A dual-sensitive poly(amino acid)/hollow mesoporous silica nanoparticle-based anticancer drug delivery system with a rapid charge-reversal property
A dual-sensitive poly(amino acid)/hollow mesoporous silica nanoparticle-based anticancer drug delivery system with a rapid charge-reversal property
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具有快速电荷反转特性的双敏感聚氨基酸/中空介孔二氧化硅纳米粒子抗癌药物递送系统
DOI：
10.1016/j.jddst.2021.102817
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发表时间：
2021-09-06
影响因子：
5
通讯作者：
Li, Cao
中科院分区：
文献类型：
--
作者：
Xu, Xiangyu;Duan, Junlin;Li, Cao
这种由负到正的表面电荷反转能力可以减少细胞对纳米抗癌药物递送系统(DDSS)的非特异性摄取，并增强癌细胞的内吞能力。本文报道了一种具有快速电荷反转特性的新型双灵敏抗癌药物DDS。以载药量高的中空介孔二氧化硅纳米颗粒(HMSN)为“纳米容器”，对药物盐酸阿霉素(DOX)进行包覆，再通过氧化还原敏感的二硫键与聚天冬氨酸接枝-1-(3-氨基丙基)咪唑(PASP-g-API)包覆，得到DDS DOX@HMSN-SS-PASP-API。咪唑基团在pH为7.4时未被电离，导致DDS表面带负电荷。但在微酸性的肿瘤微环境中，咪唑基团的电离迅速逆转了载体的表面电荷，从而更好地被癌细胞摄取。胞吞作用后，连接PASP-g-API和HMSN的二硫键在细胞间的还原环境中被打断，导致DOX释放。体外实验证明了载体的快速电荷反转特性，细胞实验证明载体在弱酸性环境中更容易进入癌细胞。药物释放研究表明，在谷胱甘肽浓度为10 mM的情况下，DOX@HMSN-SS-PASP-API在5天内可以释放出与97%负载的DOX相似的药物，表明其对氧化还原反应敏感。在所有DDS组中，pH 6.5的DOX@HMSN-SS-PASP-API的治疗效果最好。这种具有快速电荷反转特性的双重灵敏体系是抗癌DDSS研究的一个很好的补充。
The negative-to-positive surface charge-reversal capability introduced can reduce the nonspecific cellular uptake of the nanosized anticancer drug delivery systems (DDSs) and enhance the endocytosis capability by cancer cells. In this article, a novel dual-sensitive anticancer DDS with a rapid charge-reversal property was reported. Hollow mesoporous silica nanoparticle (HMSN) with a high drug loading capacity was applied as the "nanocontainer" to package the drug doxorubicin hydrochloride (DOX), then was coated by poly(aspartic acid)-graft-1-(3-aminopropyl) imidazole (PASP-g-API) through the redox-sensitive disulfide bond to obtain the DDS DOX@HMSN-SS-PASP-API. The imidazole group was not ionized at pH 7.4, resulting in a negatively charged surface of the DDS. But in the slightly acidic tumor microenvironment, the ionization of the imidazole group rapidly reversed the surface charge of the carriers for better uptake by cancer cells. After the endocytosis, the disulfide bond linking PASP-g-API and HMSN could be interrupted in the reducing environment intercellular, leading to the DOX release. The rapid charge-reversal property of the carriers was demonstrated by the in vitro studies, and the cell experiments proved that the carriers could enter the cancer cells much easier in the weakly acidic environment. Drug release studies indicated that DOX@HMSN-SS-PASP-API could release similar to 97% loaded DOX within 5 days with the glutathione concentration of 10 mM, demonstrating its sensitivity to redox. Also, DOX@HMSN-SS-PASP-API at pH 6.5 showed the best therapeutic effect among all the DDS groups. This dual sensitive system with a rapid charge-reversal property should be a good complement to the researches of anti-cancer DDSs.