Huang Dan, Dai Haitao, Tang Keyu, Chen Bin, Zhu Hongzhang, Chen Dubo, Li Nan, Wang Yingzhao, Liu Chuwei, Huang Yonghui, Yang Jianyong, Zhang Chao, Lin Run, He Weiling
School of Biomedical Engineering, Sun Yat-Sen University, Shenzhen, Guangdong 518107, China.
Nanoscale. 2020 Oct 14;12(38):20002-20015. doi: 10.1039/d0nr04592f. Epub 2020 Sep 30.
The development of novel chemoembolization agents to improve the treatment efficacy of transarterial chemoembolization (TACE) against liver cancer remains an urgent need in clinical practice. Herein, a versatile composite microsphere with upper critical solution temperature (UCST) properties was prepared to encapsulate polydopamine coated superparamagnetic iron oxide nanoparticles (SPION@PDA) and doxorubicin for simultaneous chemoembolization and photothermal therapy. The microspheres were spherical with an average diameter of 100-300 μm and exhibited favorable drug loading capability as well as strong photothermal effect. Strikingly, synergistic enhancement of photothermal therapy and chemotherapy against chemoresistant liver cancer cells was achieved. The in vivo therapeutic efficacy and safety evaluations were performed using rabbit VX2 liver tumor models. It was revealed that a single treatment of the combination of TACE and photothermal procedure resulted in 87.5% complete response and 12.5% partial response for the microsphere group, whereas all tumors in the control group progressed rapidly. Contrast-enhanced computed tomography (CT) evaluation indicated that the tumor diameter decreased by 91.5% after treatment, while that in the control group increased by 86.5%. The pathology-proven tumor necrotic rate was 87.2%, which significantly surpassed that of 65.2% in the control group. Furthermore, serum liver enzyme and biochemical studies indicated a temporary liver injury which can be fully recovered. Our findings demonstrated that this microsphere may be advantageous for enhancing therapeutic efficacy of TACE against liver cancer.
开发新型化疗栓塞剂以提高经动脉化疗栓塞术（TACE）治疗肝癌的疗效在临床实践中仍然是迫切需求。在此，制备了一种具有上临界溶液温度（UCST）特性的多功能复合微球，用于包裹聚多巴胺包覆的超顺磁性氧化铁纳米颗粒（SPION@PDA）和阿霉素，以同时进行化疗栓塞和光热治疗。微球呈球形，平均直径为100 - 300μm，具有良好的载药能力以及强烈的光热效应。令人惊讶的是，实现了对化疗耐药肝癌细胞的光热治疗和化疗的协同增强。使用兔VX2肝肿瘤模型进行了体内治疗效果和安全性评估。结果显示，对于微球组，TACE与光热治疗联合单次治疗导致87.5%的完全缓解和12.5%的部分缓解，而对照组所有肿瘤均迅速进展。对比增强计算机断层扫描（CT）评估表明，治疗后肿瘤直径减小了91.5%，而对照组肿瘤直径增加了86.5%。病理证实的肿瘤坏死率为87.2%，显著超过对照组的65.2%。此外，血清肝酶和生化研究表明存在暂时的肝损伤，但可完全恢复。我们的研究结果表明，这种微球可能有利于提高TACE治疗肝癌的疗效。
