TUMOR MICROENVIRONMENT-RESPONSIVE NANOMEDICINE FOR ENHANCED CANCER THERAPEUTICS
Indonesia 
Malaysia Malaysia 
Article Sidebar
-
Cancer Therapeutics, Multidrug Resistance, Nanomedicine, Targeted Drug Delivery, Tumor Microenvironment
Abstract
The tumor microenvironment (TME) plays a critical role in cancer progression, drug resistance, and metastasis. As a result, targeting the TME with nanomedicine has become a promising strategy to enhance the efficacy of cancer therapeutics. This research explores the development of tumor microenvironment-responsive nanomedicine as a means to selectively deliver therapeutic agents to the tumor site, thus minimizing off-target effects and improving therapeutic outcomes. The primary goal of this study is to design and evaluate nanomedicine systems that can respond to specific factors within the TME, such as pH, enzymes, and hypoxia. The study employs a combination of in vitro and in vivo techniques, including cellular assays, animal models, and advanced imaging techniques, to assess the response of the nanomedicine to the tumor microenvironment and its therapeutic efficacy. The results indicate that the tumor microenvironment-responsive nanomedicine significantly enhances drug delivery, improving tumor targeting and reducing systemic toxicity. Furthermore, the nanomedicine shows a remarkable ability to overcome multidrug resistance, making it a promising candidate for enhancing the effectiveness of existing cancer therapies. In conclusion, tumor microenvironment-responsive nanomedicine presents a novel and effective strategy for cancer treatment, offering a targeted approach that holds potential for improved therapeutic outcomes in cancer patients.
Full text article
References
Abdellatif, A. A. H., Bouazzaoui, A., Tawfeek, H. M., & Younis, M. A. (2024). MCT4 knockdown by tumor microenvironment-responsive nanoparticles remodels the cytokine profile and eradicates aggressive breast cancer cells. Colloids and Surfaces B: Biointerfaces, 238, 113930. https://doi.org/10.1016/j.colsurfb.2024.113930
Bhoi, S., Ramraje, G., Ahire, N., & Patil, V. (2026). Bridging the gap in nanomedicine: Translational challenges and innovations in stimuli-responsive nanocarriers. Nano-Structures & Nano-Objects, 46, 101652. https://doi.org/10.1016/j.nanoso.2026.101652
Deng, X., Liu, X., & Zhao, L. (2025). Multifunctional nanoplatforms for tumor microenvironment remodeling: Toward precision and intelligent cancer therapy. Materials Today Bio, 35, 102385. https://doi.org/10.1016/j.mtbio.2025.102385
Fu, X., Zhang, H., Liu, W., Wu, T., & Zheng, Y. (2026). Hypoxia-responsive self-assembled nanoparticles for reprogramming tumor-associated macrophages into an anti-tumor M1 phenotype in breast cancer. Materials Today Bio, 37, 102956. https://doi.org/10.1016/j.mtbio.2026.102956
Girma, W. M., Mekuria, S. L., Gedda, G., Shi, X., Park, Y.-J., & Pang, M.-G. (2026). Carbon dot-based nanohybrids for tumor microenvironment-activated cancer theranostics. Coordination Chemistry Reviews, 548, 217236. https://doi.org/10.1016/j.ccr.2025.217236
Gore, S., Are, V., Chanchlani, B., Shishira, PS., & Biswas, S. (2025). Multifunctional nanoplatforms for combined photothermal and photodynamic therapy: Tumor-responsive strategies for enhanced precision. International Journal of Pharmaceutics, 684, 126131. https://doi.org/10.1016/j.ijpharm.2025.126131
Guo, F., & Pan, Y. (2025). Targeting lung cancer utilizing smart nanoparticles: Nanomedicine meets tumor stroma. Bioorganic Chemistry, 167, 109202. https://doi.org/10.1016/j.bioorg.2025.109202
Hai, L., Wang, J., Liu, D., Yun, K., Ma, K., Peng, Y., Xu, M., Ma, X., Gao, S., Wang, Q., Zhou, J., Liang, S., & Wang, Z. (2026). Tumor-responsive nanoparticles precisely overcome hypoxia-mediated STING dysfunction to unleash potent antitumor immunity. Acta Pharmaceutica Sinica B. https://doi.org/10.1016/j.apsb.2026.06.043
Hasannia, M., Abounoori, M., Mahmoudian, F., Rahdar, A., Fathi-karkan, S., Shirzad, M., & Pandey, S. (2026). Multifunctional Pluronic nanomedicine: Bridging the gap between chemoresistance and effective cancer therapy. Journal of Drug Delivery Science and Technology, 120, 108220. https://doi.org/10.1016/j.jddst.2026.108220
