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pH and redox dual-sensitive polysaccharide nanoparticles for the efficient delivery of doxorubicin
Biomaterials Science ( IF 5.8 ) Pub Date : 2017-09-04 00:00:00 , DOI: 10.1039/c7bm00632b
Shengcai Yang 1, 2, 3, 4, 5 , Zhaohui Tang 3, 4, 5, 6, 7 , Dawei Zhang 3, 4, 5, 6, 7 , Mingxiao Deng 1, 4, 8, 9 , Xuesi Chen 1, 2, 3, 4, 5
Affiliation  

A pH and redox dual-sensitive biodegradable polysaccharide, succinic acid-decorated dextran-g-phenylalanine ethyl ester-g-cysteine ethyl ester (Dex-SA-L-Phe-L-Cys), was synthesized to load doxorubicin hydrochloride (DOX·HCl). The DOX-loaded nanoparticles, which were prepared in aqueous solution and free of organic solvent, could spontaneously self-assemble into uniform sizes. When loading DOX·HCl, mercapto Dex-SA-L-Phe-L-Cys was oxidized into a crosslinked disulfide linkage to form pH and redox dual-sensitive nanoparticles (DOX-S-NPs). The amphiphilic polymer loaded DOX·HCl into the core through electrostatic and hydrophobic interactions, meanwhile the crosslinked disulfide bond could stabilize the drug loaded nanoparticles. As a control with similar polymer structure, succinic acid decorated dextran-g-phenylalanine ethyl ester (Dex-SA-L-Phe) was prepared to obtain pH-sensitive DOX-loaded micelles (DOX-N-NPs). The controlled pH and redox-dependent release profiles of the DOX-S-NPs in vitro were certified in different releasing mediums. Furthermore, the cellular uptake of the DOX-S-NPs was comparable with that of free DOX·HCl, determined by confocal laser scanning microscopy (CLSM) and flow cytometry. Cytotoxicity assay in vitro showed that the DOX-S-NPs and free DOX·HCl were similar in inhibiting the proliferation of non-small cell lung carcinoma A549 and breast cancer MCF-7 cell lines. DOX-S-NPs displayed similar antitumor efficiency compared with free DOX·HCl, but lower toxicity by body weight. These dual-sensitive DOX-S-NPs provide a useful strategy for anti-tumor therapy.

中文翻译:

pH和氧化还原双重敏感多糖纳米颗粒可有效递送阿霉素

合成了pH和氧化还原双敏感的生物可降解多糖,琥珀酸修饰的葡聚糖-g-苯丙氨酸乙酯-g-半胱氨酸乙酯(Dex-SA- L -Phe- L -Cys),以负载盐酸阿霉素(DOX· HCl)。在水溶液中制备的不含有机溶剂的DOX负载纳米颗粒可以自发自组装成均匀的尺寸。装载DOX·HCl时,巯基Dex-SA- L -Phe- L-Cys被氧化成交联的二硫键,形成pH和氧化还原双敏感纳米颗粒(DOX-S-NPs)。两亲性聚合物通过静电和疏水相互作用将DOX·HCl负载到核中,同时交联的二硫键可以稳定载药的纳米颗粒。与类似的聚合物结构,琥珀酸控制饰葡聚糖-苯丙氨酸乙酯(DEX-SA-大号-Phe)制备,得到pH敏感装载DOX的胶束(DOX-N-NPS)。体外DOX-S-NPs的受控pH和氧化还原依赖性释放曲线在不同的释放介质中进行了认证。此外,通过共聚焦激光扫描显微镜(CLSM)和流式细胞仪测定,DOX-S-NPs的细胞吸收与游离DOX·HCl相当。体外细胞毒性试验表明,DOX-S-NPs和游离DOX·HCl在抑制非小细胞肺癌A549和乳腺癌MCF-7细胞系的增殖中具有相似的作用。与游离DOX·HCl相比,DOX-S-NPs具有相似的抗肿瘤功效,但按体重的毒性较低。这些双重敏感的DOX-S-NP为抗肿瘤治疗提供了有用的策略。
更新日期:2017-09-15
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