文献：Carrier-free highly drug-loaded biomimetic nanosuspensions encapsulated by cancer cell membrane based on homology and active targeting for the treatment of glioma

文献链接：https://qikan.cqvip.com/Qikan/Article/Detail?id=7106001467

作者：Yueyue Fan, Yuexin Cui, Wenyan Hao, Mengyu Chen,Qianqian Liu,Yuli Wang,Meiyan Yang, Zhiping Li,Wei Gong, Shiyong Song,Yang Yang, Chunsheng Gao

相关产品：DSPE-PEG2000-NHS 磷脂-聚乙二醇-活性脂

原文摘要：Nanosuspensions, as a new drug delivery system for insoluble drugs, are only composed of a drug and a small amount of stabilizer, which is dispersed in an aqueous solution with high drug-loading, small particle size, high dispersion, and large specific surface area. It can significantly improve the dissolution, bioavailability, and efficacy of insoluble drugs. In this study, paclitaxel nanosuspensions ((PTX)NS) were prepared by an ultrasonic precipitation method, with the characteristics of simple preparation and easy repetition. With the help of a homologous targeting mechanism, a kind of glioma C6 cancer cell membrane (CCM)-coated (PTX)NS was developed and modified with DWSW peptide to obtain DWSW-CCM-(PTX)NS with the functions of BBB penetration and tumor targeting. The results showed that the cancer cell membrane could effectively camouflage the nanosuspensions so that it was not cleared by the immune system and could cross the blood-brain-barrier (BBB) and selectively target tumor tissues. Cell uptake experiments and in vivo imaging confirmed that the uptake of DWSW-CCM-(PTX)NS by tumor cells and the distribution in intracranial gliomas increased. Cytotoxicity test and in vivo anti-glioma studies showed that DWSW-CCM-(PTX)NS could significantly inhibit the growth of glioma cells and significantly prolong the survival time of glioma-bearing mice. Finally, the cancer cell membrane coating endowed the nanosuspensions with the biological properties of homologous adhesion and immune escape. This study provides an integrated solution for improving the targeting of nanosuspensions and demonstrates the encouraging potential of biomimetic nanosuspensions applicable to tumor therapy.

DSPE-PEG2000-NHS 是一种具有特定结构和性能的化合物，在纳米药物递送系统中，DSPE-PEG2000-NHS 可以用于修饰纳米粒子的表面，提高纳米粒子的稳定性、生物相容性和靶向性。通过与药物分子或靶向配体进行共价连接，可以实现药物的控释和靶向递送，提高药物的效果，降低副作用。该文献介绍了仿生纳米悬浮液这种纳米材料，其设计和制备灵感来源于自然界中的生物结构和功能。这种悬浮液通常由纳米颗粒、表面活性剂以及可能的其他添加剂组成，具有物理、化学和生物性质，在多个领域展现出应用潜力，DSPE-PEG2000-NHS在仿生纳米悬浮液表征中具有重要的应用价值。

图为：用活性酯法合成靶向配体DSPE-PEG2000- DWSW，在DCC和NHS的存在下，多肽中的-nh2与DSPE-PEG2000-NHS中的活性酯发生反应。

DSPE-PEG2000-NHS在靶向配体合成中的应用：

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，在N，N‘-二环己基碳二酰亚胺（DCC）的催化下，DSPE-PEG2000-NHS中的酯键与DWSW肽中的氨基反应形成酰胺键。在透析后通过冻干获得目标配体。利用核磁共振（1 H-NMR）和MALDI-TOF质谱（MALDI-TOF MS）表征了靶向配体的合成。

DSPE-PEG2000-NHS在仿生纳米悬浮液表征中的应用：

使用动态光散射（DLS）或电子显微镜（如透射电子显微镜TEM、扫描电子显微镜SEM）等技术，测量纳米颗粒的粒径分布和观察其形貌。DSPE-PEG2000-NHS的修饰可能会影响纳米颗粒的粒径和形貌，因此需要对修饰前后的纳米颗粒进行表征，以评估修饰效果。通过测量纳米悬浮液在不同条件下的稳定性（如pH值、温度、离子强度等），评估DSPE-PEG2000-NHS对纳米颗粒稳定性的影响。DSPE-PEG2000-NHS能够形成一层亲水性的保护层，防止纳米颗粒在生物体内被吞噬或被免疫系统清除，从而提高其稳定性。如果DSPE-PEG2000-NHS与靶向配体（如抗体、肽等）共同修饰在纳米颗粒表面，则需要进行靶向性表征。通过细胞实验或动物实验，评估纳米颗粒对特定细胞或组织的靶向能力。例如，可以利用流式细胞术检测纳米颗粒与细胞的结合情况，或利用荧光显微镜观察纳米颗粒在动物体内的分布情况。

图为：DSPE-PEG2000-NHS的结构式

结论：DSPE-PEG2000-NHS（磷脂-聚乙二醇-活性脂）在仿生纳米悬浮液表征中的应用主要体现在其作为表面修饰剂，能够增强纳米颗粒的稳定性、生物相容性和靶向性。在动态光散射（DLS）技术中，DSPE-PEG2000-NHS 修饰的纳米悬浮液可以通过其表面的 PEG 链减少粒子间的相互作用，从而使 DLS 能够更准确地测量纳米粒子的流体动力学直径和粒度分布。这有助于了解纳米悬浮液的均匀性和稳定性，对于评估其在体内的分布和代谢具有重要意义。