Nanopartículas lipídicas funcionalizadas com transferrina para a veiculação de cabazitaxel: desenvolvimento, caracterização físico-química e avaliação da eficácia em células de câncer de próstata

Abstract

Prostate cancer (PCa) is the fourth most common malignancy worldwide, and its treatment may show limited efficacy due to side effects and hypersensitivity. Cabazitaxel (CBZ) is an antineoplastic agent used in prostate cancer therapy; however, due to its low selectivity and high lipophilicity, chemotherapy often exhibits reduced effectiveness. In this context, transferrin-functionalized solid lipid nanoparticles (SLN) provide a targeted therapy directed to the transferrin receptor (TfR), which is overexpressed on the membrane of prostate cancer cells.This study aimed to develop transferrin-functionalized solid lipid nanoparticles loaded with cabazitaxel, characterize their physicochemical properties, and evaluate their in vitro efficacy in prostate cancer cell lines. Nanoparticles were prepared using a Box-Behnken factorial design and consisted of soybean phosphatidylcholine, glyceryl palmitostearate, and stearic acid. Transferrin was covalently bound to the DSPE-PEG-maleimide group present in the nanoparticle structure.The transferrin-functionalized SLNs showed a mean particle size of 139.76 nm ± 1.01, a polydispersity index (PDI) of 0.375 ± 0.003, a zeta potential of –34.76 mV ± 0.88, encapsulation efficiency (EE%) of 88% ± 12.5, and conjugation efficiency (CE%) of 71.61 ± 0.85%. Electron microscopy revealed spherical morphology. In electrophoresis, free transferrin showed a band at 80 kDa, while the functionalized nanoparticles did not, indicating protein binding to the nanoparticles. Circular dichroism confirmed the α-helical structure of transferrin, and fluorescence spectroscopy validated conjugation.The results highlight the relevance of nanostructured systems as a strategy to improve oncological therapy. High cell viability in L929 fibroblasts demonstrated the biocompatibility of the developed systems, while the marked reduction in viability in DU145 and PC3 prostate cancer lines confirmed the efficacy of lipidic encapsulation in inducing selective cytotoxicity. Although transferrin functionalization did not significantly enhance in vitro toxicity, the data indicate its potential as an active targeting vector, favoring cellular internalization in tumor cells overexpressing transferrin receptors. This selectivity represents an important advance in reducing systemic side effects and improving therapeutic efficacy.Overall, the findings presented here support the role of nanotechnology as a promising tool in the development of safer and more effective antitumor therapies.