Tumor-targeted carriers provide efficient delivery of chemotherapeutic agents to tumor. siRNA offers innovative therapeutics for cancer treatment; however, siRNA delivery is challenging due to short in vivo stability and negligible interaction with cell membrane. CGKRK is one of the well-known peptides which targets heparin sulfate receptor in the tumor cells. Therefore, it could be used for targeting chemotherapeutic agents to tumor. Cell-penetrating peptides containing alternate arginine and histidine amino acids (HR) are demonstrated to be efficient molecular transporters. We hypothesize that conjugation of fatty acylated CGKRK peptide with cell-penetrating peptides will provide efficient delivery and targeting of siRNA to the tumor cells. Several peptides with sequences (HR)4, [HR]4, C20-KH(HR)3, C20-KH(HR)3-CGKRK, [HR]4C20-CGKRK, CGKRK-C20 and (HR)5, where () indicates linear peptide and [ ] indicates cyclic peptide, were synthesized using Fmoc/tBu solid-phase peptide synthesis (SPPS), purified by preparative reverse-phase high-performance liquid chromatography (RP-HPLC), and analyzed by matrix-assisted laser desorption ionization time of flight ( MALDI-TOF) mass spectrometry. Peptides were tested for their binding affinity to siRNA using a standard SYBR Green II dye exclusion assay at different N/P ratios. The ratio required for 50% binding (termed BR50) of all the peptides studied were in the range of 0.06 to 0.20, and the maximum binding was observed with cyclic [HR]4 peptides (BR50 = 0.06). The HR peptides showed a highly significant binding and it can be inferred from the results that all modified peptides would completely bind the siRNA at N/P ratio of 1. Zeta potential, particle size, cytotoxicity, serum stability and gene silencing efficiency of peptide-siRNA complexes will be investigated and reported soon. Since the modified peptides being investigated have been shown to be effective molecular transporters, they are expected to efficiently deliver siRNA to the tumor cells.

Fatty acylated CGKRK conjugated cell-penetrating peptide for targeted delivery of siRNA in tumor

2019 Fall National Meeting

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