State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an, 710049, China.
State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an, 710049, China.
Carbohydr Polym. 2019 May 15;212:334-344. doi: 10.1016/j.carbpol.2019.02.045. Epub 2019 Feb 19.
Chemo-photothermal combination therapy is a promising strategy for cancer treatment. In this study, to achieve the combined photothermal-chemotherapy of breast cancer, a pH-sensitive oxidized hyaluronic acid-decorated dihydroxyphenyl/hydrazide bifunctionalized hydroxyethyl chitosan (DHHC)-gold nanorod (GNR) conjugate was developed. DHHC was synthesized by successive dihydroxyphenylation and hydrazidation of hydroxyethyl chitosan through carbodiimide reaction and click chemistry, respectively. The conjugate was obtained by chemically bonding DHHC onto GNR via Au-catechol bonds. Doxorubicin (DOX) was loaded onto the conjugate via an acid-labile hydrazone linkage with a drug loading content of 5.1%. DOX-loaded conjugate displayed good stability in neutral aqueous solutions and exhibited pH-responsive drug release and surface charge reversal behaviors. In vitro biological studies indicated that the conjugate could be effectively internalized by breast cancer MCF-7 cells and synergistic therapeutic effects were demonstrated, suggesting its great potential in combined photothermal-chemotherapy of breast cancer.
化疗-光热联合疗法是一种很有前途的癌症治疗策略。在这项研究中，为了实现乳腺癌的联合光热-化疗，开发了一种 pH 敏感的氧化透明质酸修饰的二羟基苯基/酰肼双功能化羟乙基壳聚糖（DHHC）-金纳米棒（GNR）缀合物。DHHC 通过碳二亚胺反应和点击化学分别将羟乙基壳聚糖二羟苯基化和酰肼化合成。通过 Au-儿茶酚键将 DHHC 化学结合到 GNR 上，得到了缀合物。阿霉素（DOX）通过酸不稳定的腙键负载到缀合物上，载药含量为 5.1%。载 DOX 的缀合物在中性水溶液中具有良好的稳定性，并表现出 pH 响应性药物释放和表面电荷反转行为。体外生物学研究表明，该缀合物可以被乳腺癌 MCF-7 细胞有效内化，并表现出协同治疗效果，表明其在乳腺癌联合光热-化疗中有很大的潜力。
