Enzyme-/Redox-Responsive Mesoporous Silica Nanoparticles Based on Functionalized Dopamine as Nanocarriers for Cancer Therapy,ACS Omega

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Enzyme-/Redox-Responsive Mesoporous Silica Nanoparticles Based on Functionalized Dopamine as Nanocarriers for Cancer Therapy
ACS Omega ( IF 3.7 ) Pub Date : 2019-04-01 00:00:00 , DOI: 10.1021/acsomega.8b02537
Dandan Zhu ₁ , Chunlin Hu ₁ , Yuan Liu ₁ , Feng Chen ₁ , Zhen Zheng ₁ , Xinling Wang ₁

Affiliation

Mesoporous silica nanoparticles (MSNs) have been proved potential nanocarriers for efficient stimuli-triggered drug delivery systems (DDSs) in cancer therapy. We have developed a novel pepsin enzyme-responsive MSN based on mussel mimetic coating of dopamine for controlled release of drug delivery via a facile one-pot strategy. Herein, to improve drug release efficiency for cancer therapy, a novel dual-sensitive (enzyme- and redox-) MSN based on functionalized dopamine containing both peptide and disulfide bonds was designed and prepared. In detail, cystine-dopamine (Cy-DA) was newly synthesized and used as a monomer to self-polymerize into a coating on MSNs via simple a one-pot reaction to give rise to a chemotherapy drug [e.g., doxorubicin (DOX)] delivery system poly-Cy-DA-MSN. The in vitro cellular cytotoxicity tests of normal Marc-145 cells and HeLa cells showed that poly-Cy-DA-MSN was nontoxic, highly biocompatible, and suitable as drug carriers in controlled release DDS (CDDS). Because of the peptide and disulfide bonds in Cy-DA, the as-prepared DOX-loaded poly-Cy-DA-MSNs exhibited improving enzyme- and redox-responsive release property. Confocal laser scanning microscopy results showed that [email protected] transported by the cells through endocytosis mechanism and the cancer drug DOX were released mainly in the cytoplasm and also in cell nucleus. These results showed that poly-Cy-DA-MSN is a promising double-responsive CDDS for sustained cancer therapy.

中文翻译：

基于功能化多巴胺作为纳米载体的酶/氧化还原响应介孔二氧化硅纳米粒子。

介孔二氧化硅纳米粒子（MSNs）已被证明是潜在的纳米载体，可用于癌症治疗中有效的刺激触发药物递送系统（DDSs）。我们已经开发了一种新颖的胃蛋白酶对MSP的胃蛋白酶反应性MSN，该蛋白基于多巴胺的贻贝模拟涂层，通过一种简便的一锅策略控制药物释放。在此，为了提高用于癌症治疗的药物释放效率，设计并制备了一种新的基于功能性多巴胺的双敏感（酶和氧化还原）MSN，该多巴胺同时包含肽键和二硫键。详细地说，新合成了胱氨酸-多巴胺（Cy-DA），并用作单体，通过简单的一锅法反应自聚合成MSN上的涂层，从而产生了化疗药物[例如，阿霉素（DOX）]投放系统poly-Cy-DA-MSN。正常Marc-145细胞和HeLa细胞的体外细胞毒性测试表明，poly-Cy-DA-MSN无毒，高度生物相容性，适合作为控释DDS（CDDS）中的药物载体。由于Cy-DA中的肽键和二硫键，所制备的装载有DOX的聚Cy-DA-MSN表现出改善的酶和氧化还原响应释放特性。共聚焦激光扫描显微镜观察结果表明，通过内吞作用机制被细胞转运的[电子邮件保护]和抗癌药物DOX主要在细胞质中以及在细胞核中释放。这些结果表明，聚-Cy-DA-MSN是用于持续癌症治疗的有前途的双反应CDDS。由于Cy-DA中的肽键和二硫键，所制备的装载有DOX的聚Cy-DA-MSN表现出改善的酶和氧化还原响应释放特性。共聚焦激光扫描显微镜观察结果表明，通过内吞作用机制被细胞转运的[电子邮件保护]和抗癌药物DOX主要在细胞质中以及在细胞核中释放。这些结果表明，聚-Cy-DA-MSN是用于持续癌症治疗的有前途的双反应CDDS。由于Cy-DA中的肽键和二硫键，所制备的装载有DOX的聚Cy-DA-MSN表现出改善的酶和氧化还原响应释放特性。共聚焦激光扫描显微镜观察结果表明，通过内吞作用机制被细胞转运的[电子邮件保护]和抗癌药物DOX主要在细胞质中以及在细胞核中释放。这些结果表明，聚-Cy-DA-MSN是用于持续癌症治疗的有前途的双反应CDDS。

更新日期：2019-04-01

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