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载药介孔硅席夫碱键合型毒副作用减毒复合物用于耐药性癌症的化疗。

Toxicity-attenuated mesoporous silica Schiff-base bonded anticancer drug complexes for chemotherapy of drug resistant cancer.

机构信息

School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, China; Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, 211166, Nanjing, China.

Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, 211166, Nanjing, China.

出版信息

Colloids Surf B Biointerfaces. 2021 Sep;205:111839. doi: 10.1016/j.colsurfb.2021.111839. Epub 2021 May 11.

Abstract

Multidrug resistance (MDR), evoked by improper chemotherapeutic practices, poses a serious threat to public health, which leads to increased medical burdens and weakened curative effects. Taking advantage of the enhanced pharmaceutical effect of Schiff base compounds, an aldehyde-modified mesoporous silica SBA-15 (CHO-SBA-15)-bonded anticancer drug combined with doxorubicin hydrochloride (DOX) was synthesized via a Schiff base reaction. Due to the acid-sensitive imine bonds formed between CHO-SBA-15 and DOX, the as-prepared nanocomposites exhibited pH-responsive drug releasing behaviours, resulting in a more enhanced cytotoxic effect on DOX-resistant tumour cells than that of free drugs. Notably, the in vivo studies indicated that mice treated with CHO-SBA-15/DOX composites evidently showed more attenuated systemic toxicity than the free drug molecules. The siliceous mesopore Schiff base-bonded anticancer drug nanocomposite, with minimal chemical modifications, provides a simplified yet efficient therapeutic nanoplatform to deal with drug-resistant cancer.

摘要

多药耐药性(MDR)是由不当的化疗实践引起的,对公共健康构成严重威胁,导致医疗负担增加和治疗效果减弱。利用席夫碱化合物的增强药物作用,通过席夫碱反应合成了醛修饰的介孔硅 SBA-15(CHO-SBA-15)键合抗癌药物与盐酸多柔比星(DOX)结合。由于 CHO-SBA-15 和 DOX 之间形成了酸敏感的亚胺键,所制备的纳米复合材料表现出 pH 响应性药物释放行为,对多柔比星耐药肿瘤细胞的细胞毒性作用比游离药物更强。值得注意的是,体内研究表明,用 CHO-SBA-15/DOX 复合材料治疗的小鼠表现出比游离药物分子明显更低的全身毒性。硅质介孔席夫碱键合抗癌药物纳米复合材料,经过最小的化学修饰,提供了一种简化而有效的治疗性纳米平台,以应对耐药性癌症。

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