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通过褐藻胶包覆的 pH 敏感脂质体靶向递送吉西他滨抑制胰腺癌的生长。

Growth inhibition of pancreatic cancer by targeted delivery of gemcitabine via fucoidan-coated pH-sensitive liposomes.

机构信息

Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

School of Life Sciences and Technology, China Pharmaceutical University, Nanjing, Jiangsu 211198, China.

出版信息

Int J Biol Macromol. 2024 Oct;277(Pt 3):134517. doi: 10.1016/j.ijbiomac.2024.134517. Epub 2024 Aug 5.

Abstract

Fucoidan-coated pH sensitive liposomes were designed for targeted delivery of gemcitabine (FU-GEM PSL) to treat pancreatic cancer (PC). FU-GEM PSL had a particle size of 175.3 ± 4.9 nm, zeta potential of -19.0 ± 3.7 mV, encapsulation efficiency (EE) of 74.05 ± 0.17 %, and drug loading (DL) of 21.27 ± 0.05 %. Cell experiments in vitro showed that FU-GEM PSL could increase the release of GEM and drug concentration, and could inhibit tumor cell proliferation by affecting the cell cycle. FU-GEM PSL entered cells through macropinocytosis and caveolin-mediated endocytosis to exert effects. Meanwhile, the expression of P-selectin was detected in human tissues, demonstrating the feasibility of targeting FU. Moreover, combined with animal experiments in vivo, FU-GEM PSL could inhibit the development of PC. Furthermore, anti-tumor experiments in vivo carried on BALB/c mice indicated that FU-GEM PSL had tumor suppression abilities and safety. Therefore, FU-GEM PSL is a promising formulation for PC therapy.

摘要

壳聚糖修饰的 pH 敏感脂质体被设计用于吉西他滨(FU-GEM PSL)的靶向递送来治疗胰腺癌(PC)。FU-GEM PSL 的粒径为 175.3 ± 4.9nm,zeta 电位为-19.0 ± 3.7mV,包封率(EE)为 74.05 ± 0.17%,载药量(DL)为 21.27 ± 0.05%。体外细胞实验表明,FU-GEM PSL 可以增加 GEM 的释放和药物浓度,并通过影响细胞周期抑制肿瘤细胞增殖。FU-GEM PSL 通过巨胞饮和网格蛋白介导的内吞作用进入细胞发挥作用。同时,在人组织中检测到 P-选择素的表达,证明了 FU 靶向的可行性。此外,结合体内动物实验,FU-GEM PSL 可以抑制 PC 的发展。此外,在 BALB/c 小鼠体内进行的抗肿瘤实验表明,FU-GEM PSL 具有肿瘤抑制能力和安全性。因此,FU-GEM PSL 是一种有前途的 PC 治疗制剂。

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