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Enhancing anti‐PD‐1 Immunotherapy by Nanomicelles Self‐Assembled from Multivalent Aptamer Drug Conjugates
Author(s) -
Geng Zhongmin,
Wang Lu,
Liu Ke,
Liu Jinyao,
Tan Weihong
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202102631
Subject(s) - aptamer , conjugate , amphiphile , polyethylene glycol , chemistry , drug , peg ratio , combinatorial chemistry , drug carrier , biophysics , drug delivery , pharmacology , cancer research , biochemistry , copolymer , microbiology and biotechnology , medicine , biology , polymer , organic chemistry , mathematical analysis , mathematics , finance , economics
A tumor‐targeting enhanced chemotherapy, enabled by aptamer‐drug conjugate nanomicelles, is reported that boosts antitumor immune responses. Multivalent aptamer drug conjugate (ApMDC), an amphiphilic telodendrimer consisting of a hydrophilic aptamer and a hydrophobic monodendron anchored with four anticancer drugs by acid‐labile linkers, was designed and synthesized. By co‐self‐assembly with an ApMDC analogue, in which aptamer is replaced with polyethylene glycol, the surface aptamer density of these nanomicelles can be screened to reach an optimal complementation between blood circulation and tumor‐targeting ability. Optimized nanomicelles can enhance immunogenic cell death of tumor cells, which strikingly augments the tumor‐specific immune responses of the checkpoint blockade in immunocompetent tumor‐bearing mice. ApMDC nanomicelles represent a robust platform for structure–function optimization of drug conjugates and nanomedicines.