Enhancing anti-PD-1 immunotherapy by nanomicelles self-assembled from aptamer-multivalent-drug conjugates.

Here, a tumor-targeting yet enhanced chemotherapy enabled by aptamer-drug conjugate nanomicelles is reported to boost antitumor immune responses. Aptamer-multivalent-drug conjugate (ApMDC), an amphiphilic telodendrimer consisting of a hydrophilic aptamer and a hydrophobic monodendron anchored with four anticancer drugs by acid-labile linkers, is designed and synthesized. By co-self-assembly with an ApMDC analogue, in which aptamer is replaced with polyethylene glycol, 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 tumor-specific immune responses of checkpoint blockade in immunocompetent tumor-bearing mice. ApMDC nanomicelles represent a robust platform for structure-function optimization of drug conjugates and nanomedicines, suggesting an alternative to improve antitumor efficacy.