Kim, Min Ju Kim, Hyosuk Gao, Xueliang Ryu, Ju Hee Yang, Yoosoo Kwon, Ick Chan Roberts, Thomas M. Kim, Sun Hwa 2024-01-19T14:04:14Z 2024-01-19T14:04:14Z 2022-01-10 2021-07 1226-086X https://pubs.kist.re.kr/handle/201004/116710 The phosphoinositide 3-kinase (PI3K) pathway playing an important role in cell proliferation, growth, and survival is one of the most frequently dysregulated pathways in cancer. However, PI3K inhibitors, used as a monotherapy, have shown limited therapeutic efficacies and high rates of side effects from acquired resistance to PI3K inhibition via feedback loop-mediated pathway reactivation and poor tolerability of small-molecule inhibitors. Here, we proposed a multi-targeting siRNA delivery system using polymerized siRNA-based nanoparticle formulations (Msi-NPs) as a PI3K-targeted anticancer therapy for simultaneous ablation of Rac1 and p110 beta-subunit of PI3K linked by a Rac-PI3K positive feedback loop. Msi-NPs could self-assemble from polymerized siRNAs targeting Rac1 and p110 beta together with thiolated glycol chitosan. The combinatory inhibition of Rac1 and p110 beta successfully inhibited the PI3K signaling pathway in PI3K tumor suppressor phosphatase and tensin homolog (PTEN) deficient prostate cancer cells, resulting in significant delays in cell proliferation and migration. The Msi-NP delivery system can provide an alternative therapeutic strategy to overcome the challenges in PI3K inhibitor monotherapy. (c) 2021 Published by Elsevier B.V. on behalf of The Korean Society of Industrial and Engineering Chemistry. English 한국공업화학회 Multi-targeting siRNA nanoparticles for simultaneous inhibition of PI3K and Rac1 in PTEN-deficient prostate cancer Article 10.1016/j.jiec.2021.04.024 1 Journal of Industrial and Engineering Chemistry, v.99, pp.196 - 203 Journal of Industrial and Engineering Chemistry 99 196 203 N scie scopus kci ART002742512 000655693700005 2-s2.0-85104582984 Chemistry, Multidisciplinary Engineering, Chemical Chemistry Engineering Article GLYCOL CHITOSAN NANOPARTICLES MESSENGER-RNA DELIVERY STABILITY COMPLEXES PROTEIN PI3K pathway RNAi Multi-targeting siRNA PTEN deficiency