Bio-inspired, multifunctional Block Copolymers to absorb Cholesterol and Calcium – Towards dissolution of Atherosclerotic Plaques

Coronary atherosclerosis and the related cardiovascular diseases constitute one of the most serious health problems in the Western Hemisphere, which causes around 40 % of all deaths.[1] Based on the high lethal number of... [ view full abstract ]

Coronary atherosclerosis and the related cardiovascular diseases constitute one of the most serious health problems in the Western Hemisphere, which causes around 40 % of all deaths.^[1] Based on the high lethal number of coronary diseases, we introduce a novel strategy (Figure 1). Plaque-sensitive macro-surfactants were synthesized to target arterial plaques, extract partially hydrophobic and ionic compounds, encapsulate them within stable aggregates and finally, excrete over the renal pathway. The plaque is very complexly composed of solid blood components, hydrophobic components like cholesterol, but also of inorganic deposits of calcium minerals.^[2],[3] The class of synthesized multifunctional triblock copolymers with covalently attached cholesteryl and anionic moieties is assumed to achieve interactions with hydrophobic and mineral parts of the arterial deposit. Moreover pendant polyethylene glycol increases the water solubility. Complementary analytical techniques (DLS, AUC, cryo-TEM, CMC fluorescence measurements and zeta-potential measurements) suggest the self-oriented arrangement of the polymers into distinct shaped, spherical particles in the lower nanometer range with a negatively charged surface. The polymeric dispersions (Figure 2) were able to dissolve and absorb solid cholesterol (up to 5.6 wt%) and calcium ions bound in mineral structures and entrap them within micellar nanoassemblies. Furthermore, ex-vivo alamar blue assays against human kidney epithelial cells negated toxic impacts of the polymers.

[1]            M. Nichols, N. Townsend, P. Scarborough, M. Rayner, European Heart Network and European Society of Cardiology 2012.

[2]            T. P. Wrobel, L. Mateuszuk, R. B. Kostogrys, S. Chlopicki, M. Baranska, The Analyst 2013, 138, 6645-6652.

[3]            S. Bertazzo, E. Gentleman, K. L. Cloyd, A. H. Chester, M. H. Yacoub, M. M. Stevens, Nat Mater 2013, 12, 576-583.