RESUMO
Glioblastoma (GBM) is the most prevalent malignant primary brain tumor and currently lacks an effective treatment. In this study, we utilized a microfluidic system to synthesize docosahexaenoic acid (DHA) liposomes for GBM therapy. DHA is an omega-3 (ω3) polyunsaturated fatty acid commonly found in human dietary consumption that has demonstrated potential in mitigating cancer development. The microfluidic device employed allowed for precise fine-tuning of the physicochemical properties of liposomes by adjusting the flow rate ratios, flow rates, and lipid concentrations. Three distinct-sized liposomes, ranging from 80 nm and 130 nm, were successfully internalized by GBM cells, and demonstrated the ability to reduce the viability of these cells. Furthermore, DHA liposomes proved significantly more efficient in triggering apoptotic pathways, through caspase-3-dependent mechanisms, in comparison to free DHA. Thus, the nanomedicine platform established in this study presents new opportunities in the development of liposome formulations incorporating ω3 fatty acids for cancer therapy.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Lipossomos/química , Ácidos Docosa-Hexaenoicos , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Microfluídica , Neoplasias Encefálicas/patologiaRESUMO
Glioblastoma (GBM) is a highly aggressive malignant brain tumor currently without an effective treatment. Inspired by the recent advances in cell membrane biomimetic nanocarriers and by the key role of macrophages in GBM pathology, we developed macrophage membrane liposomes (MML) for GBM targeting. For the first time, it was assessed the role of macrophage polarization states in the effectiveness of these drug delivery systems. Interestingly, we observed that MML derived from M2 macrophages (M2 MML) presents higher uptake and increased delivery of the anticarcinogenic drug doxorubicin compared to M1 macrophage-derived nanocarriers (M1 MML) and control liposomes (CL). Moreover, the lowest uptake by macrophages of MML reveals promising immune escaping properties. Notably, M2 macrophages unveiled a higher expression of integrin CD49d, a crucial protein involved in the bilateral communication of macrophages with tumor cells. Therefore, our findings suggest the potential of using M2 macrophage membranes to develop novel nanocarriers targeting GBM.