Hou, H., & Li, X. (2026). Design of a pH-Responsive Cu-Doped nanoplatform for Down-Regulating HIF-1? and enhancing Esophageal cancer chemotherapy. Materials & Design, 265, 115981. https://doi.org/10.1016/j.matdes.2026.115981
Hussain, Z., Abdulelah, A. A., Tahseen, S. H., Mashkoor, A. A., & Thu, H. E. (2026). Stimuli-responsive nanomedicines for lung cancer therapy: Design strategies, advances, challenges, and future directions. Journal of Drug Delivery Science and Technology, 116, 107900. https://doi.org/10.1016/j.jddst.2025.107900
Kar, N. P., Lin, J., HassankhaniRad, A., Li, W., Aboushanab, A. R., Li, Y., & Sun, J. (2025). Smart polymeric nanoparticles for targeted delivery and microenvironment-responsive therapy in pancreatic cancer. Smart Materials in Medicine, 6(3), 368–386. https://doi.org/10.1016/j.smaim.2025.09.003
Kawuribi, V., Xie, Y., Xu, H., Zhang, Y., & Zheng, S. (2025). Nano-omics and nanomedicine target microbial carcinogenesis: Tumor microenvironment reprograming to clinical translation. Critical Reviews in Oncology/Hematology, 213, 104866. https://doi.org/10.1016/j.critrevonc.2025.104866
Li, X.-Y., Chen, Y., Liu, J., Wu, X., Wang, C., Yao, M., Li, X., & Huang, J.-D. (2026). Tumor-associated stimuli-responsive sonosensitizers for precise sonodynamic therapy. Coordination Chemistry Reviews, 567, 218313. https://doi.org/10.1016/j.ccr.2026.218313
Li, Z., Ren, G., Wang, X., Li, X., Ding, L., Zhu, J., Zhang, Y., Zhang, C., Zou, J., & Chen, X. (2025). Tumor microenvironment responsive nano-PROTAC for BRD4 degradation enhanced cancer photo-immunotherapy. Biomaterials, 322, 123387. https://doi.org/10.1016/j.biomaterials.2025.123387
Lin, G., Du, K., Landrowski, D., Price, R. J., & Scott, E. A. (2025). Ultrasound-responsive nanoparticles: Modulating the tumor microenvironment to advance cancer immunotherapy. Cell Biomaterials, 1(11), 100255. https://doi.org/10.1016/j.celbio.2025.100255
Lin, H., Liu, Y., Liu, Z., Luo, Y., Wang, C., Ding, Y., Huang, Z., & Zhao, C. (2026). In situ generation of copper complex and multivalent CXCR4 inhibitor via ROS-responsive nanoplatform suppresses breast cancer metastasis. Acta Pharmaceutica Sinica B. https://doi.org/10.1016/j.apsb.2026.05.010
Liu, W., Sun, C., Dai, Y., Wang, H., Ashrafizadeh, M., Conde, J., Yang, L., & He, W. (2025). A tumor microenvironment-responsive Zr-MOF nanosystem for co-delivering siHIF-1? and triptolide enhances photodynamic therapy in esophageal cancer by amplifying ROS generation and reversing hypoxia. Materials Today Bio, 34, 102183. https://doi.org/10.1016/j.mtbio.2025.102183
Molina Diaz, B. I., Zhuang, P., Pan, X., Doctsch, G., & He, M. (2026). Engineering stimuli-responsive extracellular vesicles for enhanced anticancer therapeutics. Current Opinion in Biomedical Engineering, 37, 100634. https://doi.org/10.1016/j.cobme.2025.100634
Mousavi, S. M., Kalashgrani, M. Y., Yang, C.-J., Neralla, V. R., & Lai, J.-Y. (2026). Stimuli-responsive, prodrug-activating enzyme-functionalized metal-organic frameworks for cancer therapy and tumor microenvironment modulation. Coordination Chemistry Reviews, 561, 217943. https://doi.org/10.1016/j.ccr.2026.217943
Oyebade, A., Hossain, M. R., Hasan, M., Oluremi, A., Rahman, M. S., Ali, N., Griffin, R. J., Oyelere, A. K., & Siraj, N. (2026). Macrocyclic histone deacetylase inhibitor-based near-infrared-responsive ionic nanomedicines for enhanced cancer therapy. International Journal of Pharmaceutics, 700, 127045. https://doi.org/10.1016/j.ijpharm.2026.127045
Palva, R. S., Parikh, J. R., Suthar, R. M., Saiyed, M., Patel, M., Prajapati, P., & Shah, U. H. (2025). ECM-responsive PEGylated liposomal biomaterial for enhanced tumor penetration through Dual-Mechanism microenvironment remodeling in lung cancer. International Journal of Pharmaceutics, 681, 125805. https://doi.org/10.1016/j.ijpharm.2025.125805
