Peptide grafted and self-assembled poly(γ-glutamic acid)-phenylalanine nanoparticles targeting camptothecin to glioma

Nanomedicine (Lond). 2017 Jul;12(14):1661-1674. doi: 10.2217/nnm-2017-0067. Epub 2017 Jun 21.

Abstract

Aim: To synthesize cRGDfK peptide conjugated poly(γ-glutamic acid)-phenylalanine nanoparticles to improve the therapeutic efficacy of camptothecin (CPT) against glioblastoma multiforme.

Methods: Peptide-conjugated, drug-loaded nanoparticles (cRGDfK-conjugated camptothecin-loaded PGA-PA nanoparticles [RCPN]) were prepared and physico-chemically characterized using different techniques. Nanoparticles were evaluated for in vitro anticancer activity, cellular uptake, induction of apoptosis and wound healing cell migration against U87MG human glioblastoma cells.

Results: RCPN, with a particle size of <100 nm and 65% CPT encapsulation efficiency, exhibited a dose- and time-dependent cytotoxicity to glioblastoma cells. Compared with native CPT or unconjugated nanoparticles, RCPN induced apoptosis, increased reactive oxygen species generation and inhibited U87MG cell migration.

Conclusion: cRGDfK-mediated and amphiphilic copolymer-based nanomedicines represent a new approach for improved delivery of anticancer drugs to and treatment of glioblastoma multiforme.

Keywords: anticancer activity; cRGDfK; camptothecin; glioblastoma multiforme; phenylalanine; poly(γ-glutamic acid).

MeSH terms

  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Brain / drug effects
  • Brain / pathology
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Camptothecin / administration & dosage*
  • Camptothecin / pharmacology
  • Cell Line, Tumor
  • Drug Delivery Systems
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Humans
  • Nanoconjugates / chemistry*
  • Peptides, Cyclic / chemistry*
  • Phenylalanine / chemistry*
  • Polyglutamic Acid / analogs & derivatives*
  • Polyglutamic Acid / chemistry

Substances

  • Antineoplastic Agents, Phytogenic
  • Nanoconjugates
  • Peptides, Cyclic
  • cyclic (arginyl-glycyl-aspartyl-phenylalanyl-lysyl)
  • poly(gamma-glutamic acid)
  • Polyglutamic Acid
  • Phenylalanine
  • Camptothecin