Ultrastable, Redispersible, Small, and Highly Organomodified Mesoporous Silica Nanotherapeutics
Ultrastable, Redispersible, Small, and Highly Organomodified Mesoporous Silica Nanotherapeutics
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DOI：
10.1021/ja208567v
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发表时间：
2011-12-21
影响因子：
15
通讯作者：
Haynes, Christy L.
中科院分区：
文献类型：
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作者：
Lin, Yu-Shen;Abadeer, Nardine;Haynes, Christy L.
由于介孔二氧化硅纳米粒子在生物介质中存在严重的不可逆聚集，其分散性和稳定性较差，限制了其在生物医学领域的实际应用。为了解决这个问题，水热处理的介孔二氧化硅纳米粒子的小尺寸与双有机硅烷（亲水和疏水硅烷）表面修饰已被合成。通过透射电子显微镜、X射线衍射、N-2吸附-脱附、动态光散射、zeta电位和固态Si-29 NMR对这些高度有机改性的介孔二氧化硅纳米粒子进行了表征，并证明它们在生理温度下在模拟体液中非常稳定。此外，它们可以干燥成粉末状固体，并容易地在生物介质中再分散，保持其小尺寸至少15天。此外，这种制备方法可以扩展到合成可再分散的荧光和磁性介孔二氧化硅纳米粒子。高度稳定和可再分散的介孔二氧化硅NP在体外细胞测定期间显示出最小的毒性。最重要的是，两种类型的阿霉素，水溶性阿霉素和水溶性差的阿霉素，可以装载到这些高度稳定的介孔二氧化硅纳米粒子，这些载药纳米粒子也可以很好地再分散在水溶液中。与游离的水溶性阿霉素相比，在用水溶性阿霉素负载的纳米颗粒治疗后发现对宫颈癌（HeLa）细胞的增强的细胞毒性。这些结果表明，高度稳定，可再分散，和小介孔二氧化硅纳米粒子是有前途的代理在体内生物医学应用。
Practical biomedical application of mesoporous silica nanoparticles is limited by poor particle dispersity and stability due to serious irreversible aggregation in biological media. To solve this problem, hydrothermally treated mesoporous silica nanoparticles of small size with dual-organosilane (hydrophilic and hydrophobic silane) surface modification have been synthesized. These highly organomodified mesoporous silica nanoparticles were characterized by transmission electron microscopy, X-ray diffraction, N-2 adsorption-desorption, dynamic light scattering, zeta potential, and solid-state Si-29 NMR, and they prove to be very stable in simulated body fluid at physiological temperature. Additionally, they can be dried to a powdered solid and easily redispersed in biological media, maintaining their small size for a period of at least 15 days. Furthermore, this preparation method can be expanded to synthesize redispersible fluorescent and magnetic mesoporous silica nanoparticles. The highly stable and redispersible mesoporous silica NPs show minimal toxicity during in vitro cellular assays. Most importantly, two types of doxorubicin, water-soluble doxorubicin and poorly water-soluble doxorubicin, can be loaded into these highly stable mesoporous silica nanoparticles, and these drug-loaded nanoparticles can also be well-redispersed in aqueous solution. Enhanced cytotoxicity to cervical cancer (HeLa) cells was found upon treatment with water-soluble doxorubicin-loaded nanoparticles compared to free water-soluble doxorubicin. These results suggest that highly stable, redispersible, and small mesoporous silica nanoparticles are promising agents for in vivo biomedical applications.