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Title: A [60]fullerene nanoconjugate with gemcitabine : synthesis, biophysical properties and biological evaluation for treating pancreatic cancer
Authors: Nalepa, Paweł
Gawecki, Robert
Szewczyk, Grzegorz
Balin, Katarzyna
Dulski, Mateusz
Sajewicz, Mieczysław
Mrozek-Wilczkiewicz, Anna
Musioł, Robert
Polański, Jarosław
Serda, Maciej
Keywords: [60]Fullerene; Nanoconjugate; Gemcitabine; Pancreatic cancer
Issue Date: 2020
Citation: Cancer Nanotechnology, 2020, iss. 11, art. no. 2
Abstract: Background: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.Results:We developed a synthetic methodology for obtaining a water‑soluble nano‑conjugate of a [60]fullerene‑glycine derivative with the FDA‑approved drug gemcit‑abine (nanoC60GEM). The proposed synthetic protocol enables a highly water‑soluble [60]fullerene‑glycine derivative (6) to be obtained, which was next successfully conju‑gated with gemcitabine using the EDCI/NHS carbodiimide protocol. The desired nano‑conjugate 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.Conclusion: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.
DOI: 10.1186/s12645-020-00058-4
ISSN: 1868-6966
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