Polymeric Nanomedicines for Comprehensive Regulation of Tumor Microenvironment

Hui-Xin Li; Rui-Ying Wu; Xin-Tong Mao; Xiao-Rui Zhou; Kai Hao; Hua-Yu Tian

doi:10.1007/s10118-026-3678-6

Your Location：

Home >

Browse articles >

Polymeric Nanomedicines for Comprehensive Regulation of Tumor Microenvironment

REVIEW | Updated：2026-06-11

- Polymeric Nanomedicines for Comprehensive Regulation of Tumor Microenvironment
- Polymeric Nanomedicines for Comprehensive Regulation of Tumor Microenvironment
- Chinese Journal of Polymer Science 2026年44卷第8期页码：2427-2452
- Affiliations：
  
  a.College of Chemistry and Chemical Engineering, Institute of Flexible Electronics (IFE, Future Technologies), Xiamen University, Xiamen 361005, China
  b.Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen University, Xiamen 361005, China
  c.Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
  d.School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
- Author bio：
  
  kaihao@xmu.edu.cn (K.H.)
  thy@xmu.edu.cn (H.Y.T.)
- Funds：
  
  This work was financially supported by the National Natural Science Foundation of China (Nos. 52433006, 52495010, 52495015 and 52503178), Fundamental Research Funds for the Central Universities (No. 20720230008), and Talent Cultivation Project Funds for the Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (HRTP-[2022] 52).;Kai Hao received his Ph.D. in Polymer Chemistry and Physics from the University of Science and Technology of China in 2021. Currently, he serves as an Assistant Professor at the Institute of Flexible Electronics (IFE, Future Technologies), Xiamen University. His research primarily focuses on the design of novel non-viral nucleic acid delivery vectors and their application in tumor immunotherapy.Hua-Yu Tian obtained his Ph.D. degree from the Changchun Institute of Applied Chemistry, Chinese Academy of Sciences in 2005. From 2006 to 2022, he conducted research at institutions including the Changchun Institute of Applied Chemistry, the Chinese Academy of Sciences, the Korea Advanced Institute of Science and Technology, Kyushu University, and the University of Utah. In 2022, he joined the College of Chemistry and Chemical Engineering at Xiamen University. His research topics include biomedical polymers, nanogene/drug carriers, biotherapy, nucleic acid vaccines, immunotherapy, and energy polymers.The authors declare no interest conflict.
- DOI：10.1007/s10118-026-3678-6
  中图分类号：
- 收稿：2026-02-28，
  
  录用：2026-03-18，
  
  网络首发：2026-06-10，
  
  纸质出版：2026-08-15
- Accepted：
Scan QR Code
Li, H. X.; Wu, R. Y.; Mao, X. T.; Zhou, X. R.; Hao, K.; Tian, H. Y. Polymeric nanomedicines for comprehensive regulation of tumor microenvironment. Chinese J. Polym. Sci. 2026, 44, 2427–2452

Hui-Xin Li, Rui-Ying Wu, Xin-Tong Mao, et al. Polymeric Nanomedicines for Comprehensive Regulation of Tumor Microenvironment[J]. Chinese Journal of Polymer Science, 2026, 44(8): 2427-2452.
Li, H. X.; Wu, R. Y.; Mao, X. T.; Zhou, X. R.; Hao, K.; Tian, H. Y. Polymeric nanomedicines for comprehensive regulation of tumor microenvironment. Chinese J. Polym. Sci. 2026, 44, 2427–2452 DOI： 10.1007/s10118-026-3678-6.

Hui-Xin Li, Rui-Ying Wu, Xin-Tong Mao, et al. Polymeric Nanomedicines for Comprehensive Regulation of Tumor Microenvironment[J]. Chinese Journal of Polymer Science, 2026, 44(8): 2427-2452. DOI： 10.1007/s10118-026-3678-6.

摘要

Polymeric nanomedicines provide versatile platforms for comprehensive tumor microenvironment (TME) regulation. By coordinating immune cell modulation and stromal remodeling

these systems dismantle biological barriers and transform “cold” tumors into a “hot” state to maximize synergistic anti-tumor immune activation.

Abstract

Cancer immunotherapy

which harnesses the host immune system to combat cancer

has advanced into preclinical and clinical trials. However

the tumor microenvironment (TME) usually promotes tumor angiogenesis and induces immune tolerance. Recently

polymeric nanomedicines with comprehensive regulation of the TME have attracted research interest. Compared with others

polymeric nanomedicines have outstanding characteristics

including facile preparation

improved tumor penetration

longer blood circulation

and better bioavailability. In particular

polymeric nanomedicines hold great potential for integrating combined treatments and imaging methods to concurrently modulate and trace the functional processes of multiple immune cells. This review summarizes the advances in polymeric nanomedicine-based strategies for TME regulation

including the regulation of TME stromal cells

the immune microenvironment matrix

and vasculature. Furthermore

the development of comprehensive polymeric nanomedicine-based theragnostic platforms integrated with imaging segments is briefly introduced.

关键词

Keywords

references

Yahya, E. B.; Alqadhi, A. M. Recent trends in cancer therapy: A review on the current state of gene delivery. Life Sci. 2021 , 269 , 119087..

Zhang, Y.; Zhang, W.; Wang, Y.; Zhu, J.; Zhou, M.; Peng, C.; He, Z.; Sun, J.; Li, Z.; Gui, S. Emerging nanotaxanes for cancer therapy. Biomaterials 2021 , 272 , 120790..

Aldonza, M. B. D.; Ku, J.; Hong, J.-Y.; Kim, D.; Yu, S. J.; Lee, M.-S.; Prayogo, S. T. M. C.; Kim, D.; Han, J.; Lee, S. K.; Im, S. G.; Ryu, H. S.; Kim, Y. Prior acquired resistance to paclitaxel relays diverse EGFR-targeted therapy persistence mechanisms. Sci. Adv. 2020 , 6 , eaav7416..

Chen, Q.; Sun, T.; Jiang, C. Recent advancements in nanomedicine for 'cold' tumor immunotherapy. Nanomicro Lett. 2021 , 13 , 92..

