文献：

Construction of RGD peptide and shearable PEG co modified liposomes and evaluation of their in vitro anti-tumor effects

文献链接：

http://www.doc88.com/p-9582779446578.html

相关产品：

胆固醇-聚乙二醇-靶向肽 CHOL-PEG-RGD

原文摘要：

The aim of this project is to design and construct an intelligent drug delivery system, aiming to prolong the circulation time in the body, effectively combine active passive targeting, improve the effective uptake of target cells, thereby enhancing anti-tumor effects and achieving the goal of reducing toxicity and increasing efficiency in tumor treatment. Based on the unique physiological environment of tumors, this project designed and constructed an intelligent RGD (Arg Gly Asp tripeptide) and shear PEG co modified liposome using doxorubicin (DOX) as a model drug. The surface of this liposome is modified by two types of PEG chains, one is the short PEG2o0o chain (RGD-PEG200) with RGD terminal connection, and the other is the long PEGso0o chain containing disulfide bonds (S-S). In the blood circulation, the hydration layer formed by - S-S-PEGso0 can help prolong the retention time of liposomes, protect RGD targets, and improve passive targeting efficiency; At the tumor site, the long chain of S-S-PEGso00 can be cleaved under the action of reducing agents, such as exogenous cysteine (Cys), to expose RGD and actively target aB; Tumor cells overexpressing integrin receptors.

图为：胆固醇-聚乙二醇-靶向肽结构式

该文献介绍了通过高分子材料学、药剂学、药理学、分子生物学等手段的交叉应用，制备RGD与可剪切PEG共修饰阿霉素脂质体(RGD-PEG000-LP-S-S-PEGso00/DOX,RPKLSPSK/DOX)，并对其进行系统的体外研究。

图为：CHOL-PEG2000合成路线

图为：CHOL-PEG2000-RGD合成路线

CHOL-PEG2000-RGD 的合成方法：CHOL-PEG2000-CO0H(0.387g,0.15 mmol)和 NHS(0.026 g，0.23 mmol)溶于N，N-二甲基甲酰胺(DMF)2.5mL，向此溶液中滴加溶解有DMAP(0.055 g,0.22 mmol)和 DCC(0.046 g, 0.23 mmol)的 DMF 2 mL。搅拌 2h后,加入 RGD(0.111g,0.18 mmol)，室温、氮气保护条件下，轻微搅拌 24h。反应结束后，过滤除去 DCU沉淀，将产物置于透析袋(截留相对分子量为3500)中，在2L烧杯中蒸馏水透析48h(更换透析液8次)，冷冻干燥产物。

合成用于修饰脂质体的 RGD-PEGzo0o短链和带-S-S-的PEGsoo长链。通过四步反应逐步在 PEGz000的一端连接脂溶性的胆固醇(CHOL)基团，另一端连接具有主动靶向功能的RGD靶头，合成出CHOL-PEG2000-RGD。分别对合成中间产物和终产物进行薄层层析(TLC)以及核磁共振('HNMR)分析鉴定。PEGso00通过-S-S-与二硬脂酸磷脂酰乙醇胺(DSPE)连接形成DSPE-S-S-PEGso00，采用TLC和HNMR对其进行表征。采用后插入法将PEG链插入阿霉素脂质体表面，制备脂质体 RPKLSPSKIDOX，并考察其包封率、形态、粒径分布、Zeta电位、PEG体外可剪切性。

研究表明：所制备的智能化RGD与可剪切PEG共修饰阿霉素脂质体具有效结合主-被动靶向、提高靶细胞有效摄取，是一种具有潜力的靶向药物载体。