Cancer-Cell-Specific Induction of Apoptosis Using Mesoporous Silica Nanoparticles as Drug-Delivery Vectors
Cancer-Cell-Specific Induction of Apoptosis Using Mesoporous Silica Nanoparticles as Drug-Delivery Vectors
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DOI：
10.1002/smll.200902355
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发表时间：
2010-06-06
期刊：
影响因子：
13.3
通讯作者：
Linden, Mika
中科院分区：
文献类型：
--
作者：
Rosenholm, Jessica M.;Peuhu, Emilia;Linden, Mika
报道了以聚乙烯亚胺功能化介孔二氧化硅颗粒为载体，将化疗药物甲氨蝶呤(MTX)定向输送至癌细胞。由于其对叶酸受体的高亲和力，其在癌细胞中的表达增加，MTX既是靶向配体，又是细胞毒剂。因此，相对于游离的MTX，在非靶向健康细胞系中没有观察到非特异性MTX诱导的凋亡的粒子浓度，而相应数量的游离药物对两种细胞系的影响相等时，可以观察到相对于游离MTX的癌细胞凋亡增强(程序性细胞死亡)。在观察期间(长达72小时)，药物颗粒在内切/溶酶体中保持分隔状态，而药物只有在细胞进入时才从颗粒中释放，从而诱导靶细胞的选择性凋亡。由于MTX主要附着在颗粒表面，另一个优点是所提供的载体设计允许将额外的药物吸附(装载)到基于药物组合的治疗的孔网络中。
Targeted delivery of the chemotherapeutic agent methotrexate (MTX) to cancer cells using poly(ethyleneimine)-functionalized mesoporous silica particles as drug-delivery vectors is reported. Due to its high affinity for folate receptors, the expression of which is elevated in cancer cells, MTX serves as both a targeting ligand and a cytotoxic agent. Enhanced cancer-cell apoptosis (programmed cell death) relative to free MTX is thus observed at particle concentrations where nonspecific MTX-induced apoptosis is not observed in the nontargeted healthy cell line, while corresponding amounts of free drug affect both cell lines equally. The particles remain compartmentalized in endo-/lysosomes during the time of observation (up to 72 h), while the drug is released from the particle only upon cell entry, thereby inducing selective apoptosis in the target cells. As MTX is mainly attached to the particle surface, an additional advantage is that the presented carrier design allows for adsorption (loading) of additional drugs into the pore network for therapies based on a combination of drugs.