Structurally distinct hybrid polymer/lipid nanoconstructs harboring a type-I ribotoxin as cellular imaging and glioblastoma-directed therapeutic vectors

Macromol Biosci. 2014 Dec;14(12):1696-711. doi: 10.1002/mabi.201400248. Epub 2014 Sep 2.

Abstract

A nanoformulation composed of a ribosome inactivating protein-curcin and a hybrid solid lipid nanovector has been devised against glioblastoma. The structurally distinct nanoparticles were highly compatible to human endothelial and neuronal cells. A sturdy drug release from the particles, recorded upto 72 h, was reflected in the time-dependent toxicity. Folate-targeted nanoparticles were specifically internalized by glioma, imparting superior toxicity and curbed an aggressively proliferating in vitro 3D cancer mass in addition to suppressing the anti-apoptotic survivin and cell matrix protein vinculin. Combined with the imaging potential of the encapsulated dye, the nanovector emanates as a multifunctional anti-cancer system.

Keywords: brain cancer; curcin; folate targeting; ribosome inactivating protein; solid lipid nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / metabolism
  • Brain Neoplasms* / pathology
  • Cell Line, Tumor
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacokinetics
  • Delayed-Action Preparations / pharmacology
  • Drug Screening Assays, Antitumor
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Glioblastoma* / drug therapy
  • Glioblastoma* / metabolism
  • Glioblastoma* / pathology
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism
  • Lipids* / chemistry
  • Lipids* / pharmacokinetics
  • Lipids* / pharmacology
  • Molecular Imaging*
  • Nanostructures / chemistry*
  • Neoplasm Proteins / metabolism
  • Neurons / metabolism
  • Neurons / pathology
  • Ribosome Inactivating Proteins, Type 1* / chemistry
  • Ribosome Inactivating Proteins, Type 1* / pharmacokinetics
  • Ribosome Inactivating Proteins, Type 1* / pharmacology
  • Survivin
  • Vinculin / metabolism

Substances

  • BIRC5 protein, human
  • Delayed-Action Preparations
  • Inhibitor of Apoptosis Proteins
  • Lipids
  • Neoplasm Proteins
  • Ribosome Inactivating Proteins, Type 1
  • Survivin
  • VCL protein, human
  • curcin protein, Jatropha curcas
  • Vinculin