Jahanban-Esfahlan, R.; Seidi, K.; Monhemi, H.; Adli, A. D. F.; Minofar, B.; Zare, P.; Farajzadeh, D.; Farajnia, S.; Behzadi, R.; Abbasi, M. M.; Zarghami, N.; Javaheri, T. RGD delivery of truncated coagulase to tumor vasculature affords local thrombotic activity to induce infarction of tumors in mice. Sci. Rep. 2017 , 7 , 8126..

Baghban, R.; Roshangar, L.; Jahanban-Esfahlan, R.; Seidi, K.; Ebrahimi-Kalan, A.; Jaymand, M.; Kolahian, S.; Javaheri, T.; Zare, P. Tumor microenvironment complexity and therapeutic implications at a glance. Cell Commun. Signal. 2020 , 18 , 59..

Binnewies, M.; Roberts, E. W.; Kersten, K.; Chan, V.; Fearon, D. F.; Merad, M.; Coussens, L. M.; Gabrilovich, D. I.; Ostrand-Rosenberg, S.; Hedrick, C. C.; Vonderheide, R. H.; Pittet, M. J.; Jain, R. K.; Zou, W.; Howcroft, T. K.; Woodhouse, E. C.; Weinberg, R. A.; Krummel, M. F. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat. Med. 2018 , 24 , 541−550..

Li, X.; Yang, Y.; Huang, Q.; Deng, Y.; Guo, F.; Wang, G.; Liu, M. Crosstalk between the tumor microenvironment and cancer cells: A promising predictive biomarker for immune checkpoint inhibitors. Front. Cell Dev. Biol. 2021 , 9 , 738373..

Henke, E.; Nandigama, R.; Ergun, S. Extracellular matrix in the tumor microenvironment and its impact on cancer therapy. Front. Mol. Biosci. 2019 , 6 , 160..

Muntimadugu, E.; Kommineni, N.; Khan, W. Exploring the potential of nanotherapeutics in targeting tumor microenvironment for cancer therapy. Pharmacol. Res. 2017 , 126 , 109−122..

Ding, J.; Chen, J.; Gao, L.; Jiang, Z.; Zhang, Y.; Li, M.; Xiao, Q.; Lee, S. S.; Chen, X. Engineered nanomedicines with enhanced tumor penetration. Nano Today 2019 , 29 , 100800..

Min, Y.; Caster, J. M.; Eblan, M. J.; Wang, A. Z. Clinical translation of nanomedicine. Chem. Rev. 2015 , 115 , 11147−11190..

Oberoi, P.; Jabulowsky, R. A.; Bahr-Mahmud, H.; Wels, W. S. EGFR-targeted granzyme B expressed in NK cells enhances natural cytotoxicity and mediates specific killing of tumor cells. PLoS One 2013 , 8 , e61267..

Chi, L. H.; Cross, R. S. N.; Redvers, R. P.; Davis, M.; Hediyeh-Zadeh, S.; Mathivanan, S.; Samuel, M.; Lucas, E. C.; Mouchemore, K.; Gregory, P. A.; Johnstone, C. N.; Anderson, R. L. MicroRNA-21 is immunosuppressive and pro-metastatic via separate mechanisms. Oncogenesis 2022 , 11 , 38..

Bautista-Sanchez, D.; Arriaga-Canon, C.; Pedroza-Torres, A.; De La Rosa-Velazquez, I. A.; Gonzalez-Barrios, R.; Contreras-Espinosa, L.; Montiel-Manriquez, R.; Castro-Hernandez, C.; Fragoso-Ontiveros, V.; Alvarez-Gomez, R. M.; Herrera, L. A. The promising role of miR-21 as a cancer biomarker and its importance in RNA-based therapeutics. Mol. Ther. Nucleic Acids 2020 , 20 , 409−420..

Perez-Tomas, R.; Perez-Guillen, I. Lactate in the tumor microenvironment: An essential molecule in cancer progression and treatment. Cancers (Basel) 2020 , 12 , 3244..

Ozga, A. J.; Chow, M. T.; Luster, A. D. Chemokines and the immune response to cancer. Immunity 2021 , 54 , 859−874..

Domagala, J.; Lachota, M.; Klopotowska, M.; Graczyk-Jarzynka, A.; Domagala, A.; Zhylko, A.; Soroczynska, K.; Winiarska, M. The tumor microenvironment-a metabolic obstacle to NK cells' activity. Cancers (Basel) 2020 , 12 , 3542..

Wu, T.; Dai, Y. Tumor microenvironment and therapeutic response. Cancer Lett. 2017 , 387 , 61−68..

Vinogradov, S.; Warren, G.; Wei, X. Macrophages associated with tumors as potential targets and therapeutic intermediates. Nanomedicine (Lond.) 2014 , 9 , 695−707..

Pal, S.; Nandi, M.; Dey, D.; Chakraborty, B. C.; Shil, A.; Ghosh, S.; Banerjee, S.; Santra, A.; Ahammed, S. K. M.; Chowdhury, A.; Datta, S. Myeloid-derived suppressor cells induce regulatory T cells in chronically HBV infected patients with high levels of hepatitis B surface antigen and persist after antiviral therapy. Aliment. Pharmacol. Ther. 2019 , 49 , 1346−1359..

Lichtnekert, J.; Kawakami, T.; Parks, W. C.; Duffield, J. S. Changes in macrophage phenotype as the immune response evolves. Curr. Opin. Pharmacol. 2013 , 13 , 555−564..

Atri, C.; Guerfali, F. Z.; Laouini, D. Role of human macrophage polarization in inflammation during infectious diseases. Int. J. Mol. Sci. 2018 , 19 , 1801..

Ma, Z.; Yang, M.; Foda, M. F.; Zhang, K.; Li, S.; Liang, H.; Zhao, Y.; Han, H. Polarization of tumor-associated macrophages promoted by vitamin c-loaded liposomes for cancer immunotherapy. ACS Nano 2022 , 16 , 17389−17401..

Cao, M.; Yan, H.; Han, X.; Weng, L.; Wei, Q.; Sun, X.; Lu, W.; Wei, Q.; Ye, J.; Cai, X.; Hu, C.; Yin, X.; Cao, P. Ginseng-derived nanoparticles alter macrophage polarization to inhibit melanoma growth. J. Immunother. Cancer 2019 , 7 , 326..

