Entirely Synthetic Bacterial Nanomimics for Highly-Effective Tumor Suppression and Immune Elicitation

Bacteria are considered to be perfect anticancer agents on account of their unique capabilities of specific tumor targeting, active intratumoral penetration and controllable cytotoxicity induction, but so far there is no great success in clinical translations due to many challenging issues including intrinsic bacterial toxicity, potential immunogenicity and safety concerns. To address this dilemma, an artificial bacterial nanomimic (BNM) consisted of biocompatible multifunctional peptide dendrimers and a polysaccharide was exploited to imitate the structure and function of bacteria. The resulted BNMs could recognize and bind with the sialic acid (SA) moieties on cell surface, thereby achieving improved cellular uptake and intratumoral penetration. Light activated BNMs caused distinct tumor cell apoptosis and necrosis through greatly up-regulating the intracellular ROS level, evidenced with oxidative damage of lysosomes, cathepsin release and cell death. Meanwhile, both the BNMs and antigens releasing from dying cells significantly promoted the maturation of dendritic cells and secretion of pro-inflammatory cytokines, which further improved the antitumor effect. Encouragingly, light activated BNMs displayed excellent tumor suppression capacity and completely eliminated two tumors, and significantly prolonged the survival time. This study provides a new strategy for engineering therapeutic agents in a bioinspired fashion. (C) 2020 Elsevier Ltd. All rights reserved.