Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/5566
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
Cholesterol
Conjugated polymers
Therapeutic efficiency
Polyacrylates
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.
URI: http://doi.org/10.1039/c4bm00224e
http://hdl.handle.net/11147/5566
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

Files in This Item:
File Description SizeFormat 
5566.pdfMakale2.7 MBAdobe PDFThumbnail
View/Open
Show full item record

CORE Recommender

SCOPUSTM   
Citations

16
checked on Aug 10, 2022

WEB OF SCIENCETM
Citations

17
checked on Jun 21, 2022

Page view(s)

122
checked on Aug 8, 2022

Download(s)

156
checked on Aug 8, 2022

Google ScholarTM

Check

Altmetric


Items in GCRIS Repository are protected by copyright, with all rights reserved, unless otherwise indicated.