Comparative Thermodynamic and Chemical Characterization of PEGylated Dendrimers and Aptamer-Guided Niosomes for Oleuropein Delivery to Brain Metastases
نویسندگان
1 Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, Beirut, Lebanon- PO Box: 146404 Mazraa, Lebanon
2 Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, Beirut, Lebanon- PO Box: 146404 Mazraa, Lebanon
3 Department of Nutrition and Food Sciences, School of Arts and Sciences, Lebanese International University, Mouseitbeh, P.O. Box 146404, Mazraa, Beirut, Lebanon
4 College of Engineering and Technology, American University of the Middle East, Egaila 54200, Kuwait
5 Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, Beirut, Lebanon- PO Box: 146404 Mazraa, Lebanon
6 Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, Beirut, Lebanon- PO Box: 146404 Mazraa, Lebanon
7 Department of Nutrition and Food Sciences, School of Arts and Sciences, Lebanese International University, Mouseitbeh, P.O. Box 146404, Mazraa, Beirut, Lebanon
8 Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
doi
10.48309/chemm.2025.525728.1964چکیده
Developing chemically specific nanocarriers for targeted brain tumor therapy remains a clinical challenge. In this study, we present a comparative chemical and thermodynamic characterization of two oleuropein-based nanosystems: PEGylated PAMAM dendrimers and aptamer-functionalized niosomes (Apt-Nio-Ole), engineered for selective targeting of 4T1 breast cancer brain metastases using SRZ1 DNA aptamers.The PAMAM nanoplatform was constructed via stepwise conjugation of oleuropein, FITC, and aptamers through esterification, thiourea, and EDC/NHS coupling. Apt-Niosomes were prepared by thin-film hydration, followed by aptamer surface functionalization. Both systems were characterized via DLS, FE-SEM, and zeta potential analysis, while cytotoxicity and cellular uptake were assessed by MTT assay, flow cytometry, and fluorescence microscopy.Apt-Nio-Ole and Apt-PAMAM-Ole exhibited mean sizes of 93.73 ± 3.72 nm and 107.52 ± 6.81 nm, PDI values of 0.21 ± 0.05 and 0.31 ± 0.09, and zeta potentials of –17.88 ± 3.52 mV and –21.59 ± 4.26 mV, respectively. Entrapment efficiency and release rates were higher for Apt-Nio, whereas Apt-PAMAM offered enhanced chemical precision. Both systems showed high cytotoxicity against 4T1 cells (IC₅₀: 36.93 µg/mL vs. 46.5 µg/mL) and selective brain uptake in vivo.This study highlights PEGylated dendrimers as compact, cost-effective, and chemically tunable platforms for sustained and targeted drug release. Compared to vesicular systems, they offer superior imaging potential and surface modification flexibility—making them promising nanocarriers for clinical translation in brain-targeted drug delivery.
