Synthesis of biomolecule-modified mesoporous silica nanoparticles for targeted hydrophobic drug delivery to cancer cells.
Synthesis of biomolecule-modified mesoporous silica nanoparticles for targeted hydrophobic drug delivery to cancer cells.
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DOI：
10.1002/smll.201002300
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发表时间：
2011-07-04
期刊：
影响因子：
13.3
通讯作者：
Zink, Jeffrey I.
中科院分区：
文献类型：
--
作者：
Ferris, Daniel P.;Lu, Jie;Gothard, Chris;Yanes, Rolando;Thomas, Courtney R.;Olsen, John-Carl;Stoddart, J. Fraser;Tamanoi, Fuyuhiko;Zink, Jeffrey I.
描述了将疏水药物输送和生物分子靶向与介孔二氧化硅纳米颗粒相结合的合成方法。转铁蛋白和环-RGD多肽利用不同的技术共价连接到纳米颗粒上，并在原发和转移的癌细胞之间提供选择性。用荧光显微镜和流式细胞术检测细胞对靶向颗粒摄取的增加。转铁蛋白修饰的二氧化硅纳米颗粒在PANC-1癌细胞对颗粒的摄取方面比正常的HFF细胞表现出更强的摄取。通过将转铁蛋白受体质粒导入正常的HFF细胞系，进一步研究了这些颗粒的内吞途径，与未修饰的HFF细胞相比，这导致了颗粒内吞作用的增加。通过设计和连接合成的环-RGD，通过增强转移癌细胞对颗粒的摄取，实现了原代癌细胞(BT-549)和转移癌细胞(MDA-MB 435)之间的选择性。将疏水药物喜树碱掺入这两种生物分子靶向纳米粒中，与游离药物和非靶向粒子相比，靶向癌细胞的死亡率会增加。这些结果表明，成功的生物分子靶向疏水药物输送载体，选择性地靶向特定的癌细胞，并导致增强的药物输送和细胞死亡率。
Synthetic methodologies integrating hydrophobic drug delivery and biomolecular targeting with mesoporous silica nanoparticles are described. Transferrin and cyclic-RGD peptides are covalently attached to the nanoparticles utilizing different techniques and provide selectivity between primary and metastatic cancer cells. The increase in cellular uptake of the targeted particles is examined using fluorescence microscopy and flow cytometry. Transferrin-modified silica nanoparticles display enhancement in particle uptake by Panc-1 cancer cells over that of normal HFF cells. The endocytotic pathway for these particles is further investigated through plasmid transfection of the transferrin receptor into the normal HFF cell line, which results in an increase in particle endocytosis as compared to unmodified HFF cells. By designing and attaching a synthetic cyclic-RGD, selectivity between primary cancer cells (BT-549) and metastatic cancer cells (MDA-MB 435) is achieved with enhanced particle uptake by the metastatic cancer cell line. Incorporation of the hydrophobic drug Camptothecin into these two types of biomolecular-targeted nanoparticles causes an increase in mortality of the targeted cancer cells compared to that caused by both the free drug and nontargeted particles. These results demonstrate successful biomolecular-targeted hydrophobic drug delivery carriers that selectively target specific cancer cells and result in enhanced drug delivery and cell mortality.
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