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载钼簇的 PLGA 纳米粒:卵巢癌治疗的一种创新性诊疗策略。

Molybdenum cluster loaded PLGA nanoparticles: An innovative theranostic approach for the treatment of ovarian cancer.

机构信息

Univ Rennes, CNRS, ISCR (Institut des Sciences Chimiques de Rennes) - UMR 6226, F-35000 Rennes, France.

Univ Rennes, CNRS, ISCR (Institut des Sciences Chimiques de Rennes) - UMR 6226, F-35000 Rennes, France; CHU de Rennes, Pôle Pharmacie, F-35033 Rennes, France.

出版信息

Eur J Pharm Biopharm. 2018 Apr;125:95-105. doi: 10.1016/j.ejpb.2018.01.007. Epub 2018 Jan 31.

Abstract

We evaluate poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles embedding inorganic molybdenum octahedral cluster for photodynamic therapy of cancer (PDT). Tetrabutyl ammonium salt of MoBr cluster unit, (TBA)MoBr, presents promising photosensitization activity in the destruction of targeted cancer cells. Stable cluster loaded nanoparticles (CNPs) were prepared by solvent displacement method showing spherical shapes, zeta potential values around -30 mV, polydispersity index lower than 0.2 and sizes around 100 nm. FT-IR and DSC analysis revealed the lack of strong chemical interaction between the cluster and the polymer within the nanoparticles. In vitro release study showed that (TBA)MoBr was totally dissolved in 20 min, while CNPs were able to control the release of encapsulated cluster. In vitro cellular viability studies conducted on A2780 ovarian cancer cell line treated up to 72 h with cluster or CNPs did not show any sign of toxicity in concentrations up to 20 µg/ml. This concentration was selected for photo-activation test on A2780 cells and CNPs were able to generate oxygen singlet resulting in a decrease of the cellular viability up to 50%, respectively compared to non-activated conditions. This work presents (TBA)MoBr as a novel photosensitizer for PDT and suggests PLGA nanoparticles as an efficient delivery system intended for tumor targeting.

摘要

我们评估了聚(丙交酯-共-乙交酯)(PLGA)纳米粒子包埋无机钼八面体簇用于癌症的光动力疗法(PDT)。MoBr 八面体簇单元的四丁基铵盐(TBA)MoBr 在破坏靶向癌细胞方面表现出有前途的光敏化活性。通过溶剂置换法制备了稳定的负载簇的纳米粒子(CNPs),呈球形,zeta 电位值约为-30mV,多分散指数低于 0.2,粒径约为 100nm。FT-IR 和 DSC 分析表明,簇与纳米粒子内聚合物之间缺乏强的化学相互作用。体外释放研究表明,(TBA)MoBr 在 20 分钟内完全溶解,而 CNPs 能够控制封装簇的释放。在浓度高达 20μg/ml 时,对 A2780 卵巢癌细胞系进行长达 72 小时的簇或 CNPs 处理的体外细胞活力研究没有显示出任何毒性迹象。选择该浓度对 A2780 细胞进行光激活测试,与非激活条件相比,CNPs 能够分别产生氧单重态,导致细胞活力降低至 50%左右。这项工作提出了(TBA)MoBr 作为 PDT 的新型光敏剂,并提出 PLGA 纳米粒子作为用于肿瘤靶向的有效递药系统。

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