Targeting of Porous Hybrid Silica Nanoparticles to Cancer Cells
Targeting of Porous Hybrid Silica Nanoparticles to Cancer Cells
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DOI：
10.1021/nn800781r
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发表时间：
2009-01-01
期刊：
影响因子：
17.1
通讯作者：
Linden, Mika
中科院分区：
文献类型：
--
作者：
Rosenholm, Jessica M.;Meinander, Annika;Linden, Mika
通过聚乙二亚胺(PEI)的表面超支化聚合得到的介孔二氧化硅纳米颗粒，通过引入荧光和靶向基团进一步修饰，目的是特异性地靶向癌细胞。由于许多肿瘤细胞中叶酸受体的丰度高于正常细胞，叶酸被用作靶向配体。研究了表达不同水平叶酸受体的细胞株中颗粒的内化情况。用流式细胞术来定量每个细胞内化的纳米颗粒的平均数量。与表达低水平叶酸受体的正常细胞相比，表达叶酸受体的癌细胞内化的颗粒多五倍。不仅每个细胞内化了纳米颗粒的数量，而且内化了纳米颗粒的细胞比例也更高。因此，癌细胞内化的颗粒总数比正常细胞内化的颗粒总数高出约一个数量级，这一差异足以产生重大的生物学意义。此外，生物特异性标记的PEI-二氧化硅杂化颗粒被证明是无细胞毒性的，并且在共培养条件下也能够特异性地靶向表达叶酸受体的癌细胞。
Mesoporous silica nanoparticles functionalized by surface hyperbranching polymerization of poly(ethylene imine), PEI, were further modified by introducing both fluorescent and targeting moieties, with the aim of specifically targeting cancer cells. Owing to the high abundance of folate receptors in many cancer,cells as compared to normal cells, folic acid was used as the targeting ligand. The internalization of the particles in cell lines expressing different levels of folate receptors was studied. Flow cytometry was used to quantify the mean number of nanoparticles internalized per cell. Five times more particles were internalized by cancer cells expressing folate receptors as compared to the normal cells expressing low levels of the receptor. Not only the number of nanoparticles internalized per cell, but also the fraction of cells that had internalized nanoparticles was higher. The total number of particles internalized by the cancer cells was, therefore, about an order of magnitude higher than the total number of particles internalized by normal cells, a difference high enough to be of significant biological importance. In addition, the biospecifically tagged hybrid PEI-silica particles were shown to be noncytotoxic and able to specifically target folate receptor-expressing cancer cells also under coculture conditions.