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用于癌症治疗的γ辐射诱导聚乙二醇化顺铂的合成。

Synthesis of gamma radiation-induced PEGylated cisplatin for cancer treatment.

作者信息

González Torres Maykel, Cerna Cortez Jorge, Balam Muñoz Soto Rodrigo, Ríos Perez Alfonso, Pfeiffer Heriberto, Leyva Gómez Gerardo, Zúñiga Ramos Joaquín, Rivera Ana Leonor

机构信息

Escuela de Ingeniería y Ciencias, Instituto Tecnológico y de Estudios Superiores de Monterrey Campus Puebla 72453 Mexico

Laboratorio de Biotecnología, Instituto Nacional de Rehabilitación "Luís Guillermo Ibarra Ibarra" Ciudad de México 14389 Mexico

出版信息

RSC Adv. 2018 Oct 9;8(60):34718-34725. doi: 10.1039/c8ra06296j. eCollection 2018 Oct 4.

Abstract

The use of poly(ethylene glycol) (PEG) for the development of novel PEGylated biomolecules is playing an increasingly meaningful role in cancer treatment. Cisplatin (CDDP), is a useful chemotherapy drug. However, it is unclear whether PEGylated cisplatin (CDDPPEG) has potential as an alternative therapeutic agent. Here we prepared a PEGylated cisplatin by gamma radiation-induced synthesis, for the first time. PEGylated drugs were characterized using Raman and Fourier transform infrared spectroscopy (FTIR), as well as scanning electron microscopy coupled with Energy Dispersive X-ray (SEM/EDX). The results show that the cisplatin can be successfully PEGylated by this method. Furthermore, we show a proposal for the mechanism of the PEGylation reaction. The novel product exhibits therapeutic potential comparable to cisplatin at concentrations lower than 23 μM (Pt), causing differences in cell cycle checkpoints, which suggest changes in the signaling pathways that control growth arrest and cause apoptosis of A549 cells.

摘要

聚乙二醇(PEG)在新型聚乙二醇化生物分子的研发中,在癌症治疗方面正发挥着越来越重要的作用。顺铂(CDDP)是一种有效的化疗药物。然而,聚乙二醇化顺铂(CDDPPEG)是否具有作为替代治疗剂的潜力尚不清楚。在此,我们首次通过γ辐射诱导合成制备了聚乙二醇化顺铂。使用拉曼光谱和傅里叶变换红外光谱(FTIR)以及结合能量色散X射线的扫描电子显微镜(SEM/EDX)对聚乙二醇化药物进行了表征。结果表明,通过该方法可以成功地将顺铂聚乙二醇化。此外,我们提出了聚乙二醇化反应的机制。该新型产物在浓度低于23μM(Pt)时表现出与顺铂相当的治疗潜力,导致细胞周期检查点出现差异,这表明控制生长停滞并导致A549细胞凋亡的信号通路发生了变化。

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