Preparation of Liposomal Sanguinarine and Study of Its Cytotoxic Effects against Prostate Cancer Cells

Benzophenanthridine alkaloid sanguinarine from Macleaya macrocarpa shows antitumor and anti-angiogenic activity, among others. Some side effects of sanguinarine, which significantly limit the possibilities of its therapeutic use, are described. To increase the effectiveness of its therapeutic effect, sanguinarine was introduced into the pH-sensitive liposomes by remote loading using ammonium dihydrogen phosphate. pH-sensitive liposomes, appearing in the acidic environment of the tumor or endosomal compartment, release sanguinarine, which causes the death of tumor cells. The average diameter of the liposome particles measured by the method of dynamic light scattering was 112.6 +/- 1.8 nm; the zeta potential was -13.9 +/- 1.7 mV. The effectiveness of the inclusion of sanguinarine in liposomes was 89.54 +/- 2.13%. The dynamics of release of sanguinarine from the composition of a liposome preparation was studied, and the prolonged release pattern was demonstrated. The cytotoxic activity (CTA) of liposomal sanguinarine against prostate cancer cell lines LNCaP, DU 145, and PC-3 was studied. Liposomal sanguinarine exhibited dose-dependent CTA against cells of all the studied lines in the micromolar range of concentrations. The highest CTA of liposomal sanguinarine was seen against the hormone-sensitive LNCaP cells (IC50 2.86 mu M). For the hormone-independent cells of the DU 145 and PC-3 lines, the cytotoxic activity of liposomal sanguinarine was somewhat lower and amounted to 3.37 mu M and 3.63 mu M, respectively. A dose-dependent induction of apoptosis of LNCaP, DU 145, and PC-3 cells was also demonstrated. The liposomal sanguinarine with high efficiency induced apoptosis of both hormone-sensitive and hormone-independent cells. The liposomal sanguinarine at a concentration of 8 mu M induced apoptosis in 93.14% of LNCaP cells, 90.65% of DU 145 cells, and 98.12% of PC-3 cells. Thus, liposomal sanguinarine can be considered as a promising antitumor agent for the therapy of both hormone-sensitive and hormone-independent tumors.