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Targeted delivery of EV peptide to tumor cell cytoplasm using lipid coated calcium carbonate nanoparticles.

Abstract
Intracellular-acting peptide drugs are effective for inhibiting cytoplasmic protein targets, yet face challenges with penetrating the cancer cell membrane. We have developed a lipid nanoparticle formulation that utilizes a pH-sensitive calcium carbonate complexation mechanism to enable the targeted delivery of the intracellular-acting therapeutic peptide EEEEpYFELV (EV) into lung cancer cells. Lipid-calcium-carbonate (LCC) nanoparticles were conjugated with anisamide, a targeting ligand for the sigma receptor which is expressed on lung cancer cells. LCC EV nanoparticle treatment provoked severe apoptotic effects in H460 non-small cell lung cancer cells in vitro. LCC NPs also mediated the specific delivery of Alexa-488-EV peptide to tumor tissue in vivo, provoking a high tumor growth retardation effect with minimal uptake by external organs and no toxic effects.
AuthorsSang Kyoon Kim, Michael B Foote, Leaf Huang
JournalCancer letters (Cancer Lett) Vol. 334 Issue 2 Pg. 311-8 (Jul 01 2013) ISSN: 1872-7980 [Electronic] Ireland
PMID22796364 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Alexa 488 hydrazide
  • Fluorescent Dyes
  • Hydrazines
  • Lipids
  • Peptides
  • ErbB Receptors
  • Calcium Carbonate
Topics
  • Animals
  • Apoptosis (drug effects)
  • Biomimetic Materials (administration & dosage, pharmacokinetics)
  • Calcium Carbonate (administration & dosage)
  • Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
  • Cell Line, Tumor
  • Cytoplasm (metabolism)
  • Drug Delivery Systems (methods)
  • ErbB Receptors (metabolism)
  • Female
  • Fluorescent Dyes (administration & dosage, analysis, pharmacokinetics)
  • Humans
  • Hydrazines (administration & dosage, analysis, pharmacokinetics)
  • Hydrogen-Ion Concentration
  • Lipids (administration & dosage)
  • Lung Neoplasms (drug therapy, pathology)
  • Mice
  • Mice, Nude
  • Nanoparticles (administration & dosage)
  • Peptides (administration & dosage, pharmacokinetics)
  • Random Allocation
  • Xenograft Model Antitumor Assays

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