Construction of folate-conjugated epirubicin liposomes for enhancing the cellular uptake and the co-localization with nuclei of invasive breast cancer cells

叶酸偶联表阿霉素脂质体的构建及其增强侵袭性乳腺癌细胞摄取和核定位效应的研究（英文）

Drug resistance of anthracycline in the invasive cancer is associated with the lowered cellular drug uptake and diminished co-localization of drug with nuclei. In the present study, we aimed to construct the folate-conjugated epirubicin liposomes by incorporating a synthesized folate-lipid derivative; and to assess the effects on cellular drug uptake, co-localization of drug with nuclei and efficacy in treatment of invasive breast cancer cells. The studies were performed on invasive human breast cancer cells. The folate-PEG2ooo-DSPE conjugate was synthesized, and the constructed folate-conjugated epirubicin liposomes were approximately 1 O0 nm in size. The in vitro studies demonstrated that the folate-conjugated epirubicin liposomes had the strongest cellular drug uptake and co-localization with nuclei of the invasive breast cancer cells. Besides, the liposomes displayed the most significant efficacy in killing the invasive cancer cells, in preventing their invasive potential, and in penetrating ability into breast cancer spheroid as well. In conclusion, the constructed folate-conjugated epirubicin liposomes were able to enhance the efficacy in treatment of invasive breast cancer by improving the cellular drug uptake and increasing the co-localization with nuclei, hence offering a new strategy for potentially eradicating the invasive breast cancer cells.

侵袭性乳腺癌对蒽环类药物表现出较强的抗药性,其原因与药物在癌细胞摄取减少、难以定位到细胞核相关。本研究旨在构建一种叶酸偶联表阿霉素脂质体,将新合成的叶酸–脂质衍生物修饰到脂质体上,以增强侵袭性乳腺癌细胞的药物摄取和细胞核共定位,从而达到清除癌细胞的效果。研究以侵袭性乳腺癌细胞MDA-MB-435S细胞为模型展开。本研究合成了新型叶酸-PEG_(2000)-DSPE共聚物,并构建了叶酸偶联表阿霉素脂质体,载药脂质体的平均粒径约为100 nm;体外试验表明,同对照组相比,叶酸偶联表阿霉素脂质体表现出最强的癌细胞摄取效应和癌细胞核定位效应;并且,构建的载药脂质体表现最强的杀伤侵袭性乳腺癌细胞效应、抑制侵袭性乳腺癌细胞损伤修复效应和对体外乳腺癌肿瘤球最强的穿透效应。因此,构建的叶酸偶联表阿霉素脂质体可通过增加侵袭性乳腺癌细胞摄取及细胞核共定位效应,达到杀伤侵袭性乳腺癌细胞的效果。通过后续开发,叶酸偶联表阿霉素脂质体可望成为一种治疗侵袭性乳腺癌的新型制剂,该研究也为侵袭性乳腺癌治疗提供了潜在的新策略。