Photosensitizer-Loaded Multifunctional Chitosan Nanoparticles for Simultaneous in Situ Imaging, Highly Efficient Bacterial Biofilm Eradication, and Tumor Ablation

ACS Appl Mater Interfaces. 2019 Jan 16;11(2):2302-2316. doi: 10.1021/acsami.8b19522. Epub 2018 Dec 31.

Abstract

In recent decades, bacterial and viral infections and chronic inflammatory response have emerged as important causes of cancer. Also, infections remain a significant cause of morbidity and mortality in cancer patients. In this work, carboxymethyl chitosan nanoparticles (CMC NPs) were synthesized in a facile and green way and further combined with ammonium methylbenzene blue (MB) as a cross-linking agent as well as a fluorescent molecule and a photosensitizer for self-imaging photodynamic therapy (PDT). The obtained CMC-MB NPs exhibited an apparent pH-responsive release behavior of MB, which was released for a prolonged period in a simulated physiological environment (pH 7.4) for more than 15 days and the time reduced to only 3.5 h in acidic conditions (pH 5.5). When irradiated by a 650 nm laser at 202 mW/cm2 for 5 min, the CMC-MB NPs showed efficient bactericidal and biofilm eradication properties as well as suppression of tumor cell growth in a similar acidified microenvironment. Furthermore, in an in vivo rabbit wound bacterial infection model, the rapid sterilization of CMC-MB NPs played a crucial role in bacterial infections, inflammation inhibition, and wound healing. As a PDT treatment against cancer, the CMC-MB NPs also exhibited an efficient antitumor therapeutic effect in a subcutaneous tumor mice model.

Keywords: bacterial infections; biofilms; cancer; in vivo; photodynamic therapy.

MeSH terms

  • Animals
  • Bacteria / growth & development*
  • Bacterial Infections / drug therapy*
  • Bacterial Infections / metabolism
  • Bacterial Infections / pathology
  • Bacterial Physiological Phenomena* / drug effects
  • Bacterial Physiological Phenomena* / radiation effects
  • Biofilms* / drug effects
  • Biofilms* / growth & development
  • Biofilms* / radiation effects
  • Cell Line, Tumor
  • Chitosan / analogs & derivatives*
  • Chitosan / chemistry
  • Chitosan / pharmacology
  • Humans
  • Mice
  • Mice, Nude
  • Nanoparticles* / chemistry
  • Nanoparticles* / therapeutic use
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Photochemotherapy*
  • Photosensitizing Agents* / chemistry
  • Photosensitizing Agents* / pharmacology
  • Rabbits
  • Xenograft Model Antitumor Assays

Substances

  • Photosensitizing Agents
  • carboxymethyl-chitosan
  • Chitosan