Abstract P55: Targeted Delivery of Cdc42 Inhibitor CASIN to Colorectal Cancer Cells via Nucleolin-Binding Aptamer-Functionalized PLGA-PEG Nanoparticles
Altyn Zhuraliyeva, Sanazar Kadyr, Bauyrzhan Umbayev, Aislu Yermekova, Aigerim Makhambetova, Daulet Kaldybekov, Ellina Mun, Denis Bulanin, Sholpan AskarovaAbstract
Background:
Systemic inhibition of Cdc42 effectively suppresses the growth and metastasis of colorectal cancer but is associated with substantial side effects. To minimize these adverse effects, we have developed PLGA-PEG nanoparticles functionalized with DNA aptamers, enabling precise delivery of the Cdc42 inhibitor CASIN specifically to tumour cells via targeted binding to nucleolin, which is overexpressed in colorectal cancer.
Methods:
The nucleolin-targeting aptamer AS1411 (5′-FAM–GG TGG TGG TGG TTG TGG TGG TGG TGG–3′-NH2) was synthesized as a 28-nucleotide single-stranded DNA oligonucleotide with a 5′-fluorescein label and a 3′-terminal amino modification. PLGA-PEG-NHS nanoparticles were prepared by nanoprecipitation and subsequently conjugated with the AS1411 aptamer. The conjugation efficiency was confirmed by measuring DNA concentration, fluorescence microscopy, and Raman spectroscopy. The affinity and specificity of the aptamer-nanoparticle complexes toward nucleolin-expressing cancer cells were further confirmed by flow cytometry analysis.
Results:
PLGA-PEG-NHS nanoparticles conjugated with the AS1411 aptamer and loaded with CASIN had an average diameter of 129.3 ± 25 nm, a polydispersity index (PDI) of 0.259, and a zeta potential of –52.3 ± 3.6 mV. The encapsulation efficiency was 38.1%, and the drug loading capacity for CASIN was 7.35%. CASIN release from PLGA-PEG-AS1411 nanoparticles followed a biphasic pattern, with a rapid initial phase and continued gradual release over 48 hours. In vitro cytotoxicity assays demonstrated that CASIN-loaded, aptamer-modified nanoparticles significantly inhibited the proliferation of colorectal cancer cell lines (HT29, SW620, HCT116). NPs-AS1411-CASIN markedly reduced HT-29 cell migration, while NPs-AS1411 alone had minimal effect.
Conclusion:
In summary, this targeted nanoplatform shows promise for improving the selectivity and efficacy of colorectal cancer treatment. 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:
Altyn Zhuraliyeva, Sanazar Kadyr, Bauyrzhan Umbayev, Aislu Yermekova, Aigerim Makhambetova, Daulet Kaldybekov, Ellina Mun, Denis Bulanin, Sholpan Askarova. Targeted Delivery of Cdc42 Inhibitor CASIN to Colorectal Cancer Cells via Nucleolin-Binding Aptamer-Functionalized PLGA-PEG Nanoparticles [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 P55.