu Province, China
| | - Hui-Yan Ding
- Department of Pathophysiology, College of Medicine, Southeast University, Nanjing 210000, Jiangsu Province, China
| | - Han Li
- Department of Tuberculosis, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu Province, China
| | - Cheng-Cheng Gao
- Department of Radiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
| | - Wei-Ping Yu
- Medical School, Southeast University, Nanjing 210009, Jiangsu Province, China
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