Anaerobe-Inspired Anticancer Nanovesicles

Angew Chem Int Ed Engl. 2017 Mar 1;56(10):2588-2593. doi: 10.1002/anie.201611783. Epub 2017 Jan 31.

Abstract

Anaerobic bacteria, such as Clostridium and Salmonella, can selectively invade and colonize in tumor hypoxic regions (THRs) and deliver therapeutic products to destroy cancer cells. Herein, we present an anaerobe nanovesicle mimic that can not only be activated in THRs but also induce hypoxia in tumors by themselves. Moreover, inspired by the oxygen metabolism of anaerobes, we construct a light-induced hypoxia-responsive modality to promote dissociation of vehicles and activation of bioreductive prodrugs simultaneously. In vitro and in vivo experiments indicate that this anaerobe-inspired nanovesicle can efficiently induce apoptotic cell death and significantly inhibit tumor growth. Our work provides a new strategy for engineering stimuli-responsive drug delivery systems in a bioinspired and synergistic fashion.

Keywords: drug delivery; nanomedicines; photodynamic therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Death / drug effects
  • Cell Proliferation / drug effects
  • Clostridium / chemistry*
  • Clostridium / metabolism
  • Drug Carriers / chemistry
  • Drug Carriers / metabolism
  • Drug Delivery Systems
  • Drug Screening Assays, Antitumor
  • Humans
  • Hypoxia / metabolism*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • Nanoparticles / chemistry*
  • Prodrugs / chemistry
  • Prodrugs / pharmacology*
  • Salmonella / chemistry*
  • Salmonella / metabolism
  • Tirapazamine / chemistry
  • Tirapazamine / pharmacology

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Imidazoles
  • Prodrugs
  • Tirapazamine