Ebrahimi Seyyed Mostafa, Karamat Iradmousa Mahdieh, Rashed Mahtab, Fattahi Yousef, Hosseinzadeh Ardakani Yalda, Bahadorikhalili Saeed, Bafkary Reza, Erfan Mohammad, Dinarvand Rassoul, Mahboubi Arash
Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Iran J Pharm Res. 2022 Sep 14;21(1):e130474. doi: 10.5812/ijpr-130474. eCollection 2022 Dec.
Stimuli-responsive drug delivery systems have been proven to be a promising strategy to enhance tumor localization, overcome multidrug resistance (MDR), and reduce the side effects of chemotherapy agents.
In this study, a temperature and redox dual stimuli-responsive system using mesoporous silica nanoparticles (MSNs) for targeted delivery of doxorubicin (DOX) was developed.
Mesoporous silica nanoparticles were capped with poly(N-isopropylacrylamide) (PNIPAM), a thermo-sensitive polymer, with atom transfer radical polymerization (ATRP) method, via disulfide bonds (DOX-MSN-S-S-PNIPAM) to attain a controlled system that releases DOX under glutathione-rich (GSH-rich) environments and temperatures above PNIPAM's lower critical solution temperature (LCST). Morphological and physicochemical properties of the nanoparticles were indicated using transmission electron microscopy (TEM), dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and Brunauer-Emmett-Teller (BET). The drug release tests were performed at 25°C and 41°C in the absence and presence of the DTT, and the obtained results confirmed the synergic effect of temperature and reductive agent on a dual responsive release profile with a 73% cumulative release at 41°C and reductive environment during 240 min.
The average loaded drug content and encapsulation efficacy were reported as 42% and 29.5% at the drug: nanoparticle ratio of 1.5: 1. In vitro cytotoxicity assays on MCF-7 cell lines indicated significant viability decreased in cells exposed to DOX-MSN-S-S-PNIPAM compared to the free drug (DOX).
Based on the results, DOX-MSN-S-S-PNIPAM has shown much more efficiency with stimuli-responsive properties in comparison to DOX on MCF-7 cancer cell lines.
刺激响应型药物递送系统已被证明是一种有前景的策略，可增强肿瘤定位、克服多药耐药性（MDR）并减少化疗药物的副作用。
在本研究中，开发了一种使用介孔二氧化硅纳米颗粒（MSN）靶向递送阿霉素（DOX）的温度和氧化还原双刺激响应系统。
通过原子转移自由基聚合（ATRP）方法，用聚（N-异丙基丙烯酰胺）（PNIPAM）（一种热敏聚合物）通过二硫键（DOX-MSN-S-S-PNIPAM）封端介孔二氧化硅纳米颗粒，以获得一种可控系统，该系统在富含谷胱甘肽（GSH）的环境和高于PNIPAM的低临界溶液温度（LCST）的温度下释放DOX。使用透射电子显微镜（TEM）、动态光散射（DLS）、能量色散X射线光谱（EDS）、热重分析（TGA）、差示扫描量热法（DSC）和布鲁瑙尔-埃米特-泰勒（BET）表征纳米颗粒的形态和物理化学性质。在有无二硫苏糖醇（DTT）的情况下于25°C和41°C进行药物释放测试，所得结果证实了温度和还原剂对双响应释放曲线的协同作用，在41°C和还原环境下240分钟内累积释放率为73%。
在药物与纳米颗粒比例为1.5:1时，平均载药量和包封率分别为42%和29.5%。对MCF-7细胞系的体外细胞毒性试验表明，与游离药物（DOX）相比，暴露于DOX-MSN-S-S-PNIPAM的细胞活力显著降低。
基于结果，与DOX相比，DOX-MSN-S-S-PNIPAM在MCF-7癌细胞系上表现出具有刺激响应特性的更高效率。