Ye, C.; Yan, X.; Dai, X.; Chen, R.; Li, Q.; Xu, S.; Jiang, Q.; Yan, F.; Xu, S.; Zhao, C.-X.; Zhao, P.; Chen, D.; Ruan, J. Biocompatible snowman-like tumor-targeting dimer nanoparticles for improved delivery efficiency and enhanced anti-tumor therapy. Chem. Eng. J. 2023 , 474 , 145766..

Jiang, M.; Qi, Y.; Huang, W.; Lin, Y.; Li, B. Curcumin reprograms TAMs from a protumor phenotype towards an antitumor phenotype via inhibiting MAO-A/STAT6 pathway. Cells 2022 , 11 , 3473..

Zhang, Y.; Feng, Z.; Liu, J.; Li, H.; Su, Q.; Zhang, J.; Huang, P.; Wang, W.; Liu, J. Polarization of tumor-associated macrophages by TLR7/8 conjugated radiosensitive peptide hydrogel for overcoming tumor radioresistance. Bioact. Mater. 2022 , 16 , 359−371..

Figueiredo, P.; Lepland, A.; Scodeller, P.; Fontana, F.; Torrieri, G.; Tiboni, M.; Shahbazi, M. A.; Casettari, L.; Kostiainen,M. A.; Hirvonen, J.; Teesalu, T.; Santos, H. A. Peptide-guided resiquimod-loaded lignin nanoparticles convert tumor-associated macrophages from M2 to M1 phenotype for enhanced chemotherapy. Acta Biomater. 2021 , 133 , 231−243..

Wang, Y.; Li, G.; Su, J.; Liu, Y.; Zhang, X.; Zhang, G.; Wu, Z.; Li, J.; Wang, X.; Zhang, Y.; Bai, M.; Yao, Y.; Wang, R.; Shao, K. Tumor-associated macrophages nano-reprogrammers induce “gear effect” to empower glioblastoma immunotherapy. Small 2025 , 21 , 2406839..

Schnell, A.; Bod, L.; Madi, A.; Kuchroo, V. K. The yin and yang of co-inhibitory receptors:Toward anti-tumor immunity without autoimmunity. Cell Res. 2020 , 30 , 285−299..

Song, M.; Liu, T.; Shi, C.; Zhang, X.; Chen, X. Bioconjugated manganese dioxide nanoparticles enhance chemotherapy response by priming tumor-associated macrophages toward M1-like phenotype and attenuating tumor hypoxia. ACS Nano 2016 , 10 , 633−647..

Qiu, N.; Wang, G.; Wang, J.; Zhou, Q.; Guo, M.; Wang, Y.; Hu, X.; Zhou, H.; Bai, R.; You, M.; Zhang, Z.; Chen, C.; Liu, Y.; Shen, Y. Tumor-associated macrophage and tumor-cell dually transfecting polyplexes for efficient interleukin-12 cancer gene therapy. Adv. Mater. 2021 , 33 , e2006189..

Zhang, F.; Parayath, N. N.; Ene, C. I.; Stephan, S. B.; Koehne, A. L.; Coon, M. E.; Holland, E. C.; Stephan, M. T. Genetic programming of macrophages to perform anti-tumor functions using targeted mRNA nanocarriers. Nat. Commun. 2019 , 10 , 3974..

Li, Y.; Su, Z.; Zhao, W.; Zhang, X.; Momin, N.; Zhang, C.; Wittrup, K. D.; Dong, Y.; Irvine, D. J.; Weiss, R. Multifunctional oncolytic nanoparticles deliver self-replicating IL-12 RNA to eliminate established tumors and prime systemic immunity. Nat. Cancer 2020 , 1 , 882−893..

Hollen, M. K.; Stortz, J. A.; Darden, D.; Dirain, M. L.; Na cionales, D. C.; Hawkins, R. B.; Cox, M. C.; Lopez, M. C.; Rincon, J. C.; Ungaro, R.; Wang, Z.; Wu, Q.; Brumback, B.; Gauthier, M. L.; Kladde, M.; Leeuwenburgh, C.; Segal, M.; Bihorac, A.; Brakenridge, S.; Moore, F. A.; Baker, H. V.; Mohr, A. M.; Moldawer, L. L.; Efron, P. A. Myeloid-derived suppressor cell function and epigenetic expression evolves over time after surgical sepsis. Crit. Care 2019 , 23 , 355..

Veglia, F.; Sanseviero, E.; Gabrilovich, D. I. Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity. Nat. Rev. Immunol. 2021 , 21 , 485−498..

Lasser, S. A.; Ozbay Kurt, F. G.; Arkhypov, I.; Utikal, J.; Umansky, V. Myeloid-derived suppressor cells in cancer and cancer therapy. Nat. Rev. Clin. Oncol. 2024 , 21 , 147−164..

Law, A. M. K.; Valdes-Mora, F.; Gallego-Ortega, D. Myeloid-derived suppressor cells as a therapeutic target for cancer. Cells 2020 , 9 , 561..

Condamine, T.; Ramachandran, I.; Youn, J. I.; Gabrilovich, D. I. Regulation of tumor metastasis by myeloid-derived suppressor cells. Annu. Rev. Med. 2015 , 66 , 97−110..

Dai, X.; Ren, L.; Liu, M.; Cai, H.; Zhang, H.; Gong, Q.; Gu, Z.; Luo, K. Nanomedicines modulating myeloid-derived suppressor cells for improving cancer immunotherapy. Nano Today 2021 , 39 , 101163..

Zhang, Y.; Bush, X.; Yan, B.; Chen, J. A. Gemcitabine nanoparticles promote antitumor immunity against melanoma. Biomaterials 2019 , 189 , 48−59..

Liang, Y.; Wang, W.; Zhu, X.; Yu, M.; Zhou, C. Inhibition of myeloid-derived suppressive cell function with all-trans retinoic acid enhanced anti-PD-L1 efficacy in cervical cancer. Sci. Rep. 2022 , 12 , 9619..

Varikuti, S.; Singh, B.; Volpedo, G.; Ahirwar, D. K.; Jha, B. K.; Saljoughian, N.; Viana, A. G.; Verma, C.; Hamza, O.; Halsey, G.; Holcomb, E. A.; Maryala, R. J.; Oghumu, S.; Ganju, R. K.; Satoskar, A. R. Ibrutinib treatment inhibits breast cancer progression and metastasis by inducing conversion of myeloid-derived suppressor cells to dendritic cells. Br. J. Cancer 2020 , 122 , 1005−1013..

