Poster abstracts
Poster number 18 submitted by Archie Bhullar
Engineered Extracellular Vesicles for Combinatorial TNBC Therapy: SR-SIM-Guided Design Achieves Substantial Drug Dosage Reduction
Abhjeet Bhullar (b.Interdisciplinary Biophysics Graduate Program, The Ohio State University, Columbus, Ohio 43210, United States.), Kai Jin (a.Center for RNA Nanobiotechnology and Nanomedicine; College of Pharmacy and Comprehensive Cancer Center. The Ohio State University, Columbus, Ohio 43210, USA;), Peixuan Guo (a.Center for RNA Nanobiotechnology and Nanomedicine; College of Pharmacy and Comprehensive Cancer Center. The Ohio State University, Columbus, Ohio 43210, USA;), Daniel W. Binzel (a.Center for RNA Nanobiotechnology and Nanomedicine; College of Pharmacy and Comprehensive Cancer Center. The Ohio State University, Columbus, Ohio 43210, USA;), Dan Shu (a.Center for RNA Nanobiotechnology and Nanomedicine; College of Pharmacy and Comprehensive Cancer Center. The Ohio State University, Columbus, Ohio 43210, USA;)
Abstract:
Triple negative breast cancer is an aggressive subtype of breast cancer that has no therapeutic targets, relies on chemotherapeutics for treatment, and is in dire need of novel therapeutic approaches for improved patient outcomes. Extracellular vesicles serve as intercellular communicators and have been proposed as ideal drug delivery vehicles. Here, extracellular vesicles were engineered with RNA nanotechnology to develop highly effective tumor inhibitors. Utilizing Super Resolved-Structured Illumination Microscopy, extracellular vesicles were optimized for precise Survivin siRNA conjugated to chemotherapeutics loading and CD44 aptamer ligand decoration, thereby enhancing specificity towards triple negative breast cancer cells. Conventional treatments typically employ chemotherapy drugs Gemcitabine and Paclitaxel at dosages on the order of mg/kg respectively, per injection (IV) in mice. In contrast, engineered extracellular vesicles encapsulating these drugs saw functional tumor growth inhibition at significantly reduced concentrations: 2.2 µg/kg for Gemcitabine or 5.6 µg/kg for Paclitaxel, in combination with 21.5 µg/kg Survivin-siRNA in mice. This approach resulted in a substantial decrease of chemotherapeutic dose required, by orders of magnitude, compared to standard regimens. In vivo and in vitro evaluations in a triple negative breast cancer orthotopic xenograft mouse model demonstrated the efficacy of this reduced dosage strategy, indicating potential for decreased chemotherapy-associated toxicity.
Keywords: Extracellular Vesicles, RNA nanotechnology, Cancer therapy