文献：Preparation, therapeutic efficacy and intratumoral localization of targeted daunorubicin liposomes conjugating folate-PEG-CHEMS

作者：Subin Xiong a b, Bo Yu b, Jun Wu c, Hong Li b, Robert J. Lee

文献链接：https://www.sciencedirect.com/science/article/abs/pii/S0753332210001915

摘要：

Folate polyethylene glycol-cholesterol hemisuccinate (folate-PEG-CHEMS) is a novel folate ligand firstly synthesized by our group and demonstrated good stability and potential targeting results on KB cells in vitro. The current study further explored endocytosis mechanisms of liposomes via folate receptor on L1210JF cells and assessed targeted therapeutic efficacy of folate-PEG-CHEMS anchored liposomes loading daunorubicin (F-L-DNR) in vivo. Folate-PEG-CHEMS was synthesized by a modified method. The liposome properties, cell cytotoxicity, intracellular and intratumoral localization, and therapeutic efficacy on a murine tumor model bearing L1210JF cells were evaluated. High encapsulation efficiency (95.1% ± 1.5%) and appropriate particle size (76.0 ± 35.5 nm) and zeta potential (−12.83 ± 1.36 mV) were achieved for F-L-DNR. IC50 of F-L-DNR on L1210JF cells was 2–3-folds lower than that of non-targeted liposomal daunorubicin (L-DNR). Anticancer efficacy on L1210JF tumor model indicated that mice survival time of F-L-DNR group at doses of 5 mg/kg and 10 mg/kg was significantly longer than that of L-DNR or free DNR. Confocal fluorescence photographs of F-L-DNR indicated enhanced endocytosis of liposomes via folate receptor on L1210JF cells, prolonged retaining time in tumors and improved drug release in the tumor site at 24 h post intravenous injection of F-L-DNR. In conclusion, folate-PEG-CHEMS is an effective ligand for folate-targeted daunorubicin liposomes to achieve increased drug release in tumor and therapeutic efficacy.

本研究进一步探讨了脂质体通过叶酸受体在L1210JF细胞上的内吞机制，并评估了叶酸-PEG-CHEMS锚定的荷柔红霉素脂质体（F-L-DNR）在体内的靶向治疗效果。

采用改进的方法合成了叶酸-PEG-CHEMS。评估了脂质体特性、细胞毒性、细胞内和瘤内定位以及对携带L1210JF细胞的小鼠肿瘤模型的治疗效果。

F-L-DNR实现了高包封率（95.1%±1.5%）和适当的粒径（76.0±35.5 nm）和ζ电位（-12.83±1.36 mV）。F-L-DNR对L1210JF细胞的IC50比非靶向柔红霉素脂质体（L-DNR）低2-3倍。

F-L-DNR组在5mg/kg和10mg/kg剂量下的小鼠存活时间明显长于L-DNR或游离DNR。

F-L-DNR的共聚焦荧光照片表明，静脉注射F-L-DNR后24小时，脂质体通过L1210JF细胞上的叶酸受体增强了内吞作用，延长了在肿瘤中的保留时间，并改善了肿瘤部位的药物释放。

总之，叶酸-PEG-CHEMS是叶酸靶向柔红霉素脂质体的有效配体，可以增加肿瘤中的药物释放和治疗效果。

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