Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/5245
Title: Well-defined cholesterol polymers with pH-controlled membrane switching activity
Authors: Sevimli, Sema
İnci, Fatih
Zareie, Hadi M.
Bulmuş, Volga
Keywords: Copolymers
Cell membranes
Cholesteryl methacrylate
Cholesterol
Ultraviolet visible spectroscopy
Switching activities
Issue Date: Oct-2012
Publisher: American Chemical Society
Source: Sevimli, S., İnci, F., Zareie, H. M., and Bulmuş, V. (2012). Well-defined cholesterol polymers with pH-controlled membrane switching activity. Biomacromolecules, 13(10), 3064-3075. doi:10.1021/bm300846e
Abstract: Cholesterol has been used as an effective component of therapeutic delivery systems because of its ability to cross cellular membranes. Considering this, well-defined copolymers of methacrylic acid and cholesteryl methacrylate, poly(methacrylic acid-co-cholesteryl methacrylate) P(MAA-co-CMA), were generated as potential delivery system components for pH-controlled intracellular delivery of therapeutics. Statistical copolymers with varying cholesterol contents (2, 4, and 8 mol %) were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Dynamic light scattering (DLS) analysis showed that the hydrodynamic diameters of the copolymers in aqueous solutions ranged from 5 ± 0.3 to 7 ± 0.4 nm for the copolymers having 2 and 4 mol % CMA and 8 ± 1.1 to 13 ± 1.9 nm for the copolymer having 8 mol % CMA with increasing pH (pH 4.5-7.4). Atomic force microscopy (AFM) analysis revealed that the copolymer having 8 mol % CMA formed supramolecular assemblies while the copolymers having 2 and 4 mol % CMA existed as unimers in aqueous solution. The pH-responsive behavior of the copolymers was investigated via UV-visible spectroscopy revealing phase transitions at pH 3.9 for 2 mol % CMA, pH 4.7 for 4 mol % CMA, and pH 5.4 for 8 mol % CMA. Lipid bilayers and liposomes as models for cellular membranes were generated to probe their interactions with the synthesized copolymers. The interactions were determined in a pH-dependent manner (at pH 5.0 and 7.4) using surface plasmon resonance (SPR) spectroscopy and liposome leakage assay. Both the SPR analyses and liposome leakage assays indicated that the copolymer containing 2 mol % CMA displayed the greatest polymer-lipid interactions at pH 5.0, presenting the highest binding ability to the lipid bilayer surfaces, and also demonstrating the highest membrane destabilization activity. CellTiter-Blue assay showed that the copolymers did not affect the cell viability up to 30 μM over a period of 72 h. © 2012 American Chemical Society.
URI: http://doi.org/10.1021/bm300846e
http://hdl.handle.net/11147/5245
ISSN: 1526-4602
1525-7797
Appears in Collections:Chemical Engineering / Kimya Mühendisliği
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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