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.
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Authors | Sang Kyoon Kim, Michael B Foote, Leaf Huang |
Journal | Cancer letters
(Cancer Lett)
Vol. 334
Issue 2
Pg. 311-8
(Jul 01 2013)
ISSN: 1872-7980 [Electronic] Ireland |
PMID | 22796364
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2012 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Alexa 488 hydrazide
- Fluorescent Dyes
- Hydrazines
- Lipids
- Peptides
- ErbB Receptors
- Calcium Carbonate
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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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