engleski

Ascorbyl-palmitate incorporated solid lipid nanoparticles for targeting cancer stem cells

Targeting cancer stem cells (CSC) is significant because they are considered responsible for metastasis formation and relapse after conventional chemotherapy. Ascorbic acid (AA) has been thoroughly investigated as an anticancer agent due to its specific cytotoxic effect on CSC. Because of the instability of ascorbic acid, its derivatives are often used to improve delivery bioavailability. As an alternative, we have used the ascorbyl palmitate (AP), a lipophilic derivative of AA. But for utilization in aqueous environments, AP has to be incorporated in carriers, due to its lipophilic nature. For that purpose, we have synthesized solid lipid nanoparticles with AP (SLN-AP) using the microemulsion technique (water in oil). They were analyzed by measuring their size and polydispersity by DLS and zeta-potential by ELS. Also, for evaluation of morphology, they were visualized on TEM. Cellular uptake of SLNs containing fluorescent dye coumarin-6 was analyzed on HEK 293, U2OS and patient-derived sarcoma CSC by fluorescent microscope during 48h. The effect of SLN-AP on the viability of patient-derived sarcoma CSC (n=5) was determined by the MTT test. DLS analysis of SLN-AP showed that nanoparticles have a diameter of 414 nm, the zeta potential of 0 mV and polydispersity of 0, 228. TEM revealed round morphology and confirmed the size of nanoparticles. SLN containing coumarin-6 are successfully and gradually uptaken by cell lines HEK293, U2OS and patient-derived sarcoma CSC. However, the high exosome/vesicle activity was noticed on the CSC membranes suggesting possible efflux of SLN. Viability assays show that sarcoma CSC have diverse sensitivity to SLN-AP treatment and they are sensitive to up to 33 µM concentration of ascorbate delivered by SLN-AP. In conclusion, we have successfully synthesized and characterized ascorbyl palmitate-incorporated solid lipid nanoparticles. The SLN-AP gradually enter the cells and affect the viability of sarcoma CSC. Therefore, our research confirms the potential of SLN-AP for targeting sarcoma CSC.

solid lipid nanoparticles ; cancer stem cells ; ascorbate

nije evidentirano