Tumor microenvironment-responsive nanoplatforms for enhanced cancer immunotherapy: Advances and synergistic strategies
Despite remarkable advancements in cancer immunotherapy, its clinical efficacy remains constrained by challenges including insufficient tumor accumulation of immunotherapeutics, limited patient response rates, and immune-related adverse events. Tumor microenvironment (TME)-responsive nanoplatforms h...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2025-12-01
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| Series: | Nano TransMed |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2790676025000238 |
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| author | Jie Wu Xiangdong Xue Haijing Qu |
| author_facet | Jie Wu Xiangdong Xue Haijing Qu |
| author_sort | Jie Wu |
| collection | DOAJ |
| description | Despite remarkable advancements in cancer immunotherapy, its clinical efficacy remains constrained by challenges including insufficient tumor accumulation of immunotherapeutics, limited patient response rates, and immune-related adverse events. Tumor microenvironment (TME)-responsive nanoplatforms have emerged as a promising strategy to address these limitations, which could respond to endogenous signals in tumor cells to achieve precise targeting, controlled drug release, and reversal of tumor immunosuppressive microenvironments. Herein, this article systematically reviews TME-responsive design strategies based on intrinsic tumor-specific features, including acidic pH, elevated reactive oxygen species (ROS) levels, reductive conditions, hypoxia, and overexpressed enzymes. Furthermore, we elucidate synergistic mechanisms of TME-responsive nanosystems empowering immunotherapy: i) subcellular organelle-specific delivery, ii) TME remodeling, iii) immunometabolic reprogramming and iv) lymph node drainage regulation. Finally, the current challenges and future directions for clinical translation of these advanced nanomedicine-based immunotherapeutic strategies are discussed, providing insights for the development of next-generation cancer immunotherapies. |
| format | Article |
| id | doaj-art-d415d591856d4c27a45a1cbb9609d3ec |
| institution | Kabale University |
| issn | 2790-6760 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Nano TransMed |
| spelling | doaj-art-d415d591856d4c27a45a1cbb9609d3ec2025-08-20T03:27:52ZengKeAi Communications Co., Ltd.Nano TransMed2790-67602025-12-01410009210.1016/j.ntm.2025.100092Tumor microenvironment-responsive nanoplatforms for enhanced cancer immunotherapy: Advances and synergistic strategiesJie Wu0Xiangdong Xue1Haijing Qu2Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, ChinaShanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, ChinaCorresponding author.; Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, ChinaDespite remarkable advancements in cancer immunotherapy, its clinical efficacy remains constrained by challenges including insufficient tumor accumulation of immunotherapeutics, limited patient response rates, and immune-related adverse events. Tumor microenvironment (TME)-responsive nanoplatforms have emerged as a promising strategy to address these limitations, which could respond to endogenous signals in tumor cells to achieve precise targeting, controlled drug release, and reversal of tumor immunosuppressive microenvironments. Herein, this article systematically reviews TME-responsive design strategies based on intrinsic tumor-specific features, including acidic pH, elevated reactive oxygen species (ROS) levels, reductive conditions, hypoxia, and overexpressed enzymes. Furthermore, we elucidate synergistic mechanisms of TME-responsive nanosystems empowering immunotherapy: i) subcellular organelle-specific delivery, ii) TME remodeling, iii) immunometabolic reprogramming and iv) lymph node drainage regulation. Finally, the current challenges and future directions for clinical translation of these advanced nanomedicine-based immunotherapeutic strategies are discussed, providing insights for the development of next-generation cancer immunotherapies.http://www.sciencedirect.com/science/article/pii/S2790676025000238Cancer immunotherapyTumor microenvironmentResponsive nanoplatforms |
| spellingShingle | Jie Wu Xiangdong Xue Haijing Qu Tumor microenvironment-responsive nanoplatforms for enhanced cancer immunotherapy: Advances and synergistic strategies Nano TransMed Cancer immunotherapy Tumor microenvironment Responsive nanoplatforms |
| title | Tumor microenvironment-responsive nanoplatforms for enhanced cancer immunotherapy: Advances and synergistic strategies |
| title_full | Tumor microenvironment-responsive nanoplatforms for enhanced cancer immunotherapy: Advances and synergistic strategies |
| title_fullStr | Tumor microenvironment-responsive nanoplatforms for enhanced cancer immunotherapy: Advances and synergistic strategies |
| title_full_unstemmed | Tumor microenvironment-responsive nanoplatforms for enhanced cancer immunotherapy: Advances and synergistic strategies |
| title_short | Tumor microenvironment-responsive nanoplatforms for enhanced cancer immunotherapy: Advances and synergistic strategies |
| title_sort | tumor microenvironment responsive nanoplatforms for enhanced cancer immunotherapy advances and synergistic strategies |
| topic | Cancer immunotherapy Tumor microenvironment Responsive nanoplatforms |
| url | http://www.sciencedirect.com/science/article/pii/S2790676025000238 |
| work_keys_str_mv | AT jiewu tumormicroenvironmentresponsivenanoplatformsforenhancedcancerimmunotherapyadvancesandsynergisticstrategies AT xiangdongxue tumormicroenvironmentresponsivenanoplatformsforenhancedcancerimmunotherapyadvancesandsynergisticstrategies AT haijingqu tumormicroenvironmentresponsivenanoplatformsforenhancedcancerimmunotherapyadvancesandsynergisticstrategies |