Qiu, Q.; Li, C.; Song, Y.; Shi, T.; Luo, X.; Zhang, H.; Hu, L.; Yan, X.; Zheng, H.; Liu, M.; Liu, M.; Liu, M.; Yang, S.; Liu, X.; Chen, G.; Deng, Y. Targeted delivery of ibrutinib to tumor-associated macrophages by sialic acid-stearic acid conjugate modified nanocomplexes for cancer immunotherapy. Acta Biomater. 2019 , 92 , 184−195..

Conniot, J.; Scomparin, A.; Peres, C.; Yeini, E.; Pozzi, S.; Matos, A. I.; Kleiner, R.; Moura, L. I. F.; Zupancic, E.; Viana, A. S.; Doron, H.; Gois, P. M. P.; Erez, N.; Jung, S.; Satchi-Fainaro, R.; Florindo, H. F. Immunization with mannosylated nanovaccines and inhibition of the immune-suppressing microenvironment sensitizes melanoma to immune checkpoint modulators. Nat. Nanotechnol. 2019 , 14 , 891−901..

Li, S.; Wang, Q.; Shen, Y.; Hassan, M.;Shen, J.; Jiang, W.; Su, Y.; Chen, J.; Bai, L.; Zhou, W.; Wang, Y. Pseudoneutrophil cytokine sponges disrupt myeloid expansion and tumor trafficking to improve cancer immunotherapy. Nano Lett. 2020 , 20 , 242−251..

Hammami, I.; Chen, J.; Murschel, F.; Bronte, V.; De Crescenzo, G.; Jolicoeur, M. Immunosuppressive activity enhances central carbon metabolism and bioenergetics in myeloid-derived suppressor cells. BMC Cell Biol. 2012 , 13 , 18..

Ledo, A. M.; Sasso, M. S.; Bronte, V.; Marigo, I.; Boyd, B. J.; Garcia-Fuentes, M.; Alonso,M. J. Co-delivery of RNAi and chemokine by polyar ginine nanocapsules enables the modulation of myeloid-derived suppressor cells. J. Control. Release 2019 , 295 , 60−73..

Wang, H.; Franco, F.; Ho, P. C. Metabolic regulation of Tregs in cancer: Opportunities for immunotherapy. Trends Cancer 2017 , 3 , 583−592..

Dejaco, C.; Duftner, C.; Grubeck-Loebenstein, B.; Schirmer, M. Imbalance of regulatory T cells in human autoimmune diseases. Immunology 2006 , 117 , 289−300..

Traxinger, B. R.; Richert-Spuhler, L. E.; Lund, J. M. Mucosal tissue regulatory T cells are integral in balancing immunity and tolerance at portals of antigen entry. Mucosal Immunol. 2022 , 15 , 398−407..

Huppert, L. A.; Green, M. D.; Kim, L.; Chow, C.; Leyfman, Y.; Daud, A. I.; Lee, J. C. Tissue-specific Tregs in cancer metastasis: Opportunities for precision immunotherapy. Cell. Mol. Immunol. 2022 , 19 , 33−45..

Tekguc, M.; Wing, J. B.; Osaki, M.; Long, J.; Sakaguchi, S. Treg-expressed CTLA-4 depletes CD80/CD86 by trogocytosis, releasing free PD-L1 on antigen-pres enting cells. Proc. Natl. Acad. Sci. U. S. A. 2021 , 118 , e2023739118..

Cheng, G.; Yu, A.; Malek, T. R. T-cell tolerance and the multi-functional role of IL-2R signaling in T-regulatory cells. Immunol. Rev. 2011 , 241 , 63−76..

Strauss, L.; Whiteside, T. L. Human circulating CD4+CD25high FOXP3+ regulatory T cells kill autologous CD8+ but not CD4+ responder cells by Fas-mediated apoptosis. J. Immunol. 2009 , 182 , 1469−1480..

Shalev, I.; Schmelzle, M.; Robson, S. C.; Levy, G. Making sense of regulatory T cell suppressive function. Semin. Immunol. 2011 , 23 , 282−292..

Gonzalez-Navajas, J. M.; Fan, D. D.; Yang, S.; Yang, F. M.; Lozano-Ruiz, B.; Shen, L.; Lee, J. The impact of Tregs on the anticancer immunity and the efficacy of immune checkpoint inhibitor therapies. Front. Immunol. 2021 , 12 , 625783..

Barati, M.; Mirzavi, F.; Nikpoor, A. R.; Sankian, M.; Namdar Ahmadabad, H.; Soleimani, A.; Mashreghi, M.; Tavakol Afshar, J.; Mohammadi, M.; Jaafari, M. R. Enhanced antitumor immun e response in melanoma tumor model by anti-PD-1 small interference RNA encapsulated in nanoliposomes. Cancer Gene Ther. 2022 , 29 , 814−824..

Vignali, D. A.; Collison, L. W.; Workman, C. J. How regulatory T cells work. Nat. Rev. Immunol. 2008 , 8 , 523−532..

Li, S. Y.; Liu, Y.; Xu, C. F.; Shen, S.; Sun, R.; Du, X. J.; Xia, J. X.; Zhu, Y. H.; Wang, J. Restoring anti-tumor functions of T cells via nanoparticle-mediated immune checkpoint modulation. J. Control. Release 2016 , 231 , 17−28..

Tanaka, A.; Sakaguchi, S. Targeting Treg cells in cancer immunotherapy. Eur. J. Immunol. 2019 , 49 , 1140−1146..

Ou, W.; Thapa, R. K.; Jiang, L.; Soe, Z. C.; Gautam, M.; Chang, J. H.; Jeong, J. H.; Ku, S. K.; Choi, H. G.; Yong, C. S.; Kim, J. O. Regulatory T cell-targeted hybrid nanoparticles combined with immuno-checkpoint blockage for cancer immunotherapy. J. Control. Release 2018 , 281 , 84−96..

