Journal
CANCER LETTERS
Volume 334, Issue 2, Pages 311-318Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2012.07.011
Keywords
Therapeutic peptide; Apoptosis; Nanoparticle; Calcium carbonate
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Funding
- NIH [CA129835, CA149363]
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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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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