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Transformable Honeycomb‐Like Nanoassemblies of Carbon Dots for Regulated Multisite Delivery and Enhanced Antitumor Chemoimmunotherapy
Author(s) -
Hou Lin,
Chen Dandan,
Wang Ruiting,
Wang Ruibing,
Zhang Huijuan,
Zhang Zhenzhong,
Nie Zhihong,
Lu Siyu
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202014397
Subject(s) - chemoimmunotherapy , desmoplasia , cancer research , tumor microenvironment , drug delivery , stroma , nanomedicine , doxorubicin , immunotherapy , in vivo , immune system , materials science , nanotechnology , medicine , immunology , chemotherapy , tumor cells , nanoparticle , biology , immunohistochemistry , surgery , microbiology and biotechnology
Tumor fibrotic stroma forms complex barriers for therapeutic nanomedicine. Although nanoparticle vehicles are promising in overcoming biological barriers for drug delivery, fibrosis causes hypoxia, immunosuppression and limited immunocytes infiltration, and thus reduces antitumor efficacy of nanosystems. Herein, we report the development of cancer‐associated fibroblasts (CAFs) responsive honeycomb‐like nanoassemblies of carbon dots (CDs) to spatially program the delivery of multiple therapeutics for enhanced antitumor chemoimmunotherapy. Doxorubicin (DOX) and immunotherapeutic enhancer (Fe ions) are immobilized on the surface of CDs, whereas tumor microenvironment modifier (losartan, LOS) is encapsulated within the mesopores. The drugs‐loaded nanoassemblies disassociate into individual CDs to release LOS to mitigate stroma and hypoxia in response to CAFs. The individual CDs carrying DOX and Fe ion efficiently penetrate deep into tumor to trigger intensified immune responses. Our in vitro and in vivo studies show that the nanoassemblies exhibit effective T cells infiltration, tumor growth inhibition and lung metastasis prevention, thereby providing a therapeutic platform for desmoplasia solid tumor.