4.8 Article

Bacterial-based cancer therapy: An emerging toolbox for targeted drug/gene delivery

Journal

BIOMATERIALS
Volume 277, Issue -, Pages -

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.121124

Keywords

Bacterial carrier; Targeting delivery; Genetic engineering; Biomaterials; Cancer theranostics

Funding

  1. National Natural Science Foundation of China [81972900, 61905137]
  2. Natural Science Foundation of Shaanxi Province [2020JQ-411, 2020JM-275]
  3. China Postdoctoral Science Foundation [2019M653862XB]
  4. Fundamental Research Funds for the Central Universities [GK202105004, GK202003057]

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Bacteria are increasingly being considered for targeted tumor therapy due to their intrinsic tumor tropism and ability to rapidly colonize in the favorable TME. Compared to other nano-strategies, tumor-targeting bacteria are largely unaffected by the tumor cells and microenvironment. Integration of live bacteria with anti-cancer drugs and nanomaterials can enhance targeted delivery and accumulation in tumors.
Precise targeting and high therapeutic efficiency are the major requisites of personalized cancer treatment. However, some unique features of the tumor microenvimnment (TME) such as hypoxia, low pH and elevated interstitial fluid pressure cause cancer cells resistant to most therapies. Bacteria are increasingly being considered for targeted tumor therapy owing to their intrinsic tumor tropism, high motility as well as the ability to rapidly colonize in the favorable TME. Compared to other nano-strategies using peptides, aptamers, and other biomolecules, tumor-targeting bacteria are largely unaffected by the tumor cells and microenvironment. On the contrary, the hypoxic TME is highly conducive to the growth of facultative anaerobes and obligate anaerobes. Live bacteria can be further integrated with anti-cancer drugs and nanomaterials to increase the latter's targeted delivery and accumulation in the tumors. Furthermore, anaerobic and facultatively anaerobic bacteria have also been combined with other anti-cancer therapies to enhance therapeutic effects. In this review, we have summarized the applications and advantages of using bacteria for targeted tumor therapy (Scheme 1) in order to aid in the design of novel intelligent drug delivery systems. The current challenges and future prospects of tumor-targeting bacterial nanocarriers have also been discussed.

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