Despite bacterial-mediated biotherapies have been widely explored for treating different types of cancer, their implementation has been restricted by low treatment efficacy, due largely to the absence of tumor-specific accumulation following administration. Here, the conjugation of aptamers to bacterial surface is described by a simple and cytocompatible amidation procedure, which can significantly promote the localization of bacteria in tumor site after systemic administration. The surface density of aptamers can be easily adjusted by varying feed ratio and the conjugation is able to increase the stability of anchored aptamers. Optimal bacteria conjugated with an average of 2.8 × 105 aptamers per cell present the highest specificity to tumor cells in vitro, separately generating near 2- and 4-times higher accumulation in tumor tissue at 12 and 60 hours compared to unmodified bacteria. In both 4T1 and H22 tumor-bearing mouse models, aptamer-conjugated attenuated Salmonella show enhanced antitumor efficacy, along with highly activated immune responses inside the tumor. This work demonstrates how bacterial behaviors can be tuned by surface conjugation and supports the potential of aptamer-conjugated bacteria for both targeted intratumoral localization and enhanced tumor biotherapy.
Atumor-targeting enhanced chemotherapy, enabled by aptamer-drug conjugate nanomicelles,i sr eported that boosts antitumor immune responses.Multivalent aptamer drug conjugate (ApMDC), an amphiphilic telodendrimer consisting of ah ydrophilic aptamer and ah ydrophobic monodendron anchored with four anticancer drugs by acid-labile linkers,was designed and synthesized. By co-self-assembly with an ApMDC analogue,i nw hich 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.O ptimized nanomicelles can enhance immunogenic cell death of tumor cells,w hichs trikingly augments the tumor-specific immune responses of the checkpoint blockade in immunocompetent tumor-bearing mice.A pMDC nanomicelles represent ar obust platform for structure-function optimization of drug conjugates and nanomedicines.
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