Decorating Bacteria with Triple Immune Nanoactivators Generates Tumor‐Resident Living Immunotherapeutics

Abstract

An approach of decorating bacteria with triple immune nanoactivators is reported to develop tumor‐resident living immunotherapeutics. Under cytocompatible conditions, tumor‐specific antigens and checkpoint blocking antibodies are simultaneously conjugated onto bacterial surface and then polydopamine nanoparticles are formed via in situ dopamine polymerization. In addition to serving as a linker, polydopamine with its photothermal effect can repolarize tumor‐associated macrophages to a pro‐inflammatory phenotype. The linked antigens promote the maturation of dendritic cells and generate tumor‐specific immune responses, while the anchored antibodies block immune checkpoints and activate cytotoxic T lymphocytes. Decorated bacteria show spatiotemporal tumor retention and proliferation‐dependent drug release, achieving potent antitumor effects in two antigen‐overexpressing tumor models. This work provides a versatile platform to prepare multimodal and long‐acting therapeutics for cancer immunotherapy.

Engineered Microorganisms for Advancing Tumor Therapy

“…Consequently, continued investigations and experiments assume paramount significance, aiming to deepen our comprehension of the underlying mechanisms, refine treatment protocols, as well as guarantee its safety and efficacy which stand as a pivotal facet of cancer therapy. [103] Copyright 2022, Wiley. b) Genetically encoded E. coli.…”

“…The altered E. coli facilitated the conversion of macrophages from an anti‐inflammatory M2 phenotype to an antitumor M1 phenotype ( Figure a). [ 103 ] Moreover, a gene‐edited Salmonella typhimurium A1‐R can produce specific tumor antigens to stimulate CD8 + T lymphocyte expansion. [ 104 ] In addition, the engineering of bacteria to generate and release immunotherapeutic agents (including chemokines, monoclonal antibodies, and cytokines, among others [ 105 ] ) represents an effective immunotherapy approach.…”

“…reversal of the tumor immunosuppressive microenvironment via repolarization of TAMs, maturation of dendritic cells, and activation of cytotoxic T lymphocytes. Reproduced with permission [103]. Copyright 2022, Wiley.…”

Synergistic Brilliance: Engineered Bacteria and Nanomedicine Unite in Cancer Therapy

“…Recently, Liu et al constructed a trimodal cancer therapy nanosystem using biotherapy, PTT, and immunotherapy. [205] In this nanosystem, a polydopamine layer was coated on the outer surface of E. coli Nissle 1917 via in situ co-deposition polymerization. Subsequently, the tumor-specific antigen ovalbumin and immune checkpoint inhibitor PD-1 antibody were conjugated onto the surface of this nanobiohybrid to form polydopamine nanoparticles.…”

“…thus achieving interpromotion between both to maximize the cooperative therapeutic effect. Generally, the reinforcement effects between engineered bacteria and nanomedicine could be summarized as follows: (1) the tumor targeting ability of bacteria could be further enhanced through modifying aptamer/antibodysupported nanomedicine; (2) the optical and energy conversion properties of nanomedicine could be employed to con-trol/regulate the production of anticancer microbial agents; (3) the introduction of nanomedicine increases the lytic efficiency of cancer cells, which allows the bacteria to proliferate rapidly due to the extra nutrients; (4) some nanomedicine could increase the survival rate of bacteria and the antigen presentation efficiency, thereby improving the therapeutic effect of cancer biotherapy; (5) the catalytic activity and electron transport [205] Copyright 2022, Wiley-VCH. characteristics of nanomedicine can accelerate the metabolism rate of bacteria, thus enhancing the anticancer efficiency; (6) the decoration of nanomedicine on the surface of bacteria could substantially increase the deposition efficiency of nanomedicine in the tumor site and hypoxic areas; (7) some natural bacteria are able to produce substrates for nanomedicine-mediated cancer therapy, such as photosynthetic bacteria producing O 2 to promote PDT and SDT; and (8) bacteria-based biotherapy could improve nanomedicine-mediated cancer therapies, such as chemotherapy, immunotherapy, and PTT, through TME modulation, for example, bacteria can secrete interfering RNA to reverse the drug resistance of cancer cells, thereby enhancing the effect of chemotherapy.…”