2025-02-14 作者：ZJ 来源：文献：Galactose Modified Liposomes for Effective Co-Delivery of Doxorubicin and Combretastatin A4.
文献链接：https://xueshu.baidu.com/usercenter/paper/show?paperid=1p4t0870kn4x0ma01a120mt05s359896&site=xueshu_se
作者：Bo Lian,Hua Wei,Ruiyan Pan,Jingui Sun,Bo Zhang,Jingliang Wu ,Xiujie Li, Guixiang Tian,
原文摘要：Background: Tumor angiogenesis plays a crucial role in tumor development, and recent efforts have been focused on combining proapoptotic and antiangiogenic activities to
enhance antitumor therapy.
Methods: In this study, galactose-modified liposomes (Gal-LPs) were prepared for codelivery of doxorubicin (DOX) and combretastatin A4 phosphate (CA4P). The co-cultured system composed of BEL-7402 and human umbilical vein endothelial cells (HUVEC) cells was established to effectively evaluate in vitro anti-tumor activity through cell viability and cell migration assay. Furthermore, both in vivo bio-distribution and anti-hepatoma effect of DOX&CA4P/Gal-LPs were investigated on H22 tumor cell-bearing mice.
Results: The results showed that DOX&CA4P/Gal-LPs were spherical with a mean particle size of 143 nm, and could readily be taken up by BEL-7402 cells. Compared with a mixture of free DOX and CA4P, the DOX&CA4P/Gal-LPs were more effective in inhibiting cell migration and exhibited stronger cytotoxicity against BEL-7402 cells alone or a co-cultured system. The in vitro studies showed that the co-cultured system was a more effective model to evaluate the anti-tumor activity of combination therapy. Moreover, DOX&CA4P/Gal-LPs exhibited a greater anti-hepatoma effect than other drug formulations, indicating that Gal-LPs could promote drug accumulation in the tumor region and improve the anti-tumor activity.
Conclusion: Gal-LPs co-loaded with chemotherapeutic and antiangiogenic drugs are a promising strategy for anti-hepatoma therapy.
DSPE-PEG-NHS是DSPE、PEG和N-羟基琥珀酰亚胺（NHS）的结合体。DSPE赋予了分子脂质亲和性，能很好地与细胞膜等脂质结构相互作用。PEG链段具有良好的亲水性，能增加整个分子在水溶液中的溶解性和稳定性，并且可有效减少在体内的非特异性吸附，延长其在体内的循环时间。NHS基团是一种活性很高的酯类，它可以与含有氨基的生物分子（如蛋白质、多肽）发生特异性的反应，形成稳定的酰胺键。DSPE-PEG-NHS可用于制备靶向化合物递送系统，通过与化合物或靶向配体连接，实现化合物的准确运输；也可用于生物分子的标记和修饰，在生物成像中发挥重要作用。该文献基于此制备半乳糖修饰脂质体（Gal-LPs）用于共传递阿霉素（DOX）和磷酸A4（CA4P）。过程如下：
图：DOX&CA4P/Gal-LPs的作用机制示意图
共载脂质体的制备
DSPE-PEG-Gal是通过DSPE-PEG-NHS与LA之间的两步反应合成的。采用薄膜蒸发法制备了24个Gal-LPs。L-α-磷脂酰胆碱、胆固醇和DSPEPEG-Gal以一定的质量比与氯仿一起混合。采用波长为633 nm的方法对Gal-LPs的粒径、ζ电位和聚色散指数（PdI）进行了表征。用透射电镜（TEM，HT7700，日本立）观察空白LPs和Gal-LPs的形貌。简单地说，将一滴Gal-LPs溶液放在一个铜网格上。干燥后，样品用2%的磷钨酸染色，然后在透射电镜下观察。
制备DOX&CA4P/Gal-LPs进行联合。
将L-α-磷脂酰胆碱、胆固醇和DOX的氯仿混合溶液蒸发，形成干脂膜。加入PBS中的CA4P溶液使脂质膜水化，然后对混合物溶液进行超声处理。同时，制备DOX&CA4P/LPs作为对照。对载药LPs的特性进行了测试。为了评价DOX&CA4P/Gal-LPs的稳定性，将样品分散在无血清的RPMI 1640培养基中。测量了粒径和ζ电势动态光散射。
图：(A) DOX&CA4P/LPs和(B) DOX&CA4P/Gal-LPs的粒径分布和透射电镜图像。
结论：DOX&CA4P/Gal-LPs呈球形，平均粒径为143 nm，很容易被BEL-7402细胞吸收。与游离DOX和CA4P混合物相比，DOX和CA4P/Gal-LPs在抑制细胞迁移方面更有效，对单独或BEL-7402细胞共培养系统表现出更强的细胞有害性。此外，DOX&CA4P/Gal-LPs比其他化合物制剂具有更大的作用，说明Gal-LPs可以促进化合物在tumor区域的积累，提高其抗tumor活性。
