Bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles as novel tumor targeting carriers

Nanotechnology. 2011 Apr 22;22(16):165101. doi: 10.1088/0957-4484/22/16/165101. Epub 2011 Mar 11.

Abstract

In this study, we have developed a novel carrier, micelle-type bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles (NPs), for the detection and treatment of pancreatic cancer. These NPs contained 4-arm-PEG as corona, and PLGA as core, the particle surface was conjugated with cyclo(arginine-glycine-aspartate) (cRGD) as ligand for in vivo tumor targeting. The hydrodynamic size of the NPs was determined to be 150-180 nm and the critical micellar concentration (CMC) was estimated to be 10.5 mg l( - 1). Our in vitro study shows that these NPs by themselves had negligible cytotoxicity to human pancreatic cancer (Panc-1) and human glioblastoma (U87) cell lines. Near infrared (NIR) microscopy and flow cytometry demonstrated that the cRGD conjugated PLGA-4-arm-PEG polymeric NPs were taken up more efficiently by U87MG glioma cells, over-expressing the α(v)β(3) integrin, when compared with the non-targeted NPs. Whole body imaging showed that the cRGD conjugated PLGA-4-arm-PEG branched polymeric NPs had the highest accumulation in the pancreatic tumor site of mice at 48 h post-injection. Physical, hematological, and pathological assays indicated low in vivo toxicity of this NP formulation. These studies on the ability of these bioconjugated PLGA-4-arm-PEG polymeric NPs suggest that the prepared polymeric NPs may serve as a promising platform for detection and targeted drug delivery for pancreatic cancer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line, Tumor
  • Drug Carriers / chemical synthesis*
  • Glioma / metabolism*
  • Humans
  • Male
  • Nanocapsules / chemistry*
  • Nanocapsules / ultrastructure
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacokinetics*
  • Polyethylene Glycols / chemistry*
  • Polyglactin 910 / chemistry*
  • Prostatic Neoplasms / metabolism*

Substances

  • Drug Carriers
  • Nanocapsules
  • Oligopeptides
  • poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer
  • Polyglactin 910
  • Polyethylene Glycols
  • arginyl-glycyl-aspartic acid