Facciabene, A.; Motz, G. T.; Coukos, G. T-regulatory cells: Key players in tumor imm une escape and angiogenesis. Cancer Res. 2012 , 72 , 2162−2171..

Kim, D.; Wu, Y.; Li, Q.; Oh, Y. K. Nanoparticle-mediated lipid metabolic reprogramming of T cells in tumor microenvironments for immunometabolic therapy. Nanomicro Lett. 2021 , 13 , 31..

Zhang, N.; Liu, S.; Shi, S.; Chen, Y.; Xu, F.; Wei, X.; Xu, Y. Solubilization and delivery of ursolic-acid for modulating tumor microenvironment and regulatory T cell activities in cancer immunotherapy. J. Control. Release 2020 , 320 , 168−178..

Wang, M.; Yan, D.; Wang, M.; Wu, Q.; Song, R.; Huang, Y.; Rao, J.; Wang, D.; Zhou, F.; Tang, B. Z. A versatile 980 nm absorbing aggregation-induced emission luminogen for NIR-II imaging-guided synergistic photo-immunotherapy against advanced pancreatic cancer. Adv. Funct. Mater. 2022 , 32 , 2205371..

He, S.; Li, J.; Cheng, P.; Zeng, Z.; Zhang, C.; Duan, H.; Pu, K. Charge-reversal polymer nano-modulators for photodynamic immunotherapy of cancer. Angew. Chem. Int. Ed. 2021 , 60 , 19355−19363..

Erdogan, B.; Webb, D. J. Cancer-associated fibroblasts modulate growth factor signalingand extracellular matrix remodeling to regulate tumor metastasis. Biochem. Soc. Trans. 2017 , 45 , 229−236..

Chen, Y.; Hu, M.; Wang, S.; Wang, Q.; Lu, H.; Wang, F.; Wang, L.; Peng, D.; Chen, W. Nano-delivery of salvianolic acid B induces the quiescence of tumor-associated fibroblasts via interfering with TGF-beta1/Smad signaling to facilitate chemo- and immunotherapy in desmoplastic tumor. Int. J. Pharm. 2022 , 623 , 121953..

Cun, X.; Chen, J.; Li, M.; He, X.; Tang, X.; Guo, R.; Deng, M.; Li, M.; Zhang, Z.; He, Q. Tumor-associated fibroblast-targeted regulation and deep tumor delivery of chemotherapeutic drugs with a multifunctional size-switchable nanoparticle. ACS Appl. Mater. Interfaces 2019 , 11 , 39545−39559..

Hu, K.; Miao, L.; Goodwin, T. J.; Li, J.; Liu, Q.; Huang, L. Quercetin remodels the tumor microenvironment to improve the permeation, retention, and antitumor effects of nanoparticles. ACS Nano 2017 , 11 , 4916−4925..

Munir, M. U. Nanomedicine penetration to tumor: Challenges, and advanced strategies to tackle this issue. Cancers (Basel) 2022 , 14 , 2904..

Khawar, I. A.; Kim, J. H.; Kuh, H. J. Improving drug delivery to solid tumors: Priming the tumor microenvironment. J. Control. Release 2015 , 201 , 78−89..

Li, L.; Zhou, S.; Lv, N.; Zhen, Z.; Liu, T.; Gao, S.; Xie, J.; Ma, Q. Photosensitizer-encapsulated ferritins mediate photodynamic therapy against cancer-associated fibroblasts and improve tumor accumulation of nanoparticles. Mol. Pharm. 2018 , 15 , 3595−3599..

Han, H.; Hou, Y.; Chen, X.; Zhang, P.; Kang, M.; Jin, Q.; Ji, J.; Gao, M. Metformin-induced stromal depletion to enhance the penetration of gemcitabine-loaded magnetic nanoparticles for pancreatic cancer targeted therapy. J. Am. Chem. Soc. 2020 , 142 , 4944−4954..

Wang, H.; Han, X.; Dong, Z.; Xu, J.; Wang, J.; Liu, Z. Hyaluronidase with pH-responsive dextran modification as an adjuvant nanomedicine for enhanced photodynamic-immunotherapy of cancer. Adv. Funct. Mater. 2019 , 29 , 1902440..

Hsieh, P. H.; Huang, W. Y.; Wang, H. C.; Kuan, C. H.; Shiue, T. Y.; Chen, Y.; Wang, T. W. Dual-re sponsive polypeptide nanoparticles attenuate tumor-associated stromal desmoplasia and anticancer through programmable dissociation. Biomaterials 2022 , 284 , 121469..

Shang, T.; Yu, X.; Han, S.; Yang, B. Nanomedicine-based tumor photothermal therapy synergized immunotherapy. Biomater. Sci. 2020 , 8 , 5241−5259..

Tan, T.; Hu, H.; Wang, H.; Li, J.; Wang, Z.; Wang, J.; Wang, S.; Zhang, Z.; Li, Y. Bioinspired lipoproteins-mediated photothermia remodels tumor stroma to improve cancer cell accessibility of second nanoparticles. Nat. Commun. 2019 , 10 , 3322..

Fang, T.; Zhang, J.; Zuo, T.; Wu, G.; Xu, Y.; Yang, Y.; Yang, J.; Shen, Q. Chemo-photothermal combination cancer therapy with ROS scavenging, extracellular matrix depletion, and tumor immune activation by telmisartan and diselenide-paclitaxel prodrug loaded nanoparticles. ACS Appl. Mater. Interfaces 2020 , 12 , 31292−31308..

Liu, Y.; Huo, Y.; Yao, L.; Xu, Y.; Meng, F.; Li, H.; Sun, K.; Zhou, G.; Kohane, D. S.; Tao, K. Transcytosis of nanomedicine for tumor penetration. Nano Lett. 2019 , 19 , 8010−8020..

Yan, Y.; Chen, B.; Wang, Z.; Yin, Q.; Wang, Y.; Wan, F.; Mo, Y.; Xu, B.; Zhang, Q.; Wang, S.; Wang, Y. Sequential modulations of tumor vasculature and stromal barriers augment the active targeting efficacy of antibody-modified nanophoto sensitizer in desmoplastic ovarian carcinoma. Adv. Sci. (Weinh) 2021 , 8 , 2002253..

