文献：Ligand-modified homologous targeted cancer cell membrane biomimetic nanostructured lipid carriers for glioma therapy

文献链接：https://pubmed.ncbi.nlm.nih.gov/34668811/

作者：Mengyu Chen, Yuexin Cui, Wenyan Hao, Yueyue Fan, Jingqiu Zhang,Qianqian Liu, Mingrui Jiang, Yang Yang, Yingzi Wang & Chunsheng Gao

相关产品：DSPE-PEG2000-NHS（磷脂-聚乙二醇2000- N -羟基琥珀酰亚胺）

原文摘要：

The main treatment measure currently used for glioma treatment is chemotherapy; the biological barrier of solid tumors hinders the deep penetration of nanomedicines and limits anticancer therapy.Furthermore, the poor solubility of many chemotherapeutic drugs limits the efficacy of antitumor drugs. Therefore, improving the solubility of chemotherapeutic agents and drug delivery to tumor tissues through the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB) are major challenges in glioma treatment. Nanostructured lipid carriers (NLCs) have high drug loading capacity, high stability, and high in vivo safety; moreover, they can effectively improve the solubility of insoluble drugs.Therefore, in this study, we used solvent volatilization and ultrasonic melting methods to prepare dihydroartemisinin nanostructured lipid carrier (DHA-NLC). We further used the glioma C6 cancer cell (CC) membrane to encapsulate DHA-NLC owing to the homologous targeting mechanism of the CC membrane; however, the targeting ability of the CC membrane was weak. We accordingly used targeting ligands for modification, and developed a bionanostructured lipid carrier with BBB and BBTB penetration and tumor targeting abilities. The results showed that DHA-loaded NGR/CCNLC (asparagine–glycine–arginine, NGR) was highly targeted, could penetrate the BBB and BBTB, and showed good antitumor effects both in vitro and in vivo, which could effectively prolong the survival time of tumorbearing mice. Thus, the use of DHA-loaded NGR/CCNLC is an effective strategy for glioma treatment and has the potential to treat glioma.

DSPE - PEG2000 - NHS 是一种功能化的磷脂 - 聚乙二醇衍生物。其中 DSPE（1,2 - 二硬脂酰 - sn - 甘油 - 3 - 磷酸乙醇胺）是磷脂部分，具有两条长的脂肪酸链，这使分子的一端呈现疏水性。PEG2000（分子量为 2000 的聚乙二醇）是亲水性部分，它将 DSPE 和 NHS 连接起来，起到改善水溶性和生物相容性的作用。NHS 代表 N - 羟基琥珀酰亚胺（N - Hydroxysuccinimide），是一种活性官能团，其化学结构包含一个五元环状的琥珀酰亚胺结构，这种结构使得 NHS 能够与含有伯氨基（- NH₂）的化合物发生化学反应。该文献基于DSPE-PEG2000-NHS的性质，该文献产品的制备流程如下：

图：脂质体制备流程

靶向配体的合成：

采用活性酯法合成了靶向配体。以N-羟基硫代琥珀酰亚胺（NHS）为保护剂，DSPE-PEG2000-NHS中的酯键与NGR肽中的氨基在N、N0-二环己基碳二亚胺（DCC）催化下与DCC反应形成酰胺键，透析后对靶向配体进行冻干。通过1 H NMR和MALDI-TOF质谱证实了靶向配体的合成。

图：靶向配体的合成

结论：

该文献成功合成了基于DSPE-PEG2000-NHS的新型靶向配体负载dha的NGR/CCNLC。这种材料具有高载药能力、高稳定性、高体内安全性，并可有效提高不溶性化合物的溶解度。结果表明，负载dha的NGR/CCNLC（天冬酰胺-甘氨酸-精氨酸，NGR）具有高靶向性，可穿透血脑屏障和BBTB，在体内外均具有良好的抗tumour作用，可有效延长小鼠的生存时间。