Facile development of biodegradable polymer-based nanotheranostics: Hydrophobic photosensitizers delivery, fluorescence imaging and photodynamic therapy

J Photochem Photobiol B. 2019 Apr:193:39-50. doi: 10.1016/j.jphotobiol.2019.02.007. Epub 2019 Feb 21.

Abstract

Photodynamic therapy (PDT) is reported to be a promising technique to eradicate various cancers. As most of the photosensitizers (PSs) are hydrophobic in nature, thus, the effective delivery of PSs at the targeted site is the main hurdle associated with PDT. Zinc phthalocyanine and Zinc naphthalocyanine are reported as good PSs, however, highly hydrophobic characteristics restrict their use for clinical applications. To circumvent this limitation here we developed the advanced polymer-based nano-delivery system having polyethylene glycol (PEG) coated polymeric core with ~90% PS encapsulation. The PEG coating was responsible for the stabilization of probe in the physiological environment and storage conditions. The developed theranostic probes showed efficient in vitro fluorescence and singlet oxygen quantum yields upon irradiation with 620-750 nm (30 mW/cm2) light. The clathrin-mediated endocytosis (CME) based mechanism of cellular internalization was evaluated. The fluorescence of treated MCF-7 cells showed the ability of the probes as imaging agents. Moreover, up to 65% cell inhibition showed their cytotoxic efficiency. Further, comparatively higher tumor-accumulation of PSs without significant hepato/nephro-toxicity shown in vivo experimentation using breast tumor-bearing female Sprague Dawley (SD) rats suggested the featured passive targeting ability of preparations and clinically safe to be used. The study explored the exceptional delivery system for hydrophobic PSs with commendable theranostic applications.

Keywords: Fluorescence imaging; PLGA nanoparticles; Photodynamic therapy (PDT); Photomedicine; Theranostics.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Drug Carriers / chemistry
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Indoles / chemistry
  • Indoles / pharmacology
  • Indoles / therapeutic use
  • Isoindoles
  • MCF-7 Cells
  • Microscopy, Confocal
  • Nanoparticles / chemistry
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology
  • Organometallic Compounds / therapeutic use
  • Photochemotherapy
  • Photosensitizing Agents / chemistry*
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Polyethylene Glycols / chemistry
  • Polymers / chemistry*
  • Rats
  • Rats, Sprague-Dawley
  • Singlet Oxygen / metabolism
  • Theranostic Nanomedicine*
  • Transplantation, Heterologous
  • Zinc Compounds

Substances

  • Drug Carriers
  • Indoles
  • Isoindoles
  • Organometallic Compounds
  • Photosensitizing Agents
  • Polymers
  • Zinc Compounds
  • zinc naphthalocyanine
  • Zn(II)-phthalocyanine
  • Singlet Oxygen
  • Polyethylene Glycols