Polyethylene glycol modified ORMOSIL theranostic nanoparticles for triggered doxorubicin release and deep drug delivery into ovarian cancer spheroids

J Photochem Photobiol B. 2017 Sep;174:209-216. doi: 10.1016/j.jphotobiol.2017.07.020. Epub 2017 Jul 27.

Abstract

A novel pegylated multifunctional probe of Ormosil nanoparticles (PEGCDSIR820) loaded with Near Infrared dye (NIR; IR820) and a chemotherapeutic drug, Doxorubicin (DOX) was developed for cancer theranostic applications. PEGCDSIR820 nanoparticles had an average diameter of 58.2±3.1nm, zeta potential of -6.9±0.1mV in cell culture media and stability against aggregation in physiological buffers. The encapsulation efficiency of DOX was 65.0±3.0%, and that of IR820 was 76.0±2.1%. PEGCDSIR820 showed no cytotoxicity in ovarian cancer cells (Skov-3). The cytotoxicity markedly increased when Skov-3 cells incubated with PEGCDSIR820 particles were exposed to 808nm laser due to the combination of adjuvant hyperthermia (43°C) and enhanced DOX release. Exposure to laser enhanced the release of DOX, 45% of DOX release was observed in 3h compared to 23% without laser exposure. Confocal imaging in Skov-3 cells showed that the combination of hyperthermia due to NIR exposure and release of DOX caused cell necrosis. Furthermore, in spheroids exposed to NIR laser penetration of DOX was deeper compared to the absence of laser exposure. Skov-3 spheroids incubated with pegylated nanoparticles for 24h and exposed to laser showed 94% reduction in cell viability. Encapsulation of IR820 in PEGCDSIR820 increased the in-vivo elimination half-life to 41.0±7.2h from 30.5±0.5h of free IR820.

Keywords: Cancer spheroids; Chemotherapy; Hyperthermia; Nanoparticles; Near infrared; Theranostics.

MeSH terms

  • Cell Line, Tumor
  • Doxorubicin / chemistry*
  • Doxorubicin / metabolism
  • Doxorubicin / pharmacology
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacokinetics
  • Drug Liberation*
  • Female
  • Humans
  • Kinetics
  • Nanoparticles / chemistry*
  • Ovarian Neoplasms / pathology*
  • Particle Size
  • Polyethylene Glycols / chemistry*
  • Siloxanes / chemistry*
  • Spheroids, Cellular / metabolism*
  • Temperature
  • Theranostic Nanomedicine
  • Tissue Distribution

Substances

  • Drug Carriers
  • Siloxanes
  • ormosil
  • Polyethylene Glycols
  • Doxorubicin