Development of anti-SUV39H1 siRNA delivery systems for cancer therapy
Project no. 32149 · Status: Kapanmış · 2024
Summary
<p>Cancer is a broad group of diseases characterized by the uncontrolled growth of cells with abnormal proliferative properties. Gene silencing using siRNAs allows for the exploration of new treatment methods by targeting genes that trigger cancer formation. Nanotechnology's potential in genetic material delivery has been recently demonstrated in oligonucleotide drugs and COVID-19 vaccines.</p><p>siRNAs were designed using the iScore Designer web tool. Cationic LNPs were prepared by lyophilization-rehydration. siRNA was complexed with LNPs, and complex formation and nuclease stability were confirmed by gel retardation assay. LNPs and complexes were characterized by size and zeta potential. Cytotoxicity was evaluated on H1299, HCC827, and Calu1 cell lines. Cellular internalization was observed in Calu1 cells.</p><p>Two siRNA candidates with the highest iScore Designer scores were selected. LNPs with particle sizes of 62.4 - 87.4 nm and zeta potentials of +30.4 to +31.7 mV were obtained. LNP formulations formed complexes with siRNA at N/P ratios above 10. Complexes prepared at N/P ratios of 10, 15, and 20 had sizes below 100 nm. Increasing N/P ratio increased the complexes' anionic stress resistance. siRNA was protected from degradation above 60% in the presence of RNaseA. LNPs and complexes showed no toxicity in the tested cells. N/P 15 ratio provided optimal cellular uptake.</p><p>The developed LNP:siRNA complexes show good in vitro stability, biocompatibility, and cellular uptake. Further research on SUV39H1 silencing in lung cancer cells is warranted.</p>