Surface PEGylation of Mesoporous Silica Nanorods (MSNR): Effect on loading, release, and delivery of mitoxantrone in hypoxic cancer cells.

Surface PEGylation of Mesoporous Silica Nanorods (MSNR): Effect on loading, release, and delivery of mitoxantrone in hypoxic cancer cells.
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DOI:
10.1038/s41598-017-02531-4
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发表时间:
2017-05-23
期刊:
影响因子:
4.6
通讯作者:
Oupický D
Oupický D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wani A;Savithra GHL;Abyad A;Kanvinde S;Li J;Brock S;Oupický D

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介孔二氧化硅纳米材料显示出巨大的潜力,为癌症治疗提供化疗药物。开发可注射介孔二氧化硅制剂的关键挑战是胶体不稳定性、溶血和低效的药物装载和释放。在这项研究中,我们评估了PEG化的介孔二氧化硅纳米棒(MSNR)的溶血,胶体稳定性,米托蒽醌(MTX)的负载,在体外释放MTX,和缺氧条件下的细胞MTX交付的效果。我们发现PEG化在研究的浓度(0-10 mg/ml)下防止剂量依赖性溶血,并改善MSNR的胶体稳定性。观察到聚乙二醇化对MTX负载的负面影响,但与非聚乙二醇化颗粒相比,聚乙二醇化MSNR(PMSNR)显示出MTX释放增加。在低氧条件下,与常氧条件相比,观察到MTX和MTX负载的MSNR的IC 50降低。这些结果表明,MSNR可以将化疗药物MTX递送到肿瘤细胞并诱导有效的细胞杀伤。然而,由于观察到的对药物负载的不利影响,需要仔细研究PEG化的效果。
Mesoporous silica nanomaterials show great potential to deliver chemotherapeutics for cancer treatment. The key challenges in the development of injectable mesoporous silica formulations are colloidal instability, hemolysis and inefficient drug loading and release. In this study, we evaluated the effect of PEGylation of mesoporous silica nanorods (MSNR) on hemolysis, colloidal stability, mitoxantrone (MTX) loading, in vitro MTX release, and cellular MTX delivery under hypoxic conditions. We found that PEGylation prevented dose-dependent hemolysis in the concentrations studied (0–10 mg/ml) and improved colloidal stability of MSNR. A negative effect of PEGylation on MTX loading was observed but PEGylated MSNR (PMSNR) demonstrated increased MTX release compared to non-PEGylated particles. Under hypoxic conditions, a decrease in the IC50 of MTX and MTX-loaded MSNR was observed when compared to normoxic conditions. These results showed that MSNR could deliver the chemotherapeutic agent, MTX to tumor cells and induce effective cell killing. However, the effect of PEGylation needs to be carefully studied due to the observed adverse effect on drug loading.