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 Dec 1;225:115206. doi: 10.1016/j.carbpol.2019.115206. Epub 2019 Aug 15.
Combination chemotherapy has attracted more and more attention in the field of anticancer treatment. Herein, a synergetic targeted combination chemotherapy of doxorubicin (DOX) and cisplatin in breast cancer was realized by HER2 antibody-decorated nanoparticles assembled from aldehyde hyaluronic acid (AHA) and hydroxyethyl chitosan (HECS). Cisplatin and DOX were successively conjugated onto AHA through chelation and Schiff's base reaction, respectively, forming DOX/cisplatin-loaded AHA inner core. The core was sequentially complexed with HECS and targeting HER2 antibody-conjugated AHA. The formed near-spherical nanoplatform had an average size of ∼160 nm and a zeta potential of -28 mV and displayed pH-responsive surface charge reversal and drug release behaviors. HER2 receptor-mediated active targeting significantly enhanced the cellular uptake of nanoplatform. Importantly, DOX and cisplatin exhibited a synergistic cell-killing effect in human breast cancer MCF-7 cells. These results clearly indicate that the novel nanoplatform is promising for synergistic combination chemotherapy of breast cancer.
联合化疗在抗肿瘤治疗领域越来越受到关注。在此，通过由醛基透明质酸（AHA）和羟乙基壳聚糖（HECS）组装而成的 HER2 抗体修饰的纳米粒子，实现了阿霉素（DOX）和顺铂在乳腺癌中的协同靶向联合化疗。顺铂和 DOX 分别通过螯合和席夫碱反应成功接枝到 AHA 上，形成负载 DOX/顺铂的 AHA 内核。该核依次与 HECS 和靶向 HER2 抗体修饰的 AHA 复合。形成的近球形纳米平台平均粒径约为 160nm，zeta 电位为-28mV，并表现出 pH 响应的表面电荷反转和药物释放行为。HER2 受体介导的主动靶向显著增强了纳米平台的细胞摄取。重要的是，DOX 和顺铂在人乳腺癌 MCF-7 细胞中表现出协同的细胞杀伤作用。这些结果清楚地表明，新型纳米平台有望用于乳腺癌的协同联合化疗。
