Comparative Thermodynamic and Chemical Characterization of PEGylated Dendrimers and Aptamer-Guided Niosomes for Oleuropein Delivery to Brain Metastases

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 ۴T۱ breast cancer brain metastases using SRZ۱ 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 ۹۳.۷۳ ± ۳.۷۲ nm and ۱۰۷.۵۲ ± ۶.۸۱ nm, PDI values of ۰.۲۱ ± ۰.۰۵ and ۰.۳۱ ± ۰.۰۹, and zeta potentials of –۱۷.۸۸ ± ۳.۵۲ mV and –۲۱.۵۹ ± ۴.۲۶ 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 ۴T۱ cells (IC₅₀: ۳۶.۹۳ µg/mL vs. ۴۶.۵ 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.

کلیدواژه ها:

SRZ۱Apt ، Oleuropein delivery ، Thermodynamic characterization ، Surface modification ، Brain metastatic Tumors ، Nanocarrier comparison