文献：A Novel Class of Ultrasound-Triggerable Drug Delivery System for the Improved Treatment of Tumors

文献链接：https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00194

作者：Chaopei Zhou, Xiangyang Xie, Hong Yang, Shasha Zhang, Yinke Li, Changchun Kuang, Shiyao

Fu, Lin Cui, Meng Liang, Chunhong Gao, Yang Yang, Chunsheng Gao, and Chunrong Yang

相关产品：DSPE-PEG2000-NGR  磷脂-聚乙二醇2000-靶向肽NGR

https://www.ruixitech.com/product-details/dspe-peg-ngr.html

原文摘要：The controlled release of anticancer drugs at the tumor site is a central challenge in treating cancer. To achieve this goal, our strategy was based on tumor-specific targeting and ultrasound-triggered release of an anticancer agent from liposomal nanocarriers. To enhance the ultrasound-triggered drug release, we incorporated a lipophilic sonosensitizer, chlorin e6 (Ce6) ester, into the lipid bilayer of liposomes. Additionally, asparagine-glycine-arginine (NGR) that binds to CD13, which is overexpressed in tumor cells, was introduced into these liposomes. Under the navigation effects of the NGR, the novel ultrasound-triggerable NGR-modified liposomal nanocarrier (NGR/UT-L) accumulates in tumor sites. Once irradiated by ultrasound in tumor tissues, the sonodynamic effect produced by Ce6 could create more efficient disruptions of the lipid bilayer of the liposomal nanocarriers. After encapsulating doxorubicin (DOX) as the model drug, the ultrasound triggered lipid bilayer breakdown can spring the immediate release of DOX, making it possible for ultrasound-responsive chemotherapy with great selectivity. By combining tumor-specific targeting and stimuli-responsive controlled release into one system, NGR/UT-L demonstrated perfect antitumor effect. Moreover, this report provides an example of controlled-release by means of a novel class of ultrasound triggering system.

DSPE-PEG2000-NGR由三部分组成：DSPE（二硬脂酰基磷脂酰乙醇胺）、PEG（聚乙二醇）和NGR（一种靶向肽）。其中，DSPE具有亲脂性，PEG具有亲水性，而NGR则具有特异性靶向功能。NGR肽能够特异性地结合到tumor细胞表面的CD13受体上，这种受体在tumor新生vessel的内皮细胞上高度表达。因此，DSPE-PEG2000-NGR可以作为靶向分子，将化合物准确地输送到tumor组织，从而提高效果并减少副作用。DSPE-PEG2000-NGR在许多方面有应用，例如该文献在共轭物的合成与表征中，具体如下：

图为：DSPE-PEG2000-NGR的制备原理

DSPE-PEG2000-NGR在共轭物的合成与表征中的应用

NGR与DSPE-PEG2000-Mal混合在氯仿中包括三乙胺(5个乙基)，在室温下保持搅拌。反应物在透析袋，除去氯仿和过量的NGR。然后将溶液冻存，在低温下继续使用。通过测定得到的DSPE-PEG2000-NGR的分子量，对产品进行了确认。基质辅助激光解吸离子化飞行时间质谱(MALDI-TOF MS)

DSPE-PEG2000-NGR在功能共轭物合成中的应用

在研究中，通过DSPE-PEG2000-NGR的脂质插入，开发了一种肽修饰的超声触发脂质体(NGR/UT-L)。将半脱氨酸引入NGR肽的末端，其游离统基(-SH)基团可以通过硫醇-马来酰亚胺反应与DSPE-PEG2000马来酰亚胺反应，将肽和DSPE-PEG2000共轭。MALDI-TOFMS的结果表明NGR已成功共轭到DSPE-PEG2000上。

图为：DSPE-PEG2000-NGR的MALDI-TOF 质谱

结论：DSPE-PEG2000-NGR 在共轭物的合成与表征中发挥着重要作用。DSPE-PEG2000-NGR 可以通过化学反应与抗tumor化合物等活性分子进行共轭。例如，通过酰胺键形成、二硫键连接等方式，将化合物与 DSPE-PEG2000-NGR 结合，制备具有靶向性的化合物共轭物。这种共轭物能够提高化合物的靶向输送效率，降低对正常组织的副作用。DSPE-PEG2000-NGR 可以修饰脂质体、胶束等纳米载体。通过将其插入纳米载体的脂质双分子层中或与纳米载体表面的活性基团结合，赋予纳米载体tumor vessel 靶向性。这样的纳米载体共轭物能够实现化合物的靶向递送，提高效果。利用各种分析技术如核磁共振（NMR）、傅里叶变换红外光谱（FTIR）等，可以对 DSPE-PEG2000-NGR 及其共轭物的化学结构进行表征。确定共轭物中各组分的存在以及连接方式，验证共轭反应的成功进行。