Effect of gemcitabine and retinoic acid loaded PAMAM dendrimer-coated magnetic nanoparticles on pancreatic cancer and stellate cell lines

Date

2014-07-01

Author

Yalcin, Serap
Erkan, Mert
Unsoy, Gozde
Parsian, Maryam
Kleeff, Jorg
Gündüz, Ufuk

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Gemcitabine is an anticancer drug used in the treatment of different cancer types, including pancreatic ductal adenocarcinoma. The maximum tolerated dose in humans is restricted by its side effects on healty cells. Furthermore, the fibrotic stroma produced by the pancreatic stellate cells prevents effective delivery of chemotherapeutic agents providing a safe-haven for the cancer cells. This becomes more of a problem considering the short half-life of this drug. Magnetic nanoparticle-based targeted drug delivery systems are a promising alternative to overcome the limitations of classical chemotherapies. The aim of this study is to obtain an effective targeted delivery system for gemcitabine using magnetic nanoparticles (MNPs) and all-trans retinoic acid (ATRA). This dual approach targets the tumor cells and its infrastructure - stellate cells - simultaneously. Gemcitabine and ATRA were loaded onto the PAMAM dendrimer-coated magnetic nanoparticles (DcMNPs), which were synthesized and characterized previously. Drug loading and release characteristics, and stability of the nanoparticles were investigated. Gemcitabine and ATRA loaded MNPs are efficiently taken up by pancreatic cancer and stellate cells successfully targeting and eliminating both cells. Results of this study can provide new insights on pancreatic cancer therapy where tumor is seen as a system with its stroma insead of epithelial cells alone. (C) 2014 Elsevier Masson SAS. All rights reserved.

Subject Keywords

Gemcitabine, Retinoic acid, PAMAM dendrimer, Nanoparticle, Pancreatic cancer, Stellate cell lines, Stellate cell lines

URI

https://hdl.handle.net/11511/30467

Journal

BIOMEDICINE & PHARMACOTHERAPY

DOI

https://doi.org/10.1016/j.biopha.2014.07.003

Collections

Graduate School of Natural and Applied Sciences, Article

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Citation Formats

S. Yalcin, M. Erkan, G. Unsoy, M. Parsian, J. Kleeff, and U. Gündüz, “Effect of gemcitabine and retinoic acid loaded PAMAM dendrimer-coated magnetic nanoparticles on pancreatic cancer and stellate cell lines,” BIOMEDICINE & PHARMACOTHERAPY, pp. 737–743, 2014, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/30467.