Faculty of Pharmacy, University of Sydney , NSW 2006, Australia.
Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University , Cheonan 330-714, Republic of Korea.
ACS Appl Mater Interfaces. 2016 Apr 13;8(14):8967-79. doi: 10.1021/acsami.6b00963. Epub 2016 Apr 4.
Currently there is a strong need for new drug delivery systems, which enable targeted and controlled function in delivering drugs while satisfying highly sensitive imaging modality for early detection of the disease symptoms and damaged sites. To meet these criteria we develop a system that integrates therapeutic and diagnostic capabilities (theranostics). Importantly, therapeutic efficacy of the system is enhanced by exploiting synergies between nanoparticles, drug, and hyperthermia. At the core of our innovation is near-infrared (NIR) responsive gold nanorods (Au) coated with drug reservoirs--mesoporous silica shell (mSi)--that is capped with thermoresponsive polymer. Such design of theranostics allows the detection of the system using computed tomography (CT), while finely controlled release of the drug is achieved by external trigger, NIR light irradiation--ON/OFF switch. Doxorubicin (DOX) was loaded into mSi formed on the gold core (Au@mSi-DOX). Pores were then capped with the temperature-sensitive poly(N-isopropylacrylamide)-based N-butyl imidazolium copolymer (poly(NIPAAm-co-BVIm)) resulting in a hybrid system-Au@mSi-DOX@P. A 5 min exposure to NIR induces polymer transition, which triggers the drug release (pores opening), increases local temperature above 43 °C (hyperthermia), and upregulates particle uptake (polymer becomes hydrophilic). The DOX release is also triggered by drop in pH enabling localized drug release when particles are taken up by cancer cells. Importantly, the synergies between chemo- and photothermal therapy for DOX-loaded theranostics were confirmed. Furthermore, higher X-ray attenuation value of the theranostics was confirmed via X-ray CT test indicating that the nanoparticles act as contrast agent and can be detected by CT.
目前,人们强烈需要新的药物输送系统,该系统能够在满足高度敏感的成像方式以早期检测疾病症状和受损部位的情况下,实现靶向和控制药物的功能。为了满足这些标准,我们开发了一种集治疗和诊断功能于一体的系统(治疗诊断一体化)。重要的是,通过利用纳米粒子、药物和热疗之间的协同作用,增强了系统的治疗效果。我们的创新核心是近红外(NIR)响应金纳米棒(Au),其表面涂有药物储存库——介孔硅壳(mSi),mSi 上覆盖有热敏聚合物。这种治疗诊断一体化设计允许使用计算机断层扫描(CT)来检测系统,而外部触发、近红外光照射(开/关开关)可实现药物的精细控制释放。阿霉素(DOX)被加载到涂覆在金核上的 mSi 中(Au@mSi-DOX)。然后,用温度敏感的基于聚(N-异丙基丙烯酰胺)的 N-丁基咪唑鎓共聚物(poly(NIPAAm-co-BVIm))封闭孔,得到混合系统-Au@mSi-DOX@P。5 分钟的近红外光照射会引起聚合物转变,从而触发药物释放(孔打开),使局部温度升高到 43°C 以上(热疗),并增加颗粒摄取量(聚合物变得亲水)。当粒子被癌细胞摄取时,pH 值下降也会触发 DOX 的释放,从而实现局部药物释放。重要的是,证实了载 DOX 的治疗诊断一体化的化学-光热协同作用。此外,通过 X 射线 CT 测试证实了治疗诊断一体化的 X 射线衰减值更高,表明纳米粒子可以作为造影剂,并且可以通过 CT 检测到。
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