Multifunctional stimuli responsive polymer-gated iron and gold-embedded silica nano golf balls:Nanoshuttles for targeted on-demand theranostics

作     者：Liping Wang Grace Jang Deependra Kumar Ban Vrinda Sant Jay Seth Sami Kazmi Nirav Patel Qingqing Yang Joon Lee Woraphong Janetanakit Shanshan Wang Brian P Head Gennadi Glinsky Ratneshwar Lai 

作者机构：School of Biomedical EngineeringShanghai Jiaotong UniverityShanghaiChina Department of Mechanical and Aerospace EngineeringLa JollaCAUSA Materials Science and Engineering ProgramLa JollaCAUSA Department of NanoengineeringLa JollaCAUSA Department of Chemical Engineering University of CaliforniaSan DiegoLa JollaCAUSA Departrnenf of BioengineeringLa JollaCAUSA Department of AnesthesiologyLa JollaCAUSA Veterans Affairs San Diego Healthcare SystemSan DiegoCAUSA Institute of Engineering in MedicineLa JollaCAUSA 

出 版 物：《Bone Research》 (骨研究（英文版）)

年 卷 期：2017年第5卷第4期

页      面：343-356页

核心收录：

学科分类：08[工学] 080501[工学-材料物理与化学] 0805[工学-材料科学与工程（可授工学、理学学位）] 080502[工学-材料学] 

基　　金：supported in part by the National Institute on Aging of National Institutes of Health(Grant AG028709) the FUMEC and AMC for funds to support the 2016 summer research yield at the University of California in San Diego 

主　　题：Multifunctional stimuli responsive polymer gated iron 

摘      要：Multi-functional nanoshuttles for remotely targeted and on-demand delivery of therapeutic molecules and imaging to defined tissues and organs hold great potentials in personalized medicine, including precise early diagnosis, efficient prevention and therapy without toxicity. Yet, in spite of 25 years of research, there are still no such shuttles available. To this end, we have designed magnetic and gold nanoparticles （NP）-embedded silica nanoshuttles （MGNSs） with nanopores on their surface. Fluorescently labeled Doxombicin （DOX）, a cancer drug, was loaded in the MGNSs as a payload. DOX loaded MGNSs were encapsulated in heat and pH sensitive polymer P（NIPAM-co- MAA） to enable controlled release of the payload. Magnetically-guided transport of MGNSs was examined in： （a） a glass capillary tube to simulate their delivery via blood vessels; and （b） porous hydrogels to simulate their transport in composite human tissues, including bone, cartilage, tendon, muscles and blood-brain barrier {BBB）. The viscoelastic properties of hydrogels were examined by atomic force microscopy （AFM）. Cellular uptake of DOX- loaded MGNSs and the subsequent pH and temperature-mediated release were demonstrated in differentiated human neurons derived from induced pluripotent stem cells （iPSCs） as well as epithelial HeLa cells. The presence of embedded iron and gold NPs in silica shells and polymer-coating are supported by SEM and TEM. Fluorescence spectroscopy and microscopy documented DOX loading in the MGNSs. Time-dependent transport of MGNSs guided by an external magnetic field was observed in both glass capillary tubes and in the porous hydrogel. AFM results affirmed that the stiffness of the hydrogels model the rigidity range from soft tissues to bone. pH and temperature-dependent drug release analysis showed stimuli responsive and gradual drug release. Cells＇ viability MTT assays showed that MGNSs are non-toxic. The cell death from on-demand DOX release was observed in both neurons and ep