Fabrication of chitosan based nanocomposite with legumain sensitive properties using charge driven self-assembly strategy
Fabrication of chitosan based nanocomposite with legumain sensitive properties using charge driven self-assembly strategy
复制标题
使用电荷驱动自组装策略制备具有legumain敏感特性的基于壳聚糖的纳米复合材料
DOI：
10.1007/s10856-018-6149-y
复制
发表时间：
2018-09-01
影响因子：
3.7
通讯作者：
Lin, Sen
中科院分区：
文献类型：
--
作者：
Luo, Mengmeng;Li, Qing;Lin, Sen
摘要壳聚糖（CS）纳米粒（NPs）作为药物载体具有许多优点。它们通常在微乳液溶剂系统中制备，但这种途径可能在NP中留下显著水平的潜在有害有机溶剂残留物。在这项研究中，我们制备CS基纳米复合材料使用电荷驱动自组装在水性缓冲液中，从而避免使用有机溶剂。阿霉素（DOX）共价连接到带正电荷的CS与豆荚蛋白底物肽，以赋予靶向药物释放特性，因为豆荚蛋白往往是过表达的肿瘤或肿瘤相关的微环境。该前药溶液与带负电荷的甲氧基聚乙二醇-聚谷氨酸嵌段共聚物（PEG-PGA）在水性缓冲液中相互作用形成具有规则形态的纳米复合材料。通过向DOX前药溶液中加入不同浓度的PEG-PGA来调节这些NP的粒度和ζ电位。由于其对豆荚蛋白的敏感性，DOX纳米粒对脉络膜黑色素瘤细胞（Mum-2C）的细胞毒作用增强，对正常人角膜上皮细胞（HCEC）的细胞毒作用降低，表明其具有良好的靶向化疗药物的潜力。不使用微乳液溶剂体系和交联剂。
AbstractChitosan (CS) based nanoparticles (NPs) have several advantages in delivering drugs. They are usually prepared in a micro-emulsion solvent system but this route can leave significant levels of potentially harmful organic solvent residue in the NPs. In this study, we prepared CS based nanocomposites using charge driven self-assembly in an aqueous buffer, thus avoiding the use of organic solvents. Doxorubicin (DOX) was covalently attached to positive charged CS with a legumain substrate peptide to confer targeted drug release property, since legumain is often overexpressed in tumors or tumor associated micro environments. This DOX prodrug solution interacted with negative charged methoxyl poly (ethylene glycol)-block-poly (glutamic acid) copolymer (PEG-PGA) in an aqueous buffer forming nanocomposite with a regular morphology. The particle size and zeta potential of these NPs was regulated by the addition of different PEG–PGA concentrations into the DOX prodrug solution. Due to its potential for legumain triggered release, this DOX NP exhibited enhanced cytotoxicity against choroidal melanoma cell line (Mum-2C) and reduced cytotoxicity on normal human corneal epithelial cells (HCEC), suggesting a good potential for enhanced targeted delivery of chemotherapeutic agents.A chitosan based nanocomposite with legumain sensitive properties are rapidly controllable prepared in aqueous buffer by charge driven self-assembly strategy, without using micro-emulsion solvent system and cross-linking agents.