Nagy, J. A.; Chang, S. H.; Shih, S. C.; Dvorak, A. M.; Dvorak, H. F. Heterogeneity of the tumor vasculature. Semin. Thromb. Hemost. 2010 , 36 , 321−331..

Barua, S.; Mitragotri, S. Challenges associated with penetration of nanoparticles across cell and tissue barriers: A review of current status and future prospects. Nano Today 2014 , 9 , 223−243..

Luo, J.; Zhong, X.; Peng, Y.; Hao, C.; Liang, X.; Yang, Y.; Shi, X.; Chen, X.; Yi, X.; Li, X.; Wu, J.; Li, J.; Xiao, Q.; Wu, C.; Lu, R.; Pan, Y.; Wang, X.; Fan, J. B.; Wang, Y.; Wang, Y. Self-anti-angiogenesis nanoparticles enhance anti-metastatic-tumor efficacy of chemotherapeutics. Bioact. Mater. 2022 , 13 , 179−190..

Tang, Y.; Jia, C.; Wang, Y.; Wan, W.; Li, H.; Huang, G.; Zhang, X. Lactate consumption via cascaded enzymes combined VE GF siRNA for synergistic anti-proliferation and anti-angiogenesis therapy of tumors. Adv. Healthc. Mater. 2021 , 10 , e2100799..

Sun, C.; Gao, S.; Tan, Y.; Zhang, Z.; Xu, H. Side-chain selenium-grafted polymers combining antiangiogenesis treatment with photodynamic therapy and chemotherapy. ACS Biomater. Sci. Eng. 2021 , 7 , 3201−3208..

Li, S.; Zhang, Y.; Ho, S. H.; Li, B.; Wang, M.; Deng, X.; Yang, N.; Liu, G.; Lu, Z.; Xu, J.; Shi, Q.; Han, J. Y.; Zhang, L.; Wu, Y.; Zhao, Y.; Nie, G. Combination of tumour-infarction therapy and chemotherapy via the co-delivery of doxorubicin and thrombin encapsulated in tumour-targeted nanoparticles. Nat. Biomed. Eng. 2020 , 4 , 732−742..

Bule, P.; Aguiar, S. I.; Aires-Da-Silva, F.; Dias, J. N. R. Chemokine-directed tumor microenvironment modulation in cancer immunotherapy. Int. J. Mol. Sci. 2021 , 22 , 9804..

Elsabahy, M.; Wooley, K. L. Cytokines as biomarkers of nanoparticle immunotoxicity. Chem. Soc. Rev. 2013 , 42 , 5552−5576..

[Wang, Y.; Tiruthani, K.; Li, S.; Hu, M.; Zhong, G.; Tang, Y.; Roy, S.; Zhang, L.; Tan, J.; Liao, C.; Liu, R. mRNA delivery of a bispecific single-domain antibody to polarize tumor-associated macrophages and synergize immunotherapy against liver malignancies. Adv. Mater . 2021 , 33 , e2007603..

Catalan, D.; Mansilla, M. A.; Ferrier, A.; Soto, L.; Oleinika, K.; Aguillon, J. C.; Aravena, O. Immunosuppressive mechanisms of regulatory B cells. Front. Immunol. 2021 , 12 , 611795..

Gao, S. H.; Liu, S. Z.; Wang, G. Z.; Zhou, G. B. CXCL13 in cancer and other diseases: Biological functions, clinical significance, and therapeutic opportunities. Life (Basel) 2021 , 11 , 1282..

Shen, L.; Li, J.; Liu, Q.; Das, M.; Song, W.; Zhang, X.; Tiruthani, K.; Dorosheva, O.; Hu, H.; Lai, S. K.; Liu, R.; Huang, L. Nano-trapping CXCL13 reduces regulatory B cells in tumor microenvironment and inhibits tumor growth. J. Control. Release 2022 , 343 , 303−313..

Ren, X.; Cheng, Z.; He, J.; Yao, X.; Liu, Y.; Cai, K.; Li, M.; Hu, Y.; Luo, Z. Inhibition of glycolysis-driven immunosuppression with a nano-assembly enhances response to immune checkpoint blocka de therapy in triple negative breast cancer. Nat. Commun. 2023 , 14 , 7021..

Chen, J.; Bu, C.; Lu, Y.; Peng, X.; Yu, J.; Ding, X.; Yuan, P.; Hong, S. Bioresponsive nanoreactor initiates cascade reactions for tumor vascular normalization and lactate depletion to augment immunotherapy. Biomaterials 2025 , 317 , 123100..

Guo, X.; Chen, X.; Ding, J.; Zhang, F.; Chen, S.; Hu, X.; Fang, S.; Shen, L.; Lu, C.; Zhao, Z.; Tu, J.; Shu, G.; Chen, M.; Ji, J. Acidic/hypoxia dual-alleviated nanoregulators for enhanced treatment of tumor chemo-immunotherapy. Asian J. Pharm. Sci. 2024 , 19 , 100905..

Hamouda, A. E. I.; Filtjens, J.; Brabants, E.; Kancheva, D.; Debraekeleer, A.; Brughmans, J.; Jacobs, L.; Bardet, P. M. R.; Knetemann, E.; Lefesvre, P.; Allonsius, L.; Gontsarik, M.; Varela, I.; Crabbé, M.; Clappaert, E. J.; Cappellesso, F.; Caro, A. A.; Gordún Peiró, A.; Fredericq, L.; Hadadi, E.; Estapé Senti, M.; Schiffelers, R.; van Grunsven, L. A.; Aboubakar Nana, F.; De Geest, B. G.; Deschoemaeker, S.; De Koker, S.; Lambolez, F.; Laoui, D. Intratumoral delivery of lipid nanoparticle-formulated mRNA encoding IL-21, IL-7, and 4-1BBL induces systemic anti-tumor immunity. Nat. Commun. 2024 , 15 , 10653..

Portale, F.; Carriero, R.; Iovino, M.; Kunderfranco, P.; Pandini, M.; Marelli, G.; Morina, N.; Lazzeri, M.; Casale, P.; Colombo, P.; De Simone, G.; Camisaschi, C.; Lugli, E.; Basso, G.; Cibella, J.; Marchini, S.; Bordi, M.; Meregalli, G.; Garbin, A.; Dambra, M.; Magrini, E.; Rackwitz, W.; Cecconi, F.; Corbelli, A.; Fiordaliso, F.; Eitler, J.; Tonn, T.; Di Mitri, D. C/EBPβ-dependent autophagy inhibition hinders NK cell function in cancer. Nat. Commun. 2024 , 15 , 10343..

