Bioorthogonal in situ assembly of nanomedicines as drug depots for extracellular drug delivery

Ziyang Cao, Dongdong Li, Liang Zhao, Mengting Liu, Pengyue Ma, Yingli Luo and Xianzhu Yang ()
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Ziyang Cao: South China University of Technology
Dongdong Li: South China University of Technology, Guangzhou International Campus
Liang Zhao: South China University of Technology, Guangzhou International Campus
Mengting Liu: South China University of Technology, Guangzhou International Campus
Pengyue Ma: South China University of Technology
Yingli Luo: South China University of Technology
Xianzhu Yang: South China University of Technology

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Developing precise nanomedicines to improve the transport of anticancer drugs into tumor tissue and to the final action site remains a critical challenge. Here, we present a bioorthogonal in situ assembly strategy for prolonged retention of nanomedicines within tumor areas to act as drug depots. After extravasating into the tumor site, the slightly acidic microenvironment induces the exposure of cysteine on the nanoparticle surface, which subsequently undergoes a bioorthogonal reaction with the 2-cyanobenzothiazole group of another neighboring nanoparticle, enabling the formation of micro-sized drug depots to enhance drug retention and enrichment. This in situ nanoparticle assembly strategy remarkably improves the antimetastatic efficacy of extracellular-targeted drug batimastat, and also leads to the simultaneous enhanced retention and sustained release of multiple agents for combined cocktail chemoimmunotherapy to finally elicit a potent antitumor immune response. Such in situ assembly of nanomedicines represents a generalizable strategy towards extracellular drug delivery and cocktail chemoimmunotherapy.

Date: 2022
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DOI: 10.1038/s41467-022-29693-8

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