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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\u2010associated fibroblasts (CAFs) responsive honeycomb\u2010like 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\u2010loaded 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.<\/jats:p>","DOI":"10.1002\/anie.202014397","type":"journal-article","created":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T13:09:30Z","timestamp":1607692170000},"page":"6581-6592","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":137,"title":["Transformable Honeycomb\u2010Like Nanoassemblies of Carbon Dots for Regulated Multisite Delivery and Enhanced Antitumor Chemoimmunotherapy"],"prefix":"10.1002","volume":"60","author":[{"given":"Lin","family":"Hou","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases Collaborative Innovation Center of New Drug Research and Safety Evaluation Zhengzhou University 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