Cao, C.; Xu, M.; Wei, Y.; Peng, T.; Lin, S.; Liu, X.; Xu, Y.; Chu, T.; Liu, S.; Wu, P.; Hu, B.; Ding, W.; Li, L.; Ma, D.; Wu, P. CXCR4 orchestrates the TOX-programmed exhausted phenotype of CD8+ T cells via JAK2/STAT3 pathway. Cell Genomics 2024 , 4 , 100659..

Zhou, D.; Shao, L.; Spitz, D. R. Reactive oxygen species in normal and tumor stem cells. Adv. Cancer Res. 2014 , 122 , 1−67..

Schiliro, C.; Firestein, B. L. Mechanisms of metabolic reprogramming in cancer cells supporting enhanced growth and proliferation. Cells 2021 , 10 , 1056..

Arlauckas, S. P.; Garren, S. B.; Garris, C. S.; Kohler, R. H.; Oh, J.; Pittet, M. J.; Weissleder, R. ARG1 expression defines immunosuppressive subsets of tumor- associated macrophages. Theranostics 2018 , 8 , 5842−5854..

Tian, L. R.; Lin, M. Z.; Zhong, H. H.; Cai, Y. J.; Li, B.; Xiao, Z. C.; Shuai, X. T. Nanodrug regulates lactic acid metabolism to reprogram the immunosuppressive tumor microenvironment for enhanced cancer immunotherapy. Biomater. Sci. 2022 , 10 , 3892−3900..

Choi, H.; Yeo, M.; Kang, Y.; Kim, H. J.; Park, S. G.; Jang, E.; Park, S. H.; Kim, E.; Kang, S. Lactate oxidase/catalase-displaying nanoparticles efficiently consume lactate in the tumor microenvironment to effectively suppress tumor growth. J. Nanobiotechnol. 2023 , 21 , 5..

Wei, D.; Cheng, X.; Du, C.; Wang, Y.; Sun, J.; Li, C.; Wu, J.; Tian, X.; Zhao, Y.; Nie, G.; Yang, Y. Stroma-targeted nanoparticles that remodel stromal alignment to enhance drug delivery and improve the antitumor efficacy of nab-paclitaxel in pancreatic ductal adenocarcinoma models. Nano Today 2022 , 45 , 101533..

Tan, H. Y.; Wang, N.; Li, S.; Hong, M.; Wang, X.; Feng, Y. The reactive oxygen species in macrophage polarization: Reflecting its dual role in progression and treatment of human diseases. Oxid. Med. Cell. Longev. 2016 , 2016 , 2795090..

Sang, Y.; Deng, Q.; Cao, F.; Liu, Z.; You, Y.; Liu, H.; Ren, J.; Qu, X. Remodeling macrophages by an iron nanotrap for tumor growth suppression. ACS Nano 2021 , 15 , 19298−19309..

Liu, Q.; Shi, L.; Liao, Y.; Cao, X.; Liu, X.; Yu, Y.; Wang, Z.; Lu, X.; Wang, J. Ultrathin-FeOOH-coated MnO 2 sonosensitizers with boosted reactive oxygen species yield and remodeled tumor microenvironment for efficient cancer therapy. Adv. Sci. 2022 , 9 , 2200005..

Dong, Z.; Wang, C.; Gong, Y.; Zhang, Y.; Fan, Q.; Hao, Y.; Li, Q.; Wu, Y.; Zhong, X.; Yang, K.; Feng, L.; Liu, Z. Chemical modulation of glucose metabolism with a fluorinated CaCO 3 nanoregulator can potentiate radiotherapy by programming antitumor immunity. ACS Nano 2022 , 16 , 13884−13899..

Wu, J.; Chen, J.; Feng, Y.; Zhang, S.; Lin, L.; Guo, Z.; Sun, P.; Xu, C.; Tian, H.; Chen, X. An immune cocktail therapy to realize multiple boosting of the cancer-immunity cycle by combination of drug/gene delivery nanoparticles. Sci. Adv. 2020 , 6 , eabc7828..

Wu, J .; Guo, Z.; Ni, W.; Feng, Y.; Guo, X.; Meng, M.; Yuan, Y.; Lin, L.; Chen, J.; Tian, H.; Chen, X. Novel cocktail therapy based on a nanocarrier with an efficient transcytosis property reverses the dynamically deteriorating tumor microenvironment for enhanced immunotherapy. Nano Lett. 2022 , 22 , 7220−7229..

Feng, Y.; Wu, J.; Chen, J.; Lin, L.; Zhang, S.; Yang, Z.; Sun, P.; Li, Y.; Tian, H.; Chen, X. Targeting dual gene delivery nanoparticles overcomes immune checkpoint blockade induced adaptive resistance and regulates tumor microenvironment for improved tumor immunotherapy. Nano Today 2021 , 38 , 101194..

Fang, H.; Chen, J.; Lin, L.; Liu, F.; Tian, H.; Chen, X. A strategy of killing three birds with one stone for cancer therapy through regulating the tumor microenvironment by H2O2-responsive gene delivery system. ACS Appl. Mater. Interfaces 2019 , 11 , 47785−47797..

Liu, S.; Wu, J.; Feng, Y.; Guo, X.; Li, T.; Meng, M.; Chen, J.; Chen, D.; Tian, H. CD47KO/CRT dual-bioengineered cell membrane-coated nanovaccine combined with anti-PD-L1 antibody for boosting tumor immunotherapy. Bioact. Mater. 2023 , 22 , 211−224..

Zhang, S.; Zhang, Y.; Feng, Y.; Wu, J.; Hu, Y.; Lin, L.; Xu, C.; C hen, J.; Tang, Z.; Tian, H.; Chen, X. Biomineralized two-enzyme nanoparticles regulate tumor glycometabolism inducing tumor cell pyroptosis and robust antitumor immunotherapy. Adv. Mater. 2022 , 34 , e2206851..

