Nanotechnology-Employed Bacteria-Based Delivery Strategy for Enhanced Anticancer Therapy

Abstract

Bacteria and their derivatives (membrane vesicles, MVs) exhibit great advantages for targeting hypoxic tumor cores, strong penetration ability and activating immune responses, holding great potential as auspicious candidates for therapeutic and drug-delivery applications. However, the safety issues and low therapeutic efficiency by single administration still need to be solved. To further optimize their performance and to utilize their natural abilities, scientists have strived to modify bacteria with new moieties on their surface while preserving their advantages. The aim of this review is to give a comprehensive overview of a non-genetic engineering modification strategy that can be used to optimize the bacteria with nanomaterials and the design strategy that can be used to optimize MVs for better targeted therapy. Here, the advantages and disadvantages of these processes and their applicability for the development of bacteria-related delivery system as antitumor therapeutic agents are discussed. The prospect and the challenges of the above targeted delivery system are also proposed.

Bacterial outer membrane vesicles as a candidate tumor vaccine platform

“…Although this level of expression is sufficient to activate the immune response, increasing expression can help transmit more antigen to APCs and thereby enhance the response. Further, the composition of OMVs may result in the host body producing an unexpected response, which can overshadow the desired immune response and reduce the specific response to the target antigen (81). Therefore, it is necessary to strike a balance between eliciting the immune response and the efficiency of antigen presentation (5).…”

The Role of Hitchhiking in Cancer Therapeutics—A Review

“…The bacteriaassisted transfer has a myriad of benefits, such as the capacity to address hypoxic tumor bulk, infiltrate extensively, and activate the immune function, making it an attractive alternative for therapeutic cargo administration. [173] Researchers have sought to improve bacteria with novel elements on its exterior while retaining existing benefits in order to enhance productivity and harness their inherent qualities. [35] Nevertheless, the safety difficulties and narrow therapeutic efficacy have been noticeably enhanced thanks to numerous genetic modification techniques.…”

“…As a consequence, the hitchhiked system offers a "cloaking" strategy to counteract inflammatory processes by modulating nanomaterial on the exterior of bacteria. [173] Furthermore, by integrating therapeutic cargos with the motile bacterium, the hitchhiking system utilizes the guidance of targeting bacteria to convey chemotherapeutic payload to malignant cells. [175,176] After delivery to the tumor, payloads would be smartly released selectively within the tumor to ensure optimum productivity and minimal adverse effects.…”

“…As a consequence, the hitchhiked system offers a “cloaking” strategy to counteract inflammatory processes by modulating nanomaterial on the exterior of bacteria. [ 173 ]…”

Recent advances in bacteria-mediated cancer therapy

“…In particular, the inherent tropism of bacteria for different types of tumors and their ability to overcome the vascular barrier means that they have potential for use in tumor-targeting delivery ( Wu et al, 2021 ). Furthermore, the cell surfaces of bacteria can be decorated with organic or inorganic materials, including various types of nanomaterial and therapeutic agents for cargo delivery ( Zhu C. et al, 2021 ; Ye et al, 2021 ; Jiménez-Jiménez et al, 2022 ). Additionally, bacterial derivatives—including outer membrane vesicles (OMVs), minicells, and bacterial protoplast-derived nanovesicles—have been shown to have great potential as safe and efficient drug carriers ( Ali et al, 2020 ).…”