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Abstract
Aim: Glycoconjugated C60 derivatives are of particular interest as potential cancer targeting agents due to an upregulated metabolic glucose demand, especially in the case of pancreatic adenocarcinoma and its dense stroma, which is known to be driven by a subset of pancreatic stellate cells. Materials & methods: Herein, we describe the synthesis and biological characterization of a hexakis-glucosamine C60 derivative (termed ‘Sweet-C60’). Results: Synthesized fullerene derivative predominantly accumulates in the nucleus of pancreatic stellate cells; is inherently nontoxic up to concentrations of 1 mg/ml; and is photoactive when illuminated with blue and green light, allowing its use as a photodynamic therapy agent. Conclusion: Obtained glycoconjugated nanoplatform is a promising nanotherapeutic for pancreatic cancer.
Graphical Abstract
Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/nnm-2018-0239
Acknowledgments
Our thanks are extended to R Hwang of the Department of Surgical Oncology, University of Texas MD Anderson Cancer who kindly provided the pancreatic stellate cells.
Financial & competing interests disclosure
M Serda, JM Newton, MJ Ware, S Sachdeva, M Krzykawska-Serda, J Law, L Nguyen, SA Curley and SJ Corr acknowledge the funding of Kanzius Foundation and NIH U54CA143837. LJ Wilson also thanks the Welch Foundation (grant number C-0627) for support. Additionally, M Serda thanks National Science Center (Poland) for the support (grant number UMO-2016/23/D/NZ7/00912). MJ Ware and SJ Corr acknowledge the support of St Luke's Foundation Philip Salem Award. JM Newton acknowledges financial support from the NIGMS T32 predoctoral training (grant number T32GM088129) and NIDCR F31 NRSA training grant (grant number F31DE026682) both of the NIH. This project was supported by the Cytometry and Cell Sorting Core at Baylor College of Medicine with funding from the NIH (grant numbers NIAID P30AI036211, NCI P30CA125123 and NCRR S10RR024574) and the assistance of JM Sederstrom. This content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors declare no conflicts of interest.
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical disclosure
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.
Author contributions
Conception and design: M Serda, MJ Ware, M Krzykawska-Serda, LJ Wilson, SJ Corr and SA Curley. Acquisition of data: M Serda, MJ Ware, M Krzykawska-Serda, JM Newton, S Sachdeva. Analysis and interpretation of the data: M Serda, MJ Ware, M Krzykawska-Serda, JM Newton, S Sachdeva, and SJ Corr. Manuscript preparation: M Serda, SJ Corr, MJ Ware, JM Newton and M Krzykawska-Serda wrote the manuscript. All authors read and approved the final manuscript.
Blinded for review
Methods and materials:
Cell culture: R. Hwang (UT-MD Anderson Cancer Center, Houston TX); The University of Texas M.D. Anderson Cancer Center; The Institutional Review Board of The University of Texas M.D. Anderson Cancer Center; The University of Texas M.D. Anderson Cancer Center.