Abstract B64: A Lys-Ala-Leu-Ala (KALA) repeated peptide modification in DNA nanoparticles of DOPE/CHEMS, follows GPCR mediated transgene expression in dendritic cell

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Abstract Cellular uptake process of cationic peptide modified liposome is still obscured in perspective of cell biology. The mechanisms responsible for the internalization of oligo arginine, oligo-lysine, TAT and other arginine or lysine enriched peptide have focused on macropinocytosis. No information was reported about the uptake process of repeated cationic arginine or lysine (hydrophilic moiety) followed by leucine or alanine (hydrophobic moiety) with lipid bilayer based DNA nanocargoes. Here we orchestrated the concept of repeated lys-ala-leu-ala (KALA) peptide modified DNA-protamine-lipid nanoparticle, proclaimed a promising transfection activity in dendritic cell, following GPCR mediated endocytosis. Chemical inhibitors studies of chlorpromazine, Fillipin, and Amiloride did not support the concept of macropinocytosis, clathrin mediated endocytosis and cavaeola mediated endocytosis. Cetirizine hydrochloride, a GPCR blocker shut down the KALA mediated transgene expression. Confocal studies showed no liposomal uptake in KALA modification rather than R8 modification, which implies to receptor mediated endocytosis and thereby transgene expression. Low concentration of KALA pretreatment allowed a R8 MEND (usually non-expressed) to that of the same expression of KALA MEND and vice versa of high concentration KALA pretreatment. In a nut-shell performance of KALA ensured an engulfment of GPCR based endocytosis as well as GPCR activation thereby, that outcomes a boom transgene expression in dendritic cell. Citation Format: Sharif Mohammad Shaheen, Hidetaka Akita, Hideyoshi Harashima. A Lys-Ala-Leu-Ala (KALA) repeated peptide modification in DNA nanoparticles of DOPE/CHEMS, follows GPCR mediated transgene expression in dendritic cell. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B64.