Bacteria-Based Nanoprobes for Cancer Therapy

Abstract

Surgical removal together with chemotherapy and radiotherapy has used to be the pillars of cancer treatment. Although these traditional methods are still considered as the first-line or standard treatments, non-operative situation, systemic toxicity or resistance severely weakened the therapeutic effect. More recently, synthetic biological nanocarriers elicited substantial interest and exhibited promising potential for combating cancer. In particular, bacteria and their derivatives are omnipotent to realize intrinsic tumor targeting and inhibit tumor growth with anti-cancer agents secreted and immune response. They are frequently employed in synergistic bacteria-mediated anticancer treatments to strengthen the effectiveness of anti-cancer treatment. In this review, we elaborate on the development, mechanism and advantage of bacterial therapy against cancer and then systematically introduce the bacteria-based nanoprobes against cancer and the recent achievements in synergistic treatment strategies and clinical trials. We also discuss the advantages as well as the limitations of these bacteria-based nanoprobes, especially the questions that hinder their application in human, exhibiting this novel anti-cancer endeavor comprehensively.

Keywords: bacteria-based nanoprobe; bacteria-mediated synergistic cancer therapy; clinical trial; nanomedicine; tumor immune microenvironment; tumor targeting.

Graphical abstract

Figure 1

Schematic diagram shows the construction of the Bif@PDA-PTX-NPs biohybrid and its intelligent responsibility to reductive tumor microenvironment through self-driven targeting to hypoxic regions of tumor.

Figure 2

Schematic illustration depicting the construction of the minicellspHLIP for targeted delivery of chemotherapeutic drugs into the hypoxic regions of solid tumors to kill cancer cells.

Figure 3

OMV@CaPs for enabling efficient tumor accumulation and overcoming the severe inflammatory effect.

Figure 4

Schematic illustration of (A) synthetic procedure of ZIF-90/MB, and (B) synthetic procedure of PTB and PTB@ZIF-90/MB, and (C) mechanism of tumor targeting and photothermal tumor ablation of PTB@ZIF-90/MB upon laser irradiation.

Figure 5

Tum-5 protein (yellow) could be solubly expressed in EcN and secreted to the medium. The engineered bacteria (blue) were rapidly specially colonized in mouse tumors. Tum-5 bound to integrin receptors on the surface of vascular endothelial cells to induce endothelial cell apoptosis. This process would cause blood vessels to shrink, then the tumor growth was suppressed.

Figure 6

Schematic illustration depicts the mechanism by which gut microbiota (Bifidobacterium) preferentially colonize in tumor sites and facilitate immunotherapy via STING signaling.