The use of hollow mesoporous silica nanospheres to encapsulate bortezomib and improve efficacy for non-small cell lung cancer therapy
The use of hollow mesoporous silica nanospheres to encapsulate bortezomib and improve efficacy for non-small cell lung cancer therapy
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使用中空介孔二氧化硅纳米球封装硼替佐米并提高非小细胞肺癌治疗的疗效
DOI：
10.1016/j.biomaterials.2013.09.098
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发表时间：
2014-01-01
期刊：
影响因子：
14
通讯作者：
Hu, Ronggui
中科院分区：
文献类型：
--
作者：
Shen, Jia;Song, Guosheng;Hu, Ronggui
硼替佐米（BTZ）是首个获批用于治疗多种人类恶性肿瘤的临床蛋白酶体抑制剂。然而，BTZ水溶性差、稳定性低，且肿瘤耐药性的出现，严重限制了其治疗效果。在此，我们报道了中空介孔二氧化硅纳米球（HMSNs）在包裹BTZ用于药物递送方面的应用。在对人非小细胞肺癌H1299细胞的体外细胞活力测定中，HMSNs - BTZ在48小时处理后的半数最大抑制浓度（IC50）是游离BTZ的42%。体内抑瘤实验进一步表明，HMSNs - BTZ（0.3毫克/千克）的抗肿瘤活性约为游离BTZ的1.5倍。此外，我们发现，HMSNs - BTZ能更有效地诱导细胞周期停滞和细胞凋亡，同时促进半胱天冬酶3的激活和自噬，这可能是其抗肿瘤疗效提高的机制。最后，在野生型p53信号通路存在的情况下，HMSNs - BTZ的抑瘤效果得到增强，这表明联合p53基因治疗和基于BTZ的化疗可能会提高临床疗效。因此，基于HMSNs的纳米颗粒有望成为一个有前景的平台，通过降低药物剂量和给药频率以及减少潜在副作用，递送治疗药物以获得良好的临床效果。（C）2013爱思唯尔有限公司。保留所有权利。
Bortezomib (BTZ) is the first clinically approved proteasome inhibitor for treating multiple human malignancies. However, the poor water-solubility and low stability of BTZ and the emergence of tumor resistance have severely restrained its therapeutic efficacy. Herein, we report the application of hollow mesoporous silica nanospheres (HMSNs) in encapsulating BTZ for drug delivery. In in vitro cell viability assay on human NSCLC H1299 cells, the half-maximum inhibiting concentration (IC50) of HMSNs-BTZ was 42% of that for free BTZ in 48 h treatments. In vivo tumor-suppression assay further indicated that HMSNs-BTZ (0.3 mg/kg) showed approximately 1.5 folds stronger anti-tumor activity than free BTZ. Furthermore, we report that more potent induction of cell cycle arrest and apoptotic cell death, along with promoted activation of Caspase 3 and autophagy might mechanistically underlie the improved antitumor efficacy of HMSNs-BTZ. Finally, the tumor-suppressing effect of HMSNs-BTZ was enhanced in the presence of wild-type p53 signaling, suggesting a potential enhancement in clinical efficacy with combined p53 gene therapy and BTZ-based chemotherapy. Therefore, the HMSNs-based nanoparticles are emerging as a promising platform to deliver therapeutic agents for beneficial clinical outcomes through lowering doses and frequency of drug administration and reducing potential side effects. (C) 2013 Elsevier Ltd. All rights reserved.