The specific delivery of oncogene therapeutics into cancer cells is a critical component towards the development of an effective cancer-targeting gene therapy approach. Towards this extent, we describe the synthesis, characterization and biological applications of cancer targeting peptides (CTPs), possessing the ability to specifically internalize anti-cancer agents within HepG2 liver cancer cells leading to potent anti-cancer activity. Based on the selection of the Glucose Regulated Protein 78 (GRP78) peptide ligand, Pep42, CTVALPGGYVRVC, various lengths of poly(L/D-arginine) sequences ranging from 3-15 residues were introduced within the CTP sequence to condense and internalize oncogene therapeutics directly into HepG2 cancer cells for potent anti-cancer effects. Towards this ultimate goal, CTPs were prepared in good yields (13-50%) and purities (>95%) by Solid Phase Peptide Synthesis (SPPS). Furthermore, the peptides were characterized by RP-HPLC, LCMS, and Circular Dichroism (CD) spectroscopy. With a better understanding of their structure and bio-physical properties, peptide biology was next assessed. Poly(arginine) derived CTPs maintained the ability to condense and internalize oncogene therapeutics within HepG2 cancer cells for potent anti-cancer effects. Considering the important utility of these peptides as tumor homing and drug delivery agents, this presentation will highlight our most recent accomplishments towards the development of a cancer-targeting gene therapy approach.

Poly(arginine) derived cancer-targeting peptides and their GRP78 targeting activity in HepG2 hepatoblastoma cells

248th National Meeting (2014)

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