Abstract P39: Development and In Vitro Evaluation of PLGA-PEG Nanoparticles Encapsulating a Cdc42 Inhibitor for Targeted Colorectal Cancer Therapy

Abstract Background: CASIN, a Cdc42 inhibitor, can suppress the growth and metastasis of colorectal cancer cells but is limited by rapid clearance and poor bioavailability. In this study, we developed PLGA-PEG-COOH nanoparticles to encapsulate CASIN, aiming to improve its delivery and enable targeted inhibition of Cdc42 in colon cancer. Methods: We designed poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG-COOH) nanoparticles (NPs) encapsulating CASIN, a hydrophobic inhibitor targeting Cdc42. NPs were prepared by single emulsion self-assembly and thoroughly characterized for size, zeta-potential, encapsulation efficiency, loading capacity, and colloidal stability. Blood compatibility was tested via hemolytic assays. In vitro cytotoxicity was assessed by CCK8-based viability assay. Results: CASIN-PLGA-PEG-COOH nanoparticles were uniform, spherical, and averaged 86±1nm in diameter. Encapsulation efficiency was 66±5%, with a drug loading of 5±1%. CASIN release was sustained over 24 hours. These nanoparticles exhibited potent antiproliferative activity against colorectal cancer cell lines, including HT-29 (IC50 = 19.55 µM), SW620 (IC50 = 9.33 µM), and HCT116 (IC50 = 10.45 µM), at concentrations ranging from 0.025 to 0.375 mg/mL. Hemolysis tests confirmed excellent safety, with less than 1% hemolytic activity across all dosages. Conclusion: CASIN-PLGA-PEG-COOH nanoparticles demonstrated high encapsulation efficiency, controlled drug release, excellent hemocompatibility, and potent antitumor activity in vitro. These findings indicate that CASIN-loaded PLGA-PEG-COOH nanoparticles are a promising targeted therapy for colorectal cancer and warrant further evaluation in in vivo studies. This research has been funded by the Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan (Grant No. AP26100973) and Nazarbayev University, Collaborative Research Project (CRP) Grant No. 211123CRP1611. Citation Format: Bauyrzhan Umbayev, Sanazar Kadyr, Altyn Zhuraliyeva, Aislu Yermekova, Aigerim Makhambetova, Daulet Kaldybekov, Ellina Mun, Denis Bulanin, Sholpan Askarova. Development and In Vitro Evaluation of PLGA-PEG Nanoparticles Encapsulating a Cdc42 Inhibitor for Targeted Colorectal Cancer Therapy [abstract]. In: Proceedings of Frontiers in Cancer Science 2025; 2025 Nov 5-7; Singapore. Philadelphia (PA): AACR; Cancer Res 2026;86(13_Suppl):Abstract nr P39.