Methotrexate-immobilized poly(ethylene glycol) magnetic nanoparticles for MR imaging and drug delivery
Methotrexate-immobilized poly(ethylene glycol) magnetic nanoparticles for MR imaging and drug delivery
复制标题
DOI：
10.1002/smll.200600009
复制
发表时间：
2006-06-01
期刊：
影响因子：
13.3
通讯作者：
Zhang, MQ
中科院分区：
文献类型：
--
作者：
Kohler, N;Sun, C;Zhang, MQ
我们报道了一种生物稳定的氨甲喋呤固定的氧化铁纳米药物载体的开发，该载体可能通过磁共振成像用于药物释放的实时监测。通过聚乙二醇自组装单分子膜(PEGSAM)将甲氨蝶呤(MTX)固定在纳米颗粒表面。以9L胶质瘤细胞为模型，研究了纳米粒-药物结合物(NP-PEG-MTX)对靶细胞的杀伤作用。细胞摄取实验表明，脑胶质瘤细胞对NP-PEG-MTX偶联物的摄取明显高于对照纳米粒。用不同浓度的NP-PEG-MTX培养的9L细胞的磁共振成像显示明显的对比增强。在9L细胞中，NP-PEG-MTX对游离MTX表现出较高的细胞毒作用。用甲氨蝶呤解毒剂亚叶酸钙对暴露于NP-PEG-MTX或游离MTX的细胞进行了挽救，实验证实了NP-PEG-MTX结合物和NP-PEG-MTX结合物上的MTX的生物相容性是其对靶细胞的细胞毒性的真正来源。电子衍射结果表明，NP-PEG-MTX偶联物已内化到9L细胞质中，并在胞质中保持晶体结构长达144h。这种长时间的微粒滞留可能允许医生在延长的治疗过程中对暴露于NP-PEG-MTX结合物的肿瘤细胞进行成像。
We report the development of a biostable methotrexate-immobilized iron oxide nanoparticle drug carrier that may potentially be used for real-time monitoring of drug delivery through magnetic resonance imaging. Methotrexate (MTX) was immobilized on the nanoparticle surface via a poly(ethylene glycol) self-assembled monolayer (PEG SAM). The cytotoxicity of the nanoparticle-drug conjugate (NP-PEG-MTX) to target cells was studied with 9L glioma cells. Cellular uptake experiments showed that the uptake of NP-PEG-MTX conjugates by glioma cells was considerably higher than that of control nanoparticles. Magnetic resonance imaging in 9L cells cultured with NP-PEG-MTX of various concentrations showed significant contrast enhancement. NP-PEG-MTX demonstrated higher cytotoxicity in 9L cells to free MTX in vitro. Leucovorin, an MTX antidote, was used to rescue the cells that had been exposed to NP-PEG-MTX or free MTX, and the experiment verified the biocompatibility of NP-PEG-MTX conjugates and the MTX on NP-PEG-MTX conjugates to be the trite source of the cytotoxicity to the target cells. TEM results showed that NP-PEG-MTX conjugates were internalized into the 9L cellular cytoplasm and retained its crystal structure therein for up to 144 h, as identified by electron diffraction. This prolonged particle retention may allow physicians to image tumor cells exposed to the NP-PEG-MTX conjugate over an extended therapeutic time course.