A hyaluronic acid nanogel for photo-chemo theranostics of lung cancer with simultaneous light-responsive controlled release of doxorubicin

Nanoscale. 2015 Jun 28;7(24):10680-9. doi: 10.1039/c5nr01075f. Epub 2015 Jun 1.

Abstract

The combined delivery of photo- and chemo-therapeutic agents is an emerging strategy to overcome drug resistance in treating cancer, and controlled light-responsive drug release is a proven tactic to produce a continuous therapeutic effect for a prolonged duration. Here, a combination of light-responsive graphene, chemo-agent doxorubicin and pH-sensitive disulfide-bond linked hyaluronic acid form a nanogel (called a graphene-doxorubicin conjugate in a hyaluronic acid nanogel) that exerts an activity with multiple effects: thermo and chemotherapeutic, real-time noninvasive imaging, and light-glutathione-responsive controlled drug release. The nanogel is mono-dispersed with an average diameter of 120 nm as observed by using TEM and a hydrodynamic size analyzer. It has excellent photo-luminescence properties and good stability in buffer and serum solutions. Graphene itself, being photoluminescent, can be considered an optical imaging contrast agent as well as a heat source when excited by laser irradiation. Thus the nanogel shows simultaneous thermo-chemotherapeutic effects on noninvasive optical imaging. We have also found that irradiation enhances the release of doxorubicin in a controlled manner. This release synergizes therapeutic activity of the nanogel in killing tumor cells. Our findings demonstrate that the graphene-doxorubicin conjugate in the hyaluronic acid nanogel is very effective in killing the human lung cancer cell line (A549) with limited toxicity in the non-cancerous cell line (MDCK).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / chemistry
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Cell Line, Tumor
  • Chemoradiotherapy / methods
  • Contrast Media
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / chemical synthesis
  • Diffusion
  • Doxorubicin / administration & dosage*
  • Doxorubicin / chemistry
  • Doxorubicin / radiation effects
  • Graphite / radiation effects
  • Graphite / therapeutic use
  • Humans
  • Hyaluronic Acid / chemistry*
  • Light
  • Nanocapsules / administration & dosage
  • Nanocapsules / chemistry*
  • Nanocapsules / ultrastructure
  • Nanoconjugates / administration & dosage
  • Nanoconjugates / chemistry
  • Nanogels
  • Neoplasms, Experimental / pathology*
  • Neoplasms, Experimental / therapy*
  • Photochemotherapy / methods*
  • Polyethylene Glycols / chemistry
  • Polyethyleneimine / chemistry
  • Theranostic Nanomedicine
  • Treatment Outcome

Substances

  • Antibiotics, Antineoplastic
  • Contrast Media
  • Delayed-Action Preparations
  • Nanocapsules
  • Nanoconjugates
  • Nanogels
  • polyethylene glycol polyethyleneimine nanogel
  • Polyethylene Glycols
  • Graphite
  • Doxorubicin
  • Polyethyleneimine
  • Hyaluronic Acid