Development of BMX siRNA Lipid Nanoparticles Using Novel Ionizable, and Cleavable Lipids Discovered through AI and Experimentation for Cancer Therapy.
Author : Abdulaziz Nasser Alasmari
Abstract :Purpose: This study aims to design, synthesize, and characterize novel ionizable and cleavable lipids that are derived from the γ-T3 isomer of vitamin E. The designed two lipids are used in the lipid nanoparticles (LNPs) structure to enhance BMX siRNA delivery for protein silencing and act as active anticancer agents. Methods: In this work, the delivery system used is composed of negatively charged siRNA encapsulated into a multi-component structure that contains DOPE, 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), Cholesterol, and Phosphatidylcholine. To further enhance the activity of the BMX siRNA lipid nanoparticle compositions, two novel lipids, a cleavable PEGylated lipid and an ionizable cationic lipid, were synthesized and characterized by our team (Abu-Fayyad and Nazzal 2017) and then added to the formulation. Results: The designed and optimized novel BMX siRNA LNPs were physicochemically characterized and exhibited the desired characteristics. Furthermore, AI-based tools were used to predict potential interactions between the novel, ionizable lipid and the BMX siRNA, yielding promising forecasted results. The optimized BMX siRNA LNPs exhibited a preferred particle size and zeta potential values of 151 nm and 30 mV, respectively. The novel and optimized BMX siRNA LNPs showed acid-based release of the active therapeutic agent. An in-vitro cell culture study against prostate cancer cell lines further supported the idea that these novel LNPs would be potent and more active compared to control formulas. Conclusion: In summary, the current work showed a successful development and characterization of anticancer novel LNPs for targeting the novel and emerging target BMX as a second option of therapeutics development, after the initial reported work our group published recently on small molecule therapeutics development (Elsanhoury, Alasmari et al. 2023).
Keywords :Novel Vitamin E-Derived Lipids for Enhanced BMX siRNA Nanoparticle Cancer Therapy
Conference Name :International Conference on Clinical Pharmacy and Personalized Medicine (ICCPPM-25)
Conference Place Miami, USA
Conference Date 22nd Aug 2025
