Targeted delivery of EV peptide to tumor cell cytoplasm using lipid coated calcium carbonate nanoparticles.
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.
Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Sang Kyoon
SK
Kim
Michael B
MB
Foote
Leaf
L
Huang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D040761:Biomimetic Materials / Q000008:administration & dosage / Q000493:pharmacokinetics; D002119:Calcium Carbonate / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D006801:Humans; D006834:Hydrazines / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000008:administration & dosage*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage*; D010455:Peptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays
C417561:Alexa 488 hydrazide; D005456:Fluorescent Dyes; D006834:Hydrazines; D008055:Lipids; D010455:Peptides; D066246:ErbB Receptors; D002119:Calcium Carbonate