Han Xiao, Xu Xiaoquan, Tang Yuxia, Zhu Feipeng, Tian Ying, Liu Wei, He Doudou, Lu Guangming, Gu Yunfei, Wang Shouju
The First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Department of Radiology, Jinling Hospital, Nanjing Medical University, Nanjing, China.
Front Mol Biosci. 2020 Dec 3;7:610084. doi: 10.3389/fmolb.2020.610084. eCollection 2020.
Anaplastic thyroid cancer (ATC) is a highly aggressive and the most lethal type of thyroid cancer. The standard-of-care for unresectable ATC is radiotherapy and chemotherapy, usually based on doxorubicin (Dox). However, most patients develop resistance shortly after treatment. To overcome the drug resistance, we synthesized the mesoporous organosilica nanoparticles (MONPs) loaded with Dox and stabilized the nanocomposites by bovine serum albumin (BSA). The surface area and pore volume of MONPs were 612.653 m/g and 0.589 cm/g. The loading capacity of Dox-MONPs reached 47.02%. Compared to Dox-MONPs and free Dox, BSA-Dox-MONPs had more durable tumor-killing power on both drug-sensitive cell line HTh74 and drug-resistant cell line HTh74R. The cellular uptake of BSA-Dox-MONPs was 28.14 and 65.53% higher than that of Dox-MONP in HTh74 and HTh74R. Furthermore, the BSA coating decreased the efflux rate of nanocomposites in HTh74 (from 38.95 to 33.05%) and HTh74R (from 43.03 to 32.07%). In summary, BSA-Dox-MONPs reversed the chemotherapy resistance of ATC cells via increased drug uptake and inhibited drug efflux, offering a promising platform for the treatment of chemo-resistant ATC.
间变性甲状腺癌（ATC）是一种侵袭性很强且致死率最高的甲状腺癌类型。不可切除的ATC的标准治疗方法是放疗和化疗，通常以阿霉素（Dox）为基础。然而，大多数患者在治疗后不久就会产生耐药性。为了克服耐药性，我们合成了负载阿霉素的介孔有机硅纳米颗粒（MONPs），并用牛血清白蛋白（BSA）稳定了纳米复合材料。MONPs的比表面积和孔体积分别为612.653 m/g和0.589 cm/g。阿霉素-MONPs的负载量达到47.02%。与阿霉素-MONPs和游离阿霉素相比，BSA-阿霉素-MONPs对药物敏感细胞系HTh74和耐药细胞系HTh74R均具有更持久的肿瘤杀伤能力。在HTh74和HTh74R中，BSA-阿霉素-MONPs的细胞摄取量分别比阿霉素-MONP高28.14%和65.53%。此外，BSA包衣降低了纳米复合材料在HTh74（从38.95%降至33.05%）和HTh74R（从43.03%降至32.07%）中的外排率。总之，BSA-阿霉素-MONPs通过增加药物摄取和抑制药物外排逆转了ATC细胞的化疗耐药性，为化疗耐药性ATC的治疗提供了一个有前景的平台。
