Abstract—

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 μM). 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 μM and 3.63 μM, 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 μM 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.

中文翻译：

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脂质体血红素碱的制备及其对前列腺癌细胞的细胞毒作用研究

摘要-

Macleaya macrocarpa的苯并菲啶生物碱sanguinarine显示抗肿瘤和抗血管生成活性，等等。描述了血红碱的一些副作用，这些副作用大大限制了其治疗用途的可能性。为了增加其治疗效果的有效性，通过使用磷酸二氢铵的远程负载将血红碱碱引入到pH敏感的脂质体中。pH敏感的脂质体出现在肿瘤或内体区隔的酸性环境中，释放血红素碱，导致肿瘤细胞死亡。用动态光散射法测得的脂质体颗粒的平均直径为112.6±1.8nm。zeta电位为–13.9±1.7 mV。脂质体中包含血红素的有效率为89.54±2.13％。研究了血红素碱从脂质体制剂的组合物中释放的动力学，并且证明了延长的释放模式。研究了脂质体血红碱对前列腺癌细胞系LNCaP，DU 145和PC-3的细胞毒活性（CTA）。脂质体血红蛋白在微摩尔浓度范围内对所有研究品系的细胞均表现出剂量依赖性的CTA。观察到对激素敏感的LNCaP细胞（IC）脂质体血红碱的最高CTA₅₀ 2.86μM）。对于DU 145和PC-3系的非激素依赖性细胞，脂质体血红素碱的细胞毒活性略低，分别为3.37μM和3.63μM。还证实了剂量依赖性诱导LNCaP，DU 145和PC-3细胞凋亡。脂质体sanguinarine高效诱导激素敏感性和激素非依赖性细胞凋亡。浓度为8μM的脂质体血红素碱可诱导93.14％的LNCaP细胞，90.65％的DU 145细胞和98.12％的PC-3细胞凋亡。因此，脂质体血红碱可以被认为是用于治疗激素敏感性和激素非依赖性肿瘤的有希望的抗肿瘤剂。