Premium
Novel approach for specific delivery of cytolytic peptides (melittin) to cancer cells using molecularly targeted perfluorocarbon nanoparticles
Author(s) -
Soman Neelesh R,
Lanza Gregory M,
Schlesinger Paul H,
Wickline Samuel A
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a31-a
Subject(s) - melittin , propidium iodide , peptide , chemistry , biochemistry , mastoparan , annexin , biophysics , microbiology and biotechnology , biology , cell , apoptosis , programmed cell death , receptor , g protein
Melittin is a amphipathic 26 amino acid alpha‐helical lytic peptide present in honey bee venom. Though the potential therapeutic utility of melittin has long been recognized, its lack of specificity, peptidase sensitivity, and the complexity of packaging the membrane lytic peptide has hampered its clinical application. We report the first stable incorporation of melittin into an outer lipid monolayer of a molecularly targeted perfluorocarbon nanoparticle (NP, size 250 nm) that serves as a delivery vehicle for the peptide. The insertion of melittin into NP lipid monolayer was confirmed and quantified by surface plasmon resonance and tryptophan fluorescence studies. Non‐targeted and a v b 3 ‐targeted melittin carrying NPs were ineffective at producing red blood cell lysis. Cell proliferation assay revealed that IC 50 for free melittin, non‐targeted melittin NPs, and targeted melittin NPs was 0.97 (±0.15) μM, 15.3 (±1.8) μM and 100.7 (±3.2) μM respectively. The controlled targeting to the integrin a v b 3 receptor provided selectivity in the manner of cell death with >90% apoptosis in C‐32 cells (by Annexin‐V FITC and Propidium Iodide staining). Stabilization of melittin in targeted nanoparticles until delivery by a contact‐facilitated mechanism offers a novel approach for utilizing lytic peptides as targeted anti‐cancer agents.