Tumor Microenvironment‐Induced Drug Depository for Persistent Antitumor Chemotherapy and Immune Activation

Herein, a drug‐loading nanosystem that can in situ form drug depository for persistent antitumor chemotherapy and immune regulation is designed and built. The system (DOX@MIL‐LOX@AL) is fabricated by packaging alginate on the surface of Doxorubicin (DOX) and lactate oxidase (LOX) loaded MIL‐101(Fe)‐...

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Bibliographic Details
Published in:Small (Weinheim an der Bergstrasse, Germany) Germany), 2024-04, Vol.20 (15), p.e2307736-n/a
Main Authors: Gao, Fan, Xue, Chun, Dong, Jianhui, Lu, Xinxin, Yang, Nan, Ou, Changjin, Mou, Xiaozhou, Zhang, Yi‐Zhou, Dong, Xiaochen
Format: Article
Language:English
Subjects:
Alginates
antitumor
Calcium ions
Chemotherapy
Doxorubicin
drug depository
Hydrogen peroxide
immune regulation
Iron
Lactic acid
Liquid oxygen
Nanoparticles
Oxidation
tumor microenvironment
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Summary:Herein, a drug‐loading nanosystem that can in situ form drug depository for persistent antitumor chemotherapy and immune regulation is designed and built. The system (DOX@MIL‐LOX@AL) is fabricated by packaging alginate on the surface of Doxorubicin (DOX) and lactate oxidase (LOX) loaded MIL‐101(Fe)‐NH2 nanoparticle, which can easily aggregate in the tumor microenvironment through the cross‐linking with intratumoral Ca2+. Benefiting from the tumor retention ability, the fast‐formed drug depository will continuously release DOX and Fe ions through the ATP‐triggered slow degradation, thus realizing persistent antitumor chemotherapy and immune regulation. Meanwhile, LOX in the non‐aggregated nanoparticles is able to convert the lactic acid to H2O2, which will be subsequently decomposed into ·OH by Fe ions to further enhance the DOX‐induced immunogenic death effect of tumor cells. Together, with the effective consumption of immunosuppressive lactic acid, long‐term chemotherapy, and oxidation therapy, DOX@MIL‐LOX@AL can execute high‐performance antitumor chemotherapy and immune activation with only one subcutaneous administration. An intratumoral Ca2+‐responsive aggregation nanosystem DOX@MIL‐LOX@AL is constructed to fast form a drug depository in tumors. With the consumption of lactic acid, the persistent release of DOX and Fe3+ (Fenton catalyst) for more than 7 days in tumors, this nanosystem exhibits effective synergistic chemotherapy and immunotherapy for tumors with only single‐dose.
ISSN:1613-6810
1613-6829
DOI:10.1002/smll.202307736