The first-line chemotherapy drug that is used to treat pancreatic ductal adenocarcinoma is gemcitabine. Unfortunately, its effectiveness is hampered by its chemo-resistance, low vascularization and drug biodistribution limitations in the tumor microenvironment. Novel nanotherapeutics must be developed in order to improve the prognosis for patients with pancreatic cancer. We developed a synthetic methodology for obtaining a water-soluble nanoconjugate of a [60]fullerene-glycine derivative with the FDA-approved drug gemcitabine (nanoC60GEM). The proposed synthetic protocol enables a highly water-soluble [60]fullerene-glycine derivative (6) to be obtained, which was next successfully conjugated with gemcitabine using the EDCI/NHS carbodiimide protocol. The desired nanoconjugate was characterized using mass spectrometry and DLS, IR and XPS techniques. The photogeneration of singlet oxygen and the superoxide anion radical were studied by measuring 1O2 near-infrared luminescence at 1270 nm, followed by spin trapping of the DMPO adducts by EPR spectroscopy. The biological assays that were performed indicate that there is an inhibition of the cell cycle in the S phase and the induction of apoptosis by nanoC60GEM. In this paper, we present a robust approach for synthesizing a highly water-soluble [60]fullerene nanoconjugate with gemcitabine. The performed biological assays on pancreatic cancer cell lines demonstrated cytotoxic effects of nanoC60GEM, which were enhanced by the generation of reactive oxygen species after blue LED irradiation of synthesized fullerene nanomaterial.

中文翻译：

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[60]富勒烯纳米偶联物与吉西他滨：合成，生物物理性质和生物学评估治疗胰腺癌。

用于治疗胰腺导管腺癌的一线化疗药物是吉西他滨。不幸的是，它的有效性由于其在肿瘤微环境中的耐化学性，低血管生成和药物生物分布限制而受到阻碍。必须开发新型的纳米疗法，以改善胰腺癌患者的预后。我们开发了一种合成方法，用于与[60]富勒烯-甘氨酸衍生物的水溶性纳米缀合物与FDA批准的药物吉西他滨（nanoC60GEM）。拟议的合成方案能够获得高度水溶性的[60]富勒烯-甘氨酸衍生物（6），然后使用EDCI / NHS碳二亚胺方案将其与吉西他滨成功偶联。使用质谱法和DLS，IR和XPS技术表征所需的纳米共轭物。通过测量1O2在1270 nm处的近红外发光，然后通过EPR光谱自旋捕获DMPO加合物，研究了单线态氧和超氧阴离子自由基的光生作用。进行的生物学分析表明，nanoC60GEM可抑制S期细胞周期并诱导细胞凋亡。在本文中，我们提出了一种健壮的方法与吉西他滨合成高度水溶性的[60]富勒烯纳米共轭物。在胰腺癌细胞系上进行的生物学分析证明了nanoC60GEM的细胞毒性作用，在合成的富勒烯纳米材料的蓝色LED照射后，活性氧的产生增强了nanoC60GEM的细胞毒性作用。