Bacteria-Driven Tumor Microenvironment-Sensitive Nanoparticles Targeting Hypoxic Regions Enhances the Chemotherapy Outcome of Lung Cancer

Int J Nanomedicine. 2023 Mar 15:18:1299-1315. doi: 10.2147/IJN.S396863. eCollection 2023.

Abstract

Background: Chemotherapy still plays a dominant role in cancer treatment. However, the inability of conventional chemotherapeutic drugs to reach the hypoxic zone of solid tumors significantly weakens their efficacy. Bacteria-mediated drug delivery systems can be an effective targeting strategy for improving the therapeutic outcomes in cancer. Anaerobic bacteria have the unique ability to selectively transport drug loads to the hypoxic regions of tumors.

Methods: We designed a Bifidobacterium infantis (Bif)-based biohybrid (Bif@PDA-PTX-NPs) to deliver polydopamine (PDA)-coated paclitaxel nanoparticles (PTX-NPs) to tumor tissues.

Results: The self-driven Bif@PDA-PTX-NPs maintained the toxicity of PTX as well as the hypoxic homing tendency of Bif. Furthermore, Bif@PDA-PTX-NPs significantly inhibited the growth of A549 xenografts in nude mice, and prolonged the survival of the tumor-bearing mice compared to the other PTX formulations without any systemic or localized toxicity.

Conclusion: The Bif@PDA-PTX-NPs biohybrids provide a new therapeutic strategy for targeted chemotherapy to solid tumors.

Keywords: bifidobacterium infantis; lung cancer; nanoparticles; paclitaxel; tumor hypoxia.

MeSH terms

  • Animals
  • Bacteria
  • Cell Line, Tumor
  • Drug Delivery Systems
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles*
  • Paclitaxel / therapeutic use
  • Tumor Microenvironment

Substances

  • Paclitaxel

Grants and funding

This study is supported by grants from the Science and Technology Department of Sichuan Province (2020YJ0385, 2022YFS0623-C2), the Key Project of Southwest Medical University (No. 2021ZKZD014), the Youth Fund Projects of Southwest Medical University (No. 2020ZRQNA028), the Science and Technology Project of Luzhou (2022-JYJ-139, 2017LZXNYD-Z04).