In vitro evaluation of folic acid-conjugated redox-responsive mesoporous silica nanoparticles for the delivery of cisplatin.
In vitro evaluation of folic acid-conjugated redox-responsive mesoporous silica nanoparticles for the delivery of cisplatin.
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DOI：
10.2147/ijn.s118196
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发表时间：
2016
影响因子：
8
通讯作者：
Vivero-Escoto JL
中科院分区：
文献类型：
--
作者：
Alvarez-Berríos MP;Vivero-Escoto JL
由于顺铂（IV）前药的低毒性和反应性，其用于递送顺铂的用途已获得显著关注。最近的研究表明，靶向顺铂（IV）-前药纳米粒为基础的输送系统可以提高顺铂（IV）前药的内化。我们假设，叶酸共轭介孔二氧化硅纳米粒子（MSNs）含有顺铂（IV）的前药可以靶向癌细胞，过表达叶酸受体，并提供细胞内还原后的活性顺铂药物。为了证明这一假设，使用流式细胞术和共聚焦显微镜在HeLa癌细胞中进行内化和定位研究。还评价了MSN从内溶酶体隔室逃逸的能力、DNA加合物的形成以及MSN的细胞毒性作用。我们的结果证实，这种基于MSN的递送平台能够将顺铂递送到HeLa细胞的胞质溶胶中，诱导DNA加合物和随后的细胞死亡。
The use of cisplatin(IV) prodrugs for the delivery of cisplatin have gained significant attention, because of their low toxicity and reactivity. Recent studies have shown that targeted cisplatin(IV)-prodrug nanoparticle-based delivery systems can improve the internalization of the cisplatin(IV) prodrug. We hypothesized that folic acid-conjugated mesoporous silica nanoparticles (MSNs) containing cisplatin(IV) prodrug could target cancer cells that overexpress the folate receptor and deliver the active cisplatin drug upon intracellular reduction. To prove this hypothesis, internalization and localization studies in HeLa cancer cells were performed using flow cytometry and confocal microscopy. The ability of MSNs to escape from the endolysosomal compartments, the formation of DNA adducts, and the cytotoxic effects of the MSNs were also evaluated. Our results confirmed that this MSN-based delivery platform was capable of delivering cisplatin into the cytosol of HeLa cells, inducing DNA adducts and subsequent cell death.