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The novel fusogenic peptides improve the delivery of therapeutics for ovarian cancer through their ability to enhance endosomal escape and delivery of bioactive therapeutics. Epithelial ovarian cancer is the 5th leading cancer among women, with a 49% five-year survival rate. Current treatment strategies for ovarian cancer include surgical removal, chemotherapy, and radiation; however, these treatments often prove ineffective or toxic to patients. Global News Wire expects the nanotechnology drug delivery market to have an 18.7% CAGR growth rate from 2022 to 2032. Current chemotherapies are limited due to the toxicity of therapeutic and resistance to treatment. Furthermore, there has been increased attention to reducing systemic effects and therapeutic concentration. This technology fills this gap by providing a means of delivery for therapeutics of RNA interference (RNAi), a mechanism used to silence genes responsible for cancer prognosis. While a promising strategy for treatment, RNAi cargo needs a delivery system to improve its bioavailability and delivery into cancer cells. Clemson University researchers have developed novel fusogenic peptides that have efficient delivery into ovarian cancer cells and enable the endosomal escape of therapeutic.
The fusogenic peptides are a delivery system designed to improve the intracellular delivery and endosomal escape of RNAi cargo to improve gene silencing for cancer treatment.
The peptides' design is composed of alternating residues of hydrophobic and hydrophilic amino acids, highlighted by repeating aspartic acid residues. Due to the inclusion of a cationic tail, these peptides have shown effective electrostatic complexation and protection of RNAi cargo. High biocompatibility and cellular internalization have been shown both in vitro and in vivo. These sequences have proven to enhance endosomal escape through the protonation of hydrophobic amino acids, which leads to a conformational change in a more acidic pH to disrupt the endosomal membrane. Upon release from the endosome, the siRNA is released into the cytoplasm of the cell, where it can be bioactive. Due to this enhanced delivery, gene silencing studies showed the system's efficacy in silencing the target oncogene. Therefore, these novel peptides demonstrate a highly efficient delivery system for RNAi therapeutic applications for cancer treatment.
Angela Alexander-Bryant, Timothy Samec
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