Sahu, K., Firdous, A., Raza, M. A., Saoji, S. D., Patravale, V. B., & Ajazuddin. (2025). Enzyme-responsive natural nanocarriers for RNA delivery in the tumor microenvironment: A comprehensive review. Journal of Drug Delivery Science and Technology, 114, 107455. https://doi.org/10.1016/j.jddst.2025.107455
Sahu, P., & Satapathy, T. (2026). Liver targeted nanomedicine for treatment of fibrosis and hepatocellular carcinoma: Emerging strategies in ligand-guided, stimuli-responsive and gene-based delivery. Journal of Drug Delivery Science and Technology, 116, 107935. https://doi.org/10.1016/j.jddst.2025.107935
Shu, H., Sia, C. S., Tiang, S. S. L., Goh, B.-H., Low, Y. J., Tey, B. T., & Low, L. E. (2026). Tumor responsive nanoplatforms for TME modulation: From extracellular matrix to intracellular organelles. Journal of Drug Delivery Science and Technology, 120, 108211. https://doi.org/10.1016/j.jddst.2026.108211
Ta, Y.-N. N., Wang, S.-N., & Chen, Y. (2026). Enzyme-based nanomedicine for tumor microenvironment modulation in cancer therapy. Journal of Controlled Release, 396, 115101. https://doi.org/10.1016/j.jconrel.2026.115101
Wang, W., Liu, X., Yan, Z., Yan, K., Zhou, M., Yang, Y., & Yu, H. (2026). Tumor microenvironment activatable immunomodulator for cancer immunotherapy. Journal of Controlled Release, 395, 114949. https://doi.org/10.1016/j.jconrel.2026.114949
Wei, Y., Weng, X., Wang, Y., & Yang, W. (2024). Stimuli-Responsive Polymersomes: Reshaping the Immunosuppressive Tumor Microenvironment. Biomacromolecules, 25(8), 4663–4676. https://doi.org/10.1021/acs.biomac.4c00706
Yang, B., Li, L., An, M., Zhang, B., Yang, Y., Lin, A., Wang, Y., Niu, J., Xiao, P., & Shi, Y. (2026). A tumor-microenvironment-responsive nanoplatform for synergistic chemo-photothermal-photodynamic therapy of hepatocellular carcinoma. Journal of Drug Delivery Science and Technology, 124, 108633. https://doi.org/10.1016/j.jddst.2026.108633
Yao, J., Liu, L., Teng, X., Chu, D., Ding, S., Li, H., Chang, H., & Liu, J. (2026). Bioinspired and stimuli-responsive nanocomposites for targeted therapy in ovarian and endometrial tumors. International Journal of Pharmaceutics: X, 11, 100493. https://doi.org/10.1016/j.ijpx.2026.100493
Younas, A., Wang, S., Asad, M., Al Mamun, A., Majeed, S., Sharif, A., Zhou, Q., Liu, Y., Geng, P., Shao, C., & Xiao, J. (2026). Recent advances in cancer nanomedicine: From smart targeting to personalized therapeutics—Pioneering a new era in precision oncology. Materials Today Bio, 36, 102660. https://doi.org/10.1016/j.mtbio.2025.102660
Yu, Y., Tian, S., Liu, Y., Zhang, Y., Bekish, Y. N., Fomich, M. A., Akhlamionak, T. P., Korotina, U. R., Samailovich, Y. M., Shmanai, V. V., & Shi, K. (2026). Engineered functional nanotherapeutics for remodeling hypoxia in the tumor microenvironment: Toward enhanced cancer therapy. Chinese Chemical Letters, 112644. https://doi.org/10.1016/j.cclet.2026.112644
Zheng, Z., Sun, L., Li, Y., Wang, S., Wang, P., Qiu, S., Tian, Y., & Chen, H. (2025). Gelatin-dopamine-based dual-responsive nanogels for tumor-targeted bortezomib delivery: Minimizing systemic toxicity and enhancing breast cancer therapy. International Journal of Biological Macromolecules, 318, 145084. https://doi.org/10.1016/j.ijbiomac.2025.145084
Zheng, Z., Wu, Y., Chen, Y., Sun, X., Kayitmazer, A. B., Ahmad, A., Ramzan, N., Rafique, M. S., Zhou, X., & Xu, Y. (2025). Engineering stable multi-component pH responsive nanomedicine for enhanced photothermal/photodynamic therapy. Chinese Journal of Chemical Engineering, 81, 32–44. https://doi.org/10.1016/j.cjche.2024.07.028
Zhou, J.-J., Feng, Y.-C., Song, C.-Y., Fan, Y.-T., Wang, G.-Q., & Zhao, X.-B. (2026). Cuproptosis meets sonodynamics: A nanomedicine platform for multimodal cancer therapy. RSC Advances, 16(22), 19636–19656. https://doi.org/10.1039/d6ra01867j
Zhu, Y., Wang, Q., Zheng, Y., Chen, N., Kou, L., & Yao, Q. (2025). Microenvironment responsive nanomedicine for acute pancreatitis treatment. Colloids and Surfaces B: Biointerfaces, 251, 114633. https://doi.org/10.1016/j.colsurfb.2025.114633
Authors
Copyright (c) 2026 Muntasir Muntasir, Amin Zaki, Faisal Razak
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
