文献：Development and characteristics of novel sonosensitive liposomes for vincristine bitartrate

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作者：Wen Lin, Xiaoxing Ma, Chaopei Zhou, Hong Yang, Yang Yang, Xiangyang Xie,Chunrong Yang & Cuiyan Han

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DSPE-mPEG2000 磷脂-甲氧基聚乙二醇2000

DSPE-PEG2000-Mal 磷脂-聚乙二醇2000-马来亚酰胺

原文摘要：The aim of drug delivery is to increase therapeutic efficacy. Externally triggered drug delivery systems enable site-specific and time-controlled drug release. To achieve this goal, our strategy was based on ultrasound-triggered release of an anticancer agent from sonosensitive liposomes (SL). To realize the ultrasound-triggered drug release, a lipophilic sonosensitizer, hematoporphyrin monomethyl ether (HMME) was incorporated into the lipid bilayer of liposomes. Once irradiated by the ultrasound in tumor tissues, the sonodynamic effect generated by HMME could lead to an efficient disruption of the lipid bilayer in the SL. After encapsulating vincristine bitartrate (VIN) as the model drug, the ultrasound-triggered lipid bilayer breakdown can trigger the instant release of VIN, enabling ultrasound-controlled chemotherapy with great specificity. In the in vitro and in vivo studies, by integrating tumor-specific targeting and stimuli-responsive controlled release into one system, VIN-loaded SL showed excellent antitumor efficacy. The SL could potentially produce viable clinical strategies for improved targeting efficiency of VIN for the treatment of related cancer. More importantly, this report provides an example of controlled release by means of a novel class of ultrasound triggering system.

DSPE - mPEG2000 是一种生物材料。其中，DSPE 使其能够在水溶液中自组装形成脂质体或胶束等纳米结构，这为化合物的包裹与运输提供了良好的载体基础。mPEG2000 是甲氧基聚乙二醇链段，分子量为 2000，其甲氧基端具有化学稳定性，而聚乙二醇链则呈现出亲水性，提高了整个材料的水溶性，还能有效防止蛋白质在材料表面的吸附与聚集，从而延长在体内的循环时间。这种材料可用于包裹各类小分子化合物、蛋白质化合物、核酸化合物等，提高化合物的稳定性、溶解性与生物利用度，并且有助于实现化合物的缓释与控释。 该文献的策略是基于超声触发的从超声敏感脂质体（SL）中释放一种化合物。为了实现超声触发的化合物释放，将亲脂性声增敏剂血卟啉单甲醚（HMME）加入到脂质体的脂质双分子层中。制备过程如下：

图：PBS中不同脂质体配方的体外释放VIN在孵育后，用超声波体外释放。

脂质体（NL）纳米载体的制备

用HSPC、胆固醇和DSPE-mPEG2000的脂质组成。将所有脂质混合物溶解在氯仿-甲醇的梨形烧瓶中，随后在真空下使用旋转蒸发器蒸发形成干膜。然后用柠檬酸缓冲溶液水合脂质膜。为了控制尺寸，脂质分散体通过使用微型挤出机，通过聚碳酸酯过滤器挤压。声敏感脂质体（SL）按照相同的程序制备，除了HMME以所需的摩尔比添加到这些脂质混合物中。同样，空白脂质体悬浮准备如上所述直接添加到柠檬酸缓冲溶液，获得化合物浓度，然后调整pH外部相7.5使用碳酸钠溶液和孵化。最后，将vin载脂质体（vin载NL或DRUG传递725vin载SL）用聚碳酸酯过滤器过滤消Poison ，并亚包装到无菌瓶中。

图：在PBS中体外释放装载VIN的SL和装载vin的NL

结论：tumor组织中被超声照射，HMME产生的声动力学效应可以导致DSPE-mPEG2000参与制备的SL中脂质双分子层的有效破坏。将双心酸长春新碱（VIN）作为模型化合物后，超声触发的脂质双层分解可触发VIN的即时释放，使超声控制具有较大的特异性。vin负载的SL显示出了良好的抗tumor效果。SL可以提高VIN相关cancer的靶向效率。