Diferenciação macrofágica induzida por nanopartículas de fosfatidilserina/7- cetocolesterol

Abstract

Cancer remains one of the leading causes of morbidity and mortality worldwide, characterized by uncontrolled cell growth and the establishment of an immunosuppressive tumor microenvironment (TME). Among the immune components within the TME, tumor-associated macrophages (TAMs) play a pivotal role by exhibiting either a pro-inflammatory (M1) or an anti-inflammatory (M2) phenotype. Therapeutic strategies have been developed to reprogram TAMs toward the M1 phenotype, thus enhancing antitumor immune responses. In this context, liposomal nanosystems containing phosphatidylserine (PS) and 7-ketocholesterol (7-KC) emerge as a promising approach. In this study, PS/7-KC liposomes were prepared using organic solvent evaporation followed by hydration. FTIR characterization confirmed the successful incorporation of both compounds. Zeta potential analysis demonstrated superior colloidal stability of the PS/7-KC formulation compared with PS alone after 90 days (–37.13 mV vs. – 47.40 mV; p = 0.0035). The particles exhibited an average size below 300 nm and an acceptable polydispersity index (< 0.5). Cell viability assessed by the MTT assay indicated low cytotoxicity at concentrations of 50 and 93 µg/mL, with significant cytotoxic effects observed only at 187.6 µg/mL. This pattern was consistent with the gene expression profile. At 50 and 93 µg/mL, there was a reduction in MCR expression (–3.43 and –4.51 log₂FC, respectively), whereas 187.6 µg/mL induced a robust increase in iNOS (+3.44 log₂FC; p < 0.01) and IL-12 (+1.66 log₂FC), along with a decrease in IL-10 (–2.52 log₂FC).These findings suggest that PS/7- KC liposomes can modulate macrophage polarization, promoting the M1 phenotype at higher concentrations while maintaining a favorable safety profile at intermediate concentrações. Overall, this nanoplatform demonstrates potential for antitumor immunotherapy strategies, warranting further in vivo studies and the development of controlled-release systems to optimize therapeutic outcomes.