4.7 Article

Bacteria-driven hypoxia targeting delivery of chemotherapeutic drug proving outcome of breast cancer

Journal

JOURNAL OF NANOBIOTECHNOLOGY
Volume 20, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12951-022-01373-1

Keywords

Biohybrid; Bifidobacterium infantis; Tumor hypoxia; Albumin nanoparticles; Breast cancer

Funding

  1. Project Program of the Science and Technology Department of Sichuan Province [2020YJ0385]
  2. Open Project Program of Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province [HYX-19009]
  3. Youth Fund Projects of Southwest Medical University [2020ZRQNA028]
  4. Key Project of Southwest Medical University [2021ZKZD014]

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Local hypoxia is a common feature of solid tumors. In this study, a biocompatible bacteria/nanoparticles biohybrid platform was developed to target breast tumors. The results showed that the biohybrid was able to effectively colonize hypoxic tumors, increasing drug accumulation and reducing toxic side-effects.
Local hypoxia is a common feature of many solid tumors and may lead to unsatisfactory chemotherapy outcomes. Anaerobic bacteria that have an affinity to hypoxic areas can be used to achieve targeted drug delivery in tumor tissues. In this study, we developed a biocompatible bacteria/nanoparticles biohybrid (Bif@DOX-NPs) platform that employs the anaerobic Bifidobacterium infantis (Bif) to deliver adriamycin-loaded bovine serum albumin nanoparticles (DOX-NPs) into breast tumors. The Bif@DOX-NPs retained the targeting ability of B. infantis to hypoxic regions, as well as the cytotoxicity of DOX. The biohybrids were able to actively colonize the hypoxic tumors and significantly increased drug accumulation at the tumor site. The DOX concentration in the tumor masses colonized by Bif@DOX-NPs was 4 times higher than that in the free DOX-treated tumors, which significantly prolonged the median survival of the tumor-bearing mice to 69 days and reduced the toxic side-effects of DOX. Thus, anaerobic bacteria-based biohybrids are a highly promising tool for the targeted treatment of solid tumors with inaccessible hypoxic regions.

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