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Facile preparation of multifunctional hollow silica nanoparticles and their cancer specific targeting effect

机译:多功能中空二氧化硅纳米粒子的简便制备及其特异性靶向作用

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Efficient delivery of therapeutics to tumor cells is one of the key issues in cancer therapy. In the present work, we have established a facile and unique chemical strategy for fabrication of highly biocompatible and water-dispersible multifunctional hollow silica nanoparticles (HSNPs). These mesoporous silica nano-particles, having ring-like morphology, were fabricated by the sol-gel method followed by selective etching of the inner inorganic core. Further, to accomplish cancer-specific targeting properties, folic acid was tethered to the surface of HSNPs through amide bond formation using the EDC/NHS coupling method. Thereafter, rhodamine B isothiocyanate (RITC) was conjugated to the HSNPs to endow the fluorescent property to the nanoparticles required for biological imaging applications. The successful formation of multifunctional HSNPs was confirmed by XRD, FTIR, zeta potential, TEM, FESEM, and BET surface area measurements. The average particle size of HSNPs was found to be 50 nm to 70 nm from TEM analysis, which is the desired size-range for drug-delivery vehicles. These HSNPs showed good mesoporous behavior and were found to be an excellent candidate for loading and releasing the anticancer drug doxorubicin (DOX). The bioactivity of the HSNPs was verified by biological assay including cell cytotoxicity by MTT assay, intracellular uptake by fluorescence microscopy, cell cycle analysis by fluorescence-activated cell sorting (FACS), and apoptosis study. Besides, the effect of salt concentration on the drug release performance was evaluated. An in vitro biological study revealed that these DOX-loaded folate-targeted HSNPs achieved excellent efficacy for simultaneously targeting and destroying cancer cells.
机译:将治疗剂有效地递送至肿瘤细胞是癌症治疗中的关键问题之一。在目前的工作中,我们为制造高度生物相容性和水分散性多功能中空二氧化硅纳米粒子(HSNPs)建立了一种简便而独特的化学策略。这些具有环状形态的中孔二氧化硅纳米粒子是通过溶胶-凝胶法,然后选择性蚀刻内部无机核而制成的。此外,为了实现癌症特异性靶向特性,使用EDC / NHS偶联方法通过酰胺键形成将叶酸拴在HSNP的表面。此后,将罗丹明B异硫氰酸酯(RITC)与HSNP偶联,以赋予生物成像应用所需的纳米粒子荧光性。 XRD,FTIR,ζ电位,TEM,FESEM和BET表面积测量证实了多功能HSNP的成功形成。通过TEM分析发现HSNP的平均粒径为50nm至70nm,这是药物递送载体的期望尺寸范围。这些HSNPs表现出良好的介孔行为,被发现是加载和释放抗癌药阿霉素(DOX)的极佳候选者。 HSNPs的生物活性通过生物学测定法进行了验证,包括通过MTT测定法测定细胞的细胞毒性,通过荧光显微镜观察细胞内摄取,通过荧光激活细胞分选法(FACS)进行的细胞周期分析以及凋亡研究。此外,评估了盐浓度对药物释放性能的影响。一项体外生物学研究表明,这些以DOX负载的叶酸靶向的HSNP在同时靶向和破坏癌细胞方面取得了卓越的功效。

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