Zinc pthalocyanine-loaded chitosan/mPEG-PLA nanoparticles-mediated photodynamic therapy for the treatment of cutaneous squamous cell carcinoma

J Biophotonics. 2018 Nov;11(11):e201800114. doi: 10.1002/jbio.201800114. Epub 2018 Jul 13.

Abstract

Zinc pthalocyanine (ZnPc) is a second-generation photodynamic therapy (PDT) sensitizer with sufficient PDT activity for squamous cell carcinoma (SCC). ZnPc is hydrophobic and insoluble in water, which creates hurdles in systemic administration and hence restricts its use in clinic. Here we have loaded ZnPc on chitosan/methoxy polyethylene glycol-polylactic acid (CPP) nanoparticles to form Z-CPP to enhance PDT efficacy. In vitro and in vivo studies were performed to see dark toxicity of the compounds ZnPc, CPP and Z-CPP. Then PDT was done and its growth inhibitory effect on SCC cells was evaluated. In addition, reactive oxygen species (ROS) formation and apoptosis of cancer cells following PDT were studied. The results showed that the tested compounds exhibit no dark toxicity and the effect of PDT was significantly better with Z-CPP when compared to free ZnPc (P < .05). Photoactivation of Z-CPP led to a dose-dependent growth inhibition of cancer cells of >50% at 1 μM to >80% at 10 μM concentration. Also Z-CPP-treated cells had highest number of apoptotic cells and produced more ROS compared to free ZnPc-treated cells (P < .05). Hence, this study suggests that Z-CPP is a suitable pharmaceutical compound to increase PDT efficacy.

Keywords: chitosan/mPEG-PLA; nanoparticles; photodynamic therapy; photosensitizer; squamous cell carcinoma; zinc pthalocyanine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Chitosan / chemistry*
  • Drug Carriers / chemistry
  • Humans
  • Mice
  • Nanoparticles / chemistry*
  • Photochemotherapy*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Polyesters / chemistry*
  • Polyethylene Glycols / chemistry*
  • Reactive Oxygen Species / metabolism
  • Safety
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Zinc / chemistry*

Substances

  • Drug Carriers
  • Photosensitizing Agents
  • Polyesters
  • Reactive Oxygen Species
  • methoxy poly(ethylene glycol)-poly(lactide)
  • Polyethylene Glycols
  • Chitosan
  • Zinc