Methotrexate-modified superparamagnetic nanoparticles and their intracellular uptake into human cancer cells
Methotrexate-modified superparamagnetic nanoparticles and their intracellular uptake into human cancer cells
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DOI：
10.1021/la0503451
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发表时间：
2005-09-13
期刊：
影响因子：
3.9
通讯作者：
Zhang, MQ
中科院分区：
文献类型：
--
作者：
Kohler, N;Sun, C;Zhang, MQ
开发了一种磁性纳米颗粒缀合物，其可以潜在地用作磁共振成像中的对比增强剂和受控药物递送中的药物载体，靶向于癌症诊断和治疗。这种结合物是由与甲氨蝶呤（MTX）共价结合的氧化铁纳米颗粒制成的，甲氨蝶呤是一种化疗药物，可以靶向许多表面被叶酸受体过度表达的癌细胞。纳米粒子首先用（3-氨丙基）-三甲氧基硅烷进行表面改性以形成自组装单层，随后通过MTX上的羧酸端基和粒子表面上的胺基之间的酰胺化与MTX缀合。药物释放实验表明，MTX在低pH条件下从纳米颗粒裂解，模拟溶酶体中的细胞内条件。在人乳腺癌细胞（MCF-7）和人宫颈癌细胞（HeLa）中的细胞活力研究进一步证明了通过细胞内酶的作用在靶细胞内化学裂解MTX的有效性。提出的细胞内运输模型通过纳米颗粒摄取研究得到支持，该研究表明表达人叶酸受体的细胞比阴性对照细胞内化更高水平的纳米颗粒。
A magnetic nanoparticle conjugate was developed that can potentially serve both as a contrast enhancement agent in magnetic resonance imaging and as a drug carrier in controlled drug delivery, targeted at cancer diagnostics and therapeutics. The conjugate is made of iron oxide nanoparticles covalently bound with methotrexate (MTX), a chemotherapeutic drug that can target many cancer cells whose surfaces are overexpressed by folate receptors. The nanoparticles were first surface-modified with (3-aminopropyl)-trimethoxysilane to form a self-assembled monolayer and subsequently conjugated with MTX through amidation between the carboxylic acid end groups on MTX and the amine groups on the particle surface. Drug release experiments demonstrated that MTX was cleaved from the nanoparticles under low pH conditions mimicking the intracellular conditions in the lysosome. Cellular viability studies in human breast cancer cells (MCF-7) and human cervical cancer cells (HeLa) further demonstrated the effectiveness of such chemical cleavage of MTX inside the target cells through the action of intracellular enzymes. The intracellular trafficking model proposed was supported through nanoparticle uptake studies which demonstrated that cells expressing the human folate receptor internalized a higher level of nanoparticles than negative control cells.