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.

Graphical Abstract

Keywords:

• bacteria-based nanoprobe
• bacteria-mediated synergistic cancer therapy
• nanomedicine
• tumor targeting
• tumor immune microenvironment
• clinical trial

Abbreviations

EPR, Enhanced permeation and retention; NP, Nanoparticle; DDS, Drug delivery systems; TB, Tuberculosis; BCG, Bacilli Calmette-Guérin; TME, Tumor metabolism environment; IFP, Interstitial fluid pressure; TNF-α, Tumor necrosis factor; NO, nitric oxide; PAMP, Pathogen-associated molecular patterns; LPS, lipopolysaccharide; OMV, Outer membrane vesicles; TLR, toll-like receptor; IFN, interferon; BG, Bacterial ghost; DC, dendritic cells; S. Typhimurium, Salmonella enterica serovar Typhimurium; MTD, Maximum tolerated dose; LM, Listeria monocytogenes; InlA, internalin A; InlB, internalin B; ActA, actin assembly-inducing protein; LADD, Live attenuated double-deleted; LMDD, LM ∆dal/∆dat strain; KBMA, Killed but metabolically active; LLO, Listeriolysin O; tLLO, truncated version of LLO; HPV-16, Human papilloma virus-16; C. novyi-NT, Clostridium novyi-NT; HIF-1, hypoxia inducing factor-1; EcN, Escherichia coli Nissle 1917; DOX, Doxorubicin; bsAb, bispecific antibodies; APC, antigen presenting cell; MTB, Magnetotactic bacteria; BMSCT, Bacteria-mediated synergistic cancer therapy; Bif, Bifidobacterium infantis; PDA, polydopamine; PTT, Photothermal therapy; PDT, Photodynamic therapy; ROS, Reactive oxygen species; PTA, Photothermal transduction agent; CaP, Calcium phosphate; OMV^Mel, OMVs encapsulating biopolymer-melanin; HSP, Heat shock protein; PTB, Photothermal bacterium; ZIF-90, Zeolitic imidazole frameworks-90; MB, Methylene blue; ATP, Adenosine triphosphate; V-A-AIF, VNP20009-AbVec-Igκ-AIF; BFGF, Basic fibroblast growth factor; ZOL, zoledronic acid; NSCLC, non-small cell lung cancers; Cy, cyclophosphamide; MPM, Malignant pleural mesothelioma; EGFR, Epidermal growth factor receptor; GMP, Good Manufacturing Practices.

Acknowledgments

Yiping Lu, Nan Mei, Yinwei Ying are co-first authors and Bo Yin and Shun Shen are co-corresponding authors for this review.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no competing interests.

Additional information

Funding

This work has been supported by the National Natural Science Foundation of China (Grant No. 82271966), Shanghai Sailing Program (Grant No. 21YF1404800), Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission (Grant No. 22S31905900), Youth Program of Special Project for Clinical Research of Shanghai Municipal Health Commission Health industry (Grant No. 20204Y0423), Youth Medical Talents—Medical Imaging Practitioner Program (No.3030256001), Shanghai Zhou Liangfu Medical Development Foundation “Brain Science and Brain Diseases Youth Innovation Program” and Shanghai Municipal Science and Technology Major Project (No. 2018SHZDZX01), ZJ Lab, and Shanghai Center for Brain-Inspired Technology. However, these funding sources had no involvement in any processes of the research completion.