Huang, J.; Zhuang, C.; Chen, J.; Chen, X.; Li, X.; Zhang, T.; Wang, B.; Feng, Q.; Zheng, X.; Gong, M.; Gong, Q.; Xiao, K.; Luo, K.; Li, W. Targeted drug/gene/photodynamic therapy via a stimuli-responsive dendritic-polymer-based nanococktail for treatment of EGFR-TKI-resistant non-small-cell lung cancer. Adv. Mater. 2022 , 34 , e2201516..

Yu, C.; Liang, C.; Tao, H.; Du, Y.; Wu, D.; Dong, Z.; Jin, Q.; Chen, G.; Xu, J.; Xiao, Z.; Chen, Q.; Wang, C.; Chen, J.; Liu, Z. Localized cocktail chemoimmunotherapy after in situ gelation to trigger robust systemic antitumor immune responses. Sci. Adv. 2020 , 6 , eaaz4204..

Wang, Z.; Wang, Q.; Cao, H.; Wang, Z.; Wang, D.; Liu, J.; Gao, T.; Ren, C.; Liu, J. Mitochondrial localized in situ self-assembly reprogramming tumor immune and metabolic microenvironment for enhanced cancer therapy. Adv. Mater. 2024 , 36 , 2311043..

Luo, H.; Lv, J.; Wen, P.; Zhang, S.; Ma, W.; Yang, Z. Supramolecular pol yrotaxane-based nano-theranostics enable cancer-cell stiffening for enhanced T-cell-mediated anticancer immunotherapy. Nat. Commun. 2025 , 16 , 2331..

An, J. X.; Qin, Y. T.; Tang, Y.; He, J. L.; Zhang, C.; Rao, Z. Y.; Xie, T. Q.; Zhang, X. Z. Polymerization of L-arginine into nanomicelles for immunometabolic engineering of adoptive macrophages in solid tumor therapy. Angew. Chem. Int. Ed. 2025 , 64 , e202507476..

Ying, W.; Zheng, C.; Gong, C.; Yuan, J.; Xu, G.; Zhou, J.; Fan, C.; Zhang, Y.; Luo, J.; Dan, R.; Huang, Y.; Li, X.; Chen, W.; Zhang, K.; Xing, M.; Wang, L.; Wang, H.; Yang, S.; Luo, Q. Nanorobots hold PD-L1 and break membrane of colorectal cancer cells for immunotherapy. Nat. Nanotechnol. 2025 , 21 , 156−167..

Gulzar, A.; Xu, J.; Wang, C.; He, F.; Yang, D.; Gai, S.; Yang, P.; Lin, J.; Jin, D.; Xing, B. Tumour microenvironment responsive nanoconstructs for cancer theranostic. Nano Today 2019 , 26 , 16−56..

Cho, H.; Kwon, H. Y.; Sharma, A.; Lee, S. H.; Liu, X.; Miyamoto, N.; Kim, J. J.; Im, S. H.; Kang, N. Y.; Chang, Y. T. Visualizing inflammation with an M1 macrophage selective probe via GLUT1 as the gating target. Nat. Commun. 2022 , 13 , 5974..

Yang, X.; Zhao, M.; Wu, Z.; Chen, C.; Zhang, Y.; Wang, L.; Guo, Q.; Wang, Q.; Liang, S.; Hu, S.; Duan, Y.; Sun, Y. Nano-ultrasonic contrast agent for chemoimmunotherapy of breast cancer by immune metabolism reprogramming and tumor autophagy. ACS Nano 2022 , 16 , 3417−3431..

Hong, G.; Antaris, A. L.; Dai, H. Near-infrared fluorophores for biomedical imaging. Nat. Biomed. Eng. 2017 , 1 , 0010..

Sun, Y.; Ding, F.; Zhou, Z.; Li, C.; Pu, M.; Xu, Y.; Zhan, Y.; Lu, X.; Li, H.; Yang, G.; Sun, Y.; Stang, P. J. Rhomboidal Pt (II) metallacycle-based NIR-II theranostic nanoprobe for tumor diagnosis and image-guided therapy. Proc. Natl. Acad. Sci. U. S. A. 2019 , 116 , 1968−1973..

Wang, Z.; Ding, T.; Wang, L.; Wang, S.; Zhou, M.; Zhang, J.; Cai, K. Exo/endogenous factors co-activatable nanodevice for spatiotemporally controlled miRNA imaging and guided tumor ablation. Nano Res. 2021 , 15 , 845−857..

He, S.; Li, J.; Lyu, Y.; Huang, J.; Pu, K. Near-infrared fluorescent macromolecular reporte rs for real-time imaging and urinalysis of cancer immunotherapy. J. Am. Chem. Soc. 2020 , 142 , 7075−7082..

He, S.; Cheng, P.; Pu, K. Activatable near-infrared probes for the detection of specific populations of tumour-infiltrating leukocytes in vivo and in urine. Nat. Biomed. Eng. 2023 , 7 , 281−297..

Belikov, A. V.; Schraven, B.; Simeoni, L. T cells and reactive oxygen species. J. Biomed. Sci. 2015 , 22 , 85..

Shi, C.; Zhang, Q.; Yao, Y.; Zeng, F.; Du, C.; Nijiati, S.; Wen, X.; Zhang, X.; Yang, H.; Chen, H.; Guo, Z.; Zhang, X.; Gao, J.; Guo, W.; Chen, X.; Zhou, Z. Targeting the activity of T cells by membrane surface redox regulation for cancer theranostics. Nat. Nanotechnol. 2022 , 18 , 86−97..

浏览量

127

Downloads

CSCD

文章被引用时，请邮件提醒。

Submit

工具集

关联资源

A Polymer Cathode Interlayer Based on B←N Unit for Suppressed Dark Current in Organic Photodetectors

The Effect of Polymerization of Ionic Liquid [C4Vim]Br on Phase Behavior and Partitioning of L-tryptophan: Experimental and Molecular Dynamics Study

A Simple Method for Evaluating Periodic Structures Based on Atomic Force Microscopy Images

Designable Optical Polyesters via Alternating Copolymerization of Benzaldehyde-derived Cyclic Carbonates and Phthalic Anhydride

Soft-segment-engineered Self-healing Polyurethane for High-performance Electrorheological Elastomers and Capacitive Sensors