Squalene-PEG: Pyropheophorbide-a nanoconstructs for tumor theranostics

Nanomedicine. 2019 Jan;15(1):243-251. doi: 10.1016/j.nano.2018.09.013. Epub 2018 Oct 7.

Abstract

Novel nanoscale drug delivery biomaterials are of great importance for the diagnosis and treatment of different cancers. We have developed a new pegylated squalene (SQ-PEG) derivative with self-assembly properties. Supramolecular assembly with a lipophilic photosensitizer pyropheophorbide-a (Ppa) by nanoprecipitation gave nanoconstructs SQ-PEG:Ppa with an average size of 200 nm in diameter and a drug loading of 18% (w/w). The composite material demonstrates nanoscale optical properties by tight packing of Ppa within Sq-PEG:Ppa resulting in 99.99% fluorescence self-quenching. The biocompatibility of the nanomaterial and cell phototoxicity under light irradiation were investigated on PC3 prostate tumor cells in vitro. SQ-PEG:Ppa showed excellent phototoxic effect at low light dose of 5.0 J/cm2 as a consequence of efficient cell internalization of Ppa by the nanodelivery system. The diagnostic potential of SQ-PEG:Ppa nanoconstructs to deliver Ppa to tumors in vivo was demonstrated in chick embryo model implanted with U87MG glioblastoma micro tumors.

Keywords: Fluorescence photodiagnosis; Nanoconstructs; Photodynamic therapy; Pyropheophorbide-a; Self-assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Chick Embryo
  • Chlorophyll / analogs & derivatives*
  • Chlorophyll / chemistry
  • Chorioallantoic Membrane / drug effects
  • Drug Delivery Systems
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Light
  • Male
  • Mice
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Photochemotherapy
  • Photosensitizing Agents / administration & dosage*
  • Photosensitizing Agents / chemistry
  • Polyethylene Glycols / chemistry
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Squalene / administration & dosage*
  • Squalene / chemistry
  • Theranostic Nanomedicine*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Photosensitizing Agents
  • Chlorophyll
  • pyropheophorbide a
  • Polyethylene Glycols
  • Squalene