Synergistic chemotherapeutic effect of sorafenib-loaded pullulan-Dox conjugate nanoparticles against murine breast carcinoma
Synergistic chemotherapeutic effect of sorafenib-loaded pullulan-Dox conjugate nanoparticles against murine breast carcinoma
复制标题
索拉非尼负载支链淀粉-Dox缀合物纳米粒子对小鼠乳腺癌的协同化疗作用
DOI：
10.1039/c6nr09639e
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发表时间：
2017
期刊：
影响因子：
6.7
通讯作者：
Xingdong Zhang
中科院分区：
文献类型：
--
作者：
Junhui Sui;Yani Cui;Hanxu Cai;Shaoquan Bian;Zhiyi Xu;Ling Zhou;Yong Sun;Jie Liang;Yujiang Fan;Xingdong Zhang
制备了pH敏感的普鲁兰-阿霉素结合物-索拉非尼纳米粒(P-Dox/S)，作为协同联合给药系统治疗小鼠乳腺癌。该纳米粒通过化学偶联和物理负载的方法可以将Dox和索拉非尼以超高的载药量(65.34wt%)包埋在纳米粒中，但在生理条件下保持稳定，并随着pH的降低而逐渐释放。这些结合物可以有效地内化，并在体外明显抑制4T1细胞的生长。此外，体内动物模型的研究数据显示，协同组合P-Dox/S纳米粒在实体瘤组织部位大量蓄积，达到最大治疗效果；它们还显著抑制实体瘤的生长，甚至显著缩小实体瘤体积，与初始体积相比，不良反应明显减轻。抗肿瘤治疗效果明显优于相同浓度的游离药物或单一载药P-Dox纳米粒的联合化疗。这些有希望的结果表明，这些纳米粒子具有高效的协同化疗作用。P-Dox/S纳米粒联合化疗在克服肿瘤耐药和异质性方面具有重要的临床应用潜力。
pH-Sensitive pullulan-doxorubicin conjugates encapsulating sorafenib (P-Dox/S) nanoparticles were developed as a synergistic combinatorial delivery system against murine breast carcinoma. The nanoparticles can encapsulate Dox and sorafenib with ultra-high loading capacity (65.34 wt%) through chemical conjugation and physical loading, whereas can remain stable under physiological conditions and gradually release Dox and sorafenib with the decreasing pH. These conjugates can be effectively internalized and clearly suppress 4T1 cell growth in vitro. Furthermore, research data of in vivo animal models revealed that the synergistic combinatorial P-Dox/S nanoparticles heavily accumulated in solid tumor tissue sites to maximize therapeutic efficacy; they also significantly inhibited solid tumor growth, even remarkably reduced solid tumor volume in comparison to the initial volume, and obviously diminished adverse effects. The anti-tumor therapeutic effect obviously outperformed the delivery of combinational chemotherapy of free drugs or single drug-loaded P-Dox nanoparticles at the same concentration. These promising results indicate the high-efficiency synergistic chemotherapeutic effects of these nanoparticles. Combinational chemotherapy using P-Dox/S nanoparticles has important potential in the clinical treatment of malignancy for overcoming drug resistance and heterogeneity.