de Miguel Laura, Popa Iuliana, Noiray Magali, Caudron Eric, Arpinati Ludovica, Desmaele Didier, Cebrián-Torrejón Gerardo, Doménech-Carbó Antonio, Ponchel Gilles
Institut Galien Paris-Sud, CNRS UMR 8612, Université Paris-Sud, 5 rue Jean Baptiste Clément, 92296, Chatenay-Malabry, France,
Pharm Res. 2015 May;32(5):1794-803. doi: 10.1007/s11095-014-1576-z. Epub 2014 Dec 12.
Nanoparticles with prolonged residence time in bone constitute a valuable strategy for bone disease treatments. The aim of this work was to synthesise a simple nanoparticulate system exhibiting both anticancer and hydroxyapatite binding properties for potential bone cancer applications.
The amphiphilic copolymer poly(γ-benzyl-glutamate)-block-poly(glutamic acid) (PBLG-b-PGlu) was synthetised by ring opening polymerization and nanoparticles were obtained by a simple nanoprecipitation method. Nanoparticles were characterized in terms of cisplatin interaction, association, and release as well as interaction with hydroxyapatite and their cytoxicity was studied in three prostate cancer cell lines.
PBLG-b-PGlu nanoparticles of ~50 nm in size were successfully prepared. They could display for the first time dual hydroxyapatite binding and anticancer properties mediated by the PGlu moiety. They could complex cisplatin at a drug loading content of 6.2% (w/w). Cisplatin release was triggered by physiological concentrations of chloride ions according to an almost zero order kinetics during 14 days. Simultaneously, these nanoparticles showed in vitro hydroxyapatite binding. Finally, they were shown to exert a cytotoxic effect in three prostate cancer cell lines that potentially metastasize to bone.
These properties suggest the potential utility of cisplatin-loaded PBLG-b-PGlu nanoparticles as carrier systems for the treatment of bone metastases.
在骨中具有较长停留时间的纳米颗粒是治疗骨疾病的一种有价值的策略。本研究的目的是合成一种简单的纳米颗粒系统，该系统兼具抗癌和羟基磷灰石结合特性，用于潜在的骨癌应用。
通过开环聚合合成两亲性共聚物聚（γ-苄基谷氨酸）-嵌段-聚（谷氨酸）（PBLG-b-PGlu），并通过简单的纳米沉淀法获得纳米颗粒。对纳米颗粒进行顺铂相互作用、缔合和释放以及与羟基磷灰石相互作用的表征，并在三种前列腺癌细胞系中研究其细胞毒性。
成功制备了尺寸约为50 nm的PBLG-b-PGlu纳米颗粒。它们首次能够展示由PGlu部分介导的双重羟基磷灰石结合和抗癌特性。它们可以在药物负载量为6.2%（w/w）时络合顺铂。在14天内，生理浓度的氯离子以几乎零级动力学触发顺铂释放。同时，这些纳米颗粒在体外表现出与羟基磷灰石的结合。最后，它们在三种可能转移至骨的前列腺癌细胞系中显示出细胞毒性作用。
这些特性表明负载顺铂的PBLG-b-PGlu纳米颗粒作为治疗骨转移的载体系统具有潜在的应用价值。
