Biomimetic HDL nanoparticle mediated tumor targeted delivery of indocyanine green for enhanced photodynamic therapy

Colloids Surf B Biointerfaces. 2016 Dec 1:148:533-540. doi: 10.1016/j.colsurfb.2016.09.037. Epub 2016 Sep 26.

Abstract

Photodynamic therapy has emerged as a promising strategy for cancer treatment. To ensure the efficient delivery of a photosensitizer to tumor for anticancer effect, a safe and tumor-specific delivery system is highly desirable. Herein, we introduce a novel biomimetic nanoparticle named rHDL/ICG (rHDL/I), by loading amphiphilic near-infrared (NIR) fluorescent dye indocyanine green (ICG) into reconstituted high density lipoproteins (rHDL). In this system, rHDL can mediate photoprotection effect and receptor-guided tumor-targeting transportation of cargos into cells. Upon NIR irradiation, ICG can generate fluorescent imaging signals for diagnosis and monitoring therapeutic activity, and produce singlet oxygen to trigger photodynamic therapy (PDT). Our studies demonstrated that rHDL/I exhibited excellent size and fluorescence stability, light-triggered controlled release feature, and neglectable hemolytic activity. It also showed equivalent NIR response compared to free ICG under laser irradiation. Importantly, the fluorescent signal of ICG loaded in rHDL/I could be visualized subcellularly in vitro and exhibited metabolic distribution in vivo, presenting superior tumor targeting and internalization. This NIR-triggered image-guided nanoparticle produced outstanding therapeutic outcomes against cancer cells, demonstrating great potential of biomimetic delivery vehicles in future clinical practice.

Keywords: Biomimetic nanoparticle; High density lipoprotein; Photodynamic therapy; Stability; Tumor targeting.

MeSH terms

  • Animals
  • Biomimetic Materials / administration & dosage
  • Biomimetic Materials / chemistry
  • Biomimetic Materials / pharmacokinetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Survival / drug effects
  • Drug Delivery Systems / methods*
  • Drug Liberation
  • Drug Stability
  • Female
  • Hemolysis / drug effects
  • Hep G2 Cells
  • Humans
  • Indocyanine Green / administration & dosage*
  • Indocyanine Green / chemistry
  • Indocyanine Green / pharmacokinetics
  • Infrared Rays
  • Lipoproteins, HDL / administration & dosage*
  • Lipoproteins, HDL / chemistry
  • Lipoproteins, HDL / pharmacokinetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Nanoparticles / ultrastructure
  • Photochemotherapy / methods*
  • Rabbits
  • Reactive Oxygen Species / metabolism
  • Transplantation, Heterologous

Substances

  • Lipoproteins, HDL
  • Reactive Oxygen Species
  • Indocyanine Green