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

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Bone Research 2017年第4期5卷 343-356页

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 School of Biomedical Engineering Shanghai Jiaotong UniverityShanghaiChina Department of Mechanical and Aerospace Engineering La JollaCAUSA Materials Science and Engineering Program La JollaCAUSA Department of Nanoengineering La JollaCAUSA Department of Chemical Engineering University of California San DiegoLa JollaCAUSA Departrnenf of Bioengineering La JollaCAUSA Department of Anesthesiology La JollaCAUSA Veterans Affairs San Diego Healthcare System San DiegoCAUSA Institute of Engineering in Medicine La JollaCAUSA

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

关键词： Multifunctional stimuli responsive polymer-gated iron

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