Antitumor properties of platinum(IV) prodrug-loaded silk fibroin nanoparticles
Antitumor properties of platinum(IV) prodrug-loaded silk fibroin nanoparticles
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DOI：
10.1039/c5dt00378d
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发表时间：
2015-01-01
影响因子：
4
通讯作者：
Ruiz, Jose
中科院分区：
文献类型：
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作者：
Abel Lozano-Perez, A.;Gil, Ana L.;Ruiz, Jose
铂（IV）络合物利用肿瘤内发生的排他性条件来进行其细胞毒性活性。另一方面，丝素蛋白具有使其作为生物材料非常有趣的天然性质：高生物相容性、生物降解性、低免疫原性、高细胞渗透能力和高反应性表面。本文报道了负载疏水性Pt（IV）配合物cis，cis，trans-[Pt（NH3）（2）Cl-2（O2 CC 6 H5）（2）]（PtBz）的丝素蛋白纳米颗粒（SFNs）的制备。只有一小部分负载的PtBz被释放（48小时后小于10%）。PtBz-SFN对人卵巢癌A2780细胞及其顺铂耐药变异体A2780 cisR细胞具有较强的细胞毒作用。有趣的是，PtBz-SFN对三阴性乳腺肿瘤细胞系MDA-MB-231以及SK-BR-3和MCF-7具有非常强的细胞毒性（纳摩尔IC 50值），同时保持了优异的选择性指数。
Platinum(IV) complexes take advantage of the exclusive conditions that occur within the tumor to carry out their cytotoxic activity. On the other hand, silk fibroin has natural properties which make it very interesting as a biomaterial: high biocompatibility, biodegradability, low immunogenicity, high cellular penetration capacity and high reactive surface. Herein we report the preparation of silk fibroin nanoparticles (SFNs) loaded with the hydrophobic Pt(IV) complex cis,cis,trans-[Pt(NH3)(2)Cl-2(O2CC6H5)(2)] (PtBz). Only a small fraction of the loaded PtBz is released (less than 10% after 48 h). PtBz-SFNs trigger strong cytotoxic effects against human ovarian carcinoma A2780 cells and their cisplatin-resistant variant A2780cisR cells. Interestingly, PtBz-SFNs are very cytotoxic (nanomolar IC50 values) toward the triple negative breast tumor cell line MDA-MB-231, and also toward SK-BR-3 and MCF-7, while maintaining an excellent selectivity index.