2024-12-18 作者：lkr 来源：文献：Lactoferrin- and RGD-comodified, temozolomide and vincristine-coloaded nanostructured lipid carriers for gliomatosis cerebri combination therapy
文献链接：https://pubmed.ncbi.nlm.nih.gov/29861635/
作者：Jicai Zhang ,Xiang Xiao ,Jianming Zhu ,Ziyun Gao ,Xianliang Lai ,Xingen Zhu ,Guohua Mao
相关产品：
DSPE-PEG2000-MAL 磷脂-聚乙二醇-马来酰亚胺
原文摘要：
Purpose: Glioblastoma multiforme (GBM) is the most common malignant brain tumor originating in the central nervous system in adults. Based on nanotechnology such as liposomes,polymeric nanoparticles, and lipid nanoparticles, recent research efforts have been aimed to target drugs to the brain.
Methods: In this study, lactoferrin- and arginine–glycine–aspartic acid (RGD) dual ligand-comodified, temozolomide and vincristine-coloaded nanostructured lipid carriers (L/RT/V-NLCs) were introduced for GBM combination therapy. The physicochemical properties of L/R-T/V-NLCs such as particle size, zeta potential, and encapsulated efficiency are measured.The drug release profile, cellular uptake, cytotoxicity, tissue distribution, and antitumor activity of L/R-T/V-NLCs are further investigated in vitro and in vivo.
Results: L/R-T/V-NLCs were stable with nanosize and high drug encapsulation efficiency.L/R-T/V-NLCs exhibited sustained-release behavior, high cellular uptake, high cytotoxicity and synergy effects, increased drug accumulation in the tumor tissue, and obvious tumor inhibition efficiency with low systemic toxicity.
Conclusion: L/R-T/V-NLCs could be a promising drug delivery system for glioblastoma chemotherapy.
DSPE-PEG2000-MAL是一种线性异双功能聚乙二醇化试剂，含有DSPE磷脂和马来酰亚胺官能团。马来酰亚胺官能团通常与巯基反应，形成稳定的共价键，可用于与其他分子或化合物中的巯基反应，实现共价结合。DSPEPEG2000-NH2是一种含有DSPE磷脂和胺基的线性异双功能聚乙二醇化试剂。胺基可用于生物结合靶向分子，如抗体、适体、蛋白质和肽。DSPE-PEG2000-MAL和DSPEPEG2000-NH2的应用较广，比如在纳米结构脂质载体制备中的应用。
图为：Lf-PEG-DSPE的化学结构
DSPE-PEG2000-MAL与DSPE-PEG2000-NH2在Lf-PEG-DSPE和RGD-PEG-DSPE中的合成应用：
乳铁蛋白-PEG-DSPE（通过将Lf结合到DSPE-PEG2000-MAL上的远端MAL官能团上合成的Lf-PEG-DSPE）合成。Lf首先用Traut试剂硫化。生成的硫醇化Lf加入当量的DSPE-PEG2000-MAL在室温下反应，形成硫醚与DSPE-PEG2000-MAL链N端的MAL官能团结合。将混合物离心搅拌，然后重新悬浮在PBS中。然后，冷冻干燥后获得Lf-PEG-DSPE，得到白色结晶粉末。 DSPE-PEG2000-NH2溶于DMSO中。加入RGD搅拌。反应完成后，用Milli-Q水连续透析溶液。冷冻干燥后得到RGD-PEG-DSPE。
图为：乳铁蛋白-peg-DSPE的合成途径。
结论：Lf-PEG-DSPE和RGD-PEG-DSPE的制备结论表明，这两种材料在药物输送和医学研究领域中具有应用前景。它们的制备过程需要严格控制反应条件和反应时间，以确保偶联物的纯度和生物活性。同时，这两种材料也展现出了良好的生物相容性、稳定性和靶向性，为药物输送系统的设计和优化提供了有力的支持。
