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Title: The endocytic pathway and therapeutic efficiency of doxorubicin conjugated cholesterol-derived polymers
Authors: Sevimli, Sema
Sagnella, Sharon
Macmillan, Alexander
Whan, Renee
Kavallaris, Maria
Bulmuş, Volga
Davis, Thomas P.
Keywords: Cells
Conjugated polymers
Therapeutic efficiency
Endocytic pathways
Issue Date: Feb-2015
Publisher: Royal Society of Chemistry
Source: Sevimli, S., Sagnella, S., Macmillan, A., Whan, R., Kavallaris, M., Bulmuş, V., and Davis, T. P. (2015). The endocytic pathway and therapeutic efficiency of doxorubicin conjugated cholesterol-derived polymers. Biomaterials Science, 3(2), 323-335. doi:10.1039/c4bm00224e
Abstract: Previously synthesized poly(methacrylic acid-co-cholesteryl methacrylate) P(MAA-co-CMA) copolymers were examined as potential drug delivery vehicles. P(MAA-co-CMA) copolymers were fluorescently labelled and imaged in SHEP and HepG2 cells. To understand their cell internalization pathway endocytic inhibition studies were conducted. It was concluded that P(MAA-co-CMA) are taken up by the cells via clathrin-independent endocytosis (CIE) (both caveolae mediated and cholesterol dependent endocytosis) mechanisms. The formation and characterization of P(MAA-co-CMA)-doxorubicin (DOX) nanocomplexes was investigated by fluorescence lifetime imaging microscopy (FLIM), UV-Visible spectroscopy (UV-Vis) and dynamic light scattering (DLS) studies. The toxicity screening between P(MAA-co-CMA)-DOX nanocomplexes (at varying w/w ratios) and free DOX, revealed nanocomplexes to exhibit higher cytotoxicity towards cancer cells in comparison to normal cells. FLIM and confocal microscopy were employed for investigating the time-dependent release of DOX in SHEP cells and the cellular uptake profile of P(MAA-co-CMA)-DOX nanocomplexes in cancer and normal cell lines, respectively. The endocytic pathway of P(MAA-co-CMA)-DOX nanocomplexes were examined in SHEP and HepG2 cells via flow cytometry revealing the complexes to be internalized through both clathrin-dependent (CDE) and CIE mechanisms. The drug delivery profile, reported herein, illuminates the specific endocytic route and therapeutic efficiency of P(MAA-co-CMA)-DOX nanocomplexes strongly suggesting these particles to be promising candidates for in vivo applications.
ISSN: 2047-4830
Appears in Collections:Chemical Engineering / Kimya Mühendisliği
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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