Enhancing anti‐PD‐1 Immunotherapy by Nanomicelles Self‐Assembled from Multivalent Aptamer Drug Conjugates

作者：Zhongmin Geng, Lu Wang, Ke Liu, Jinyao Liu, Weihong Tan · 发表于：Angewandte Chemie International Edition · 年份：2021 · DOI：10.1002/anie.202102631 · 被引用次数：85 · 研究领域：Nanoplatforms for cancer theranostics、Advanced biosensing and bioanalysis techniques、Supramolecular Self-Assembly in Materials

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.