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), were 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 size. When loading DOX•HCl, mercapto Dex-SA-L-Phe-L-Cys was oxidized into crosslinked disulfide linkage to form pH and redox dual-sensitive nanoparticles (DOX-S-NPs). The amphiphilic polymer loaded DOX•HCl into 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 DOX-S-NPs in vitro were certified in different releasing mediums. Furthermore, the cellular uptake of DOX-S-NPs were comparable with 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 in body weight. These dual-sensitive DOX-S-NPs provided a useful strategy for anti-tumor therapy.

中文翻译：

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pH和氧化还原双重敏感多糖纳米颗粒可有效递送阿霉素

pH和氧化还原双敏感生物可降解多糖，琥珀酸修饰的葡聚糖-g-苯丙氨酸乙酯-g合成了-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负载纳米粒子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药物负载的纳米颗粒。与类似的聚合物结构的控制，琥珀酸葡聚糖装饰克制备了-苯丙氨酸乙酯（Dex-SA-L-Phe），以获得pH敏感的装载DOX的胶束（DOX-N-NPs）。在不同的释放介质中证明了DOX-S-NPs的受控pH和氧化还原依赖性释放曲线。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，但对体重的毒性较低。这些双重敏感的DOX-S-NPs为抗肿瘤治疗提供了有用的策略。