Multifunctional stimuli responsive polymer-gated iron and gold-embedded silica nano golf balls: Nanoshuttles for targeted on-demand theranostics.
Multifunctional stimuli responsive polymer-gated iron and gold-embedded silica nano golf balls: Nanoshuttles for targeted on-demand theranostics.
复制标题
DOI：
10.1038/boneres.2017.51
复制
发表时间：
2017
期刊：
影响因子：
12.7
通讯作者：
Lal R
中科院分区：
文献类型：
--
作者：
Wang L;Jang G;Ban DK;Sant V;Seth J;Kazmi S;Patel N;Yang Q;Lee J;Janetanakit W;Wang S;Head BP;Glinsky G;Lal R
多功能纳米梭用于远程靶向和按需递送治疗分子和成像到定义的组织和器官，在个性化医疗中具有巨大的潜力，包括精确的早期诊断，有效的预防和无毒性的治疗。然而，尽管经过25年的研究，仍然没有这样的航天飞机可用。为此，我们设计了磁性和金纳米粒子（NP）嵌入的二氧化硅纳米梭（MGNS），其表面上具有纳米孔。荧光标记的阿霉素（DOX），一种抗癌药物，作为有效载荷装载在MGNS中。将负载DOX的MGNS包封在热和pH敏感性聚合物P（NIPAM-co-MAA）中以实现有效载荷的受控释放。在（a）玻璃毛细管中检查MGNS的磁引导运输，以模拟它们经由血管的递送;和（B）多孔水凝胶，以模拟它们在复合人体组织中的运输，所述复合人体组织包括骨、软骨、肌腱、肌肉和血脑屏障（BB B）。用原子力显微镜（AFM）研究了水凝胶的粘弹性能。在源自诱导多能干细胞（iPSC）以及上皮HeLa细胞的分化的人神经元中证明了细胞摄取DOX负载的MGNS以及随后的pH和温度介导的释放。通过SEM和TEM支持在二氧化硅壳和聚合物涂层中嵌入的铁和金纳米颗粒的存在。荧光光谱法和显微镜检查记录了MGNS中的DOX负载。在玻璃毛细管和多孔水凝胶中观察到由外部磁场引导的MGNS的时间依赖性运输。AFM结果证实，水凝胶的刚度模型的刚度范围从软组织到骨。pH和温度依赖性药物释放分析显示刺激响应和逐渐的药物释放。MTT法检测细胞活力表明MGNS无毒性。在神经元和上皮细胞中均观察到来自按需DOX释放的细胞死亡，即使药物释放效率在神经元中更高。因此，智能纳米梭的开发对于治疗诊断学的有效载荷的受控递送和在特定组织和器官（例如，骨、软骨、腱、骨髓、心脏、肺、肝、肾和脑）中的精确引导运输具有显著的转化潜力，以用于高效的个性化医学应用。
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 Doxorubicin (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 epithelial cells even though the drug release efficiency was higher in neurons. Therefore, development of smart nanoshuttles have significant translational potential for controlled delivery of theranostics’ payloads and precisely guided transport in specified tissues and organs (for example, bone, cartilage, tendon, bone marrow, heart, lung, liver, kidney, and brain) for highly efficient personalized medicine applications.
登录
查看更多内容
影响因子：
8
作者：
Gu W;Wu C;Chen J;Xiao Y
通讯作者：
Xiao Y
DOI：
10.1016/j.nano.2014.06.010
发表时间：
2014-11
期刊：
Nanomedicine : nanotechnology, biology, and medicine
影响因子：
--
作者：
Kwok J;Grogan S;Meckes B;Arce F;Lal R;D'Lima D
通讯作者：
D'Lima D
影响因子：
3.9
作者：
Karg, Matthias;Pastoriza-Santos, Isabel;Hellweg, T.
通讯作者：
Hellweg, T.
影响因子：
9.7
作者：
Casciaro, Bruno;Moros, Maria;Mangoni, Maria Luisa
通讯作者：
Mangoni, Maria Luisa
影响因子：
8
作者：
Wang C;Zhang K;Zhou Z;Li Q;Shao L;Hao RZ;Xiao R;Wang S
通讯作者：
Wang S