The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Binary Cooperative Prodrug Nanoparticles Improve Immunotherapy by Synergistically Modulating Immune Tumor Microenvironment
Abstract
Checkpoint blockade immunotherapy is promising for clinical treatment of various malignant tumors. However, checkpoint blockade immunotherapy suffers from a low response rate due to insufficient tumor immunogenicity and the immunosuppressive tumor microenvironment (ITM). In this study, a tumor‐microenvironment‐activatable binary cooperative prodrug nanoparticle (BCPN) is rationally designed to improve immunotherapy by synergistically modulating the immune tumor microenvironment. BCPN is purely constructed from a tumor acidity and reduction dual‐responsive oxaliplatin (OXA) prodrug for triggering immunogenic cell death (ICD) and eliciting antitumor immunity, and a reduction‐activatable homodimer of NLG919 for inactivating indoleamine 2,3‐dioxygenase 1, which is a key regulator for ITM. Upon tumor‐acidity‐triggered cleavage of the poly(ethylene glycol) shell, PN shows negative to positive charge switch for enhanced tumor accumulation and deep penetration. OXA and NLG919 are then activated in the tumor cells via glutathione‐mediated reduction. It is demonstrate that activated OXA promotes intratumoral accumulation of cytotoxic T lymphocytes by triggering ICD of cancer cells. Meanwhile, NLG919 downregulates IDO‐1‐mediated immunosuppression and suppresses regulatory T cells. Most importantly, PN shows much higher efficiency than free OXA or the combination of free OXA and NLG919 to regress tumor growth and prevent metastasis of mouse models of both breast and colorectal cancer.
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Cites
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Cited by
Zhou, W., Zhou, Y., Chen, X., Ning, T., Chen, H., Guo, Q., Zhang, Y., Liu, P., Zhang, Y., Li, C., et al. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2020.120546 · Cited by 425
Ding, B., Zheng, P., Jiang, F., Zhao, Y., Wang, M., Chang, M., Ma, P., & Lin, J. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202005111 · Cited by 341
Stimuli-Responsive Polymer-Based Nanosystems for Cancer Theranostics
Wei, D., Sun, Y., Zhu, H., & Fu, Q. (2023) · ACS Nano · doi:10.1021/acsnano.3c06019 · Cited by 303
Engineering nanomedicines through boosting immunogenic cell death for improved cancer immunotherapy
Gao, J., Wang, W.-Q., Pei, Q., Lord, M. S., & Yu, H.-J. (2020) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-0400-z · Cited by 203
Self-citationChen, H., Liu, L., Ma, A., Yin, T., Chen, Z., Liang, R., Qiu, Y., Zheng, M., & Cai, L. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2020.120639 · Cited by 144
Metadata
- Authors
- Feng, B., Zhou, F., Hou, B., Wang, D., Wang, T., Fu, Y., Ma, Y., Yu, H., & Li, Y.
- Venue
- Advanced Materials
- Publisher
- Wiley
- Published
- 2018-07-31
- Volume
- 30
- Issue
- 38
- Pages
- e1803001-e1803001
- ISSN
- 0935-9648 (ISSN-L)
- 1521-4095
- OpenAlex
- W2886471216
- Cited by
- 451
- References
- 6
- FWCI
- 16.55
- Type
- journal article
- Language
- en
- Open access
- closed
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