Multifunctional Block Copolymers for Simultaneous Solubilization of Poorly Water‐Soluble Cholesterol and Hydroxyapatite Crystals

Abstract

The solubilization of targeted compounds represents key criteria in the sophisticated field of medical chemistry but also in technical applications like scale removal. Especially, the simultaneous dissolution of two chemically different compounds remains challenging. Herein, macromolecular solubilizers are introduced for the simultaneous dissolution and encapsulation of poorly water-soluble cholesterol and hydroxyapatite. The peptide-based, amphiphilic block copolymers possess physicochemically disparate segments combined in one polymer chain as binding sites for hydrophobic as well as ionic materials. Small polymer libraries are synthesized and screened for structure-property relationships. Complementary analytical techniques suggest polymeric self-assembly into spherical adaptive nanoparticles with the fundamental ability to passively absorb significant amounts of hydrophobic cholesterol up to 33 wt%. Furthermore, the additional incorporation of acidic domains enables the simultaneous dissolution of hydrophobic compounds and mineral phases such as hydroxyapatite. Ultimately, those nontoxic block copolymers can be used to solubilize and absorb other lipophilic and ionic compounds such as Sudan III dye and calcium ions. Such multifunctional nanomaterials have a wide range of direct application for simultaneous dissolution or delivery of hydrophobic molecules and cations resp. minerals for instance in the field of atherosclerosis.

Visualizing Cholesterol Uptake by Self‐Assembling Rhodamine B‐Labeled Polymer Inside Living Cells via FLIM‐FRET Microscopy

“…The synthesis of the multifunctional triblock polymer mPEG‐b‐PGlu 12 ‐b‐PLys 11 (Chol) 1.5 was described previously . The polydispersity index (PDi) was determined to be 1.13 by gel permeation chromatography.…”

“…In order to evaluate this potential effect, dynamic light scattering (DLS) and zeta potential measurements of the RhoB polymer particles were performed. DLS revealed slight increases of both the average particle size (from 16 to 20 nm, number‐weighted sizes) and the polydispersities (from 0.251 to 0.312) due to the RhoB attachment (Figure S2, Supporting Information). This structural change might be induced by the micro‐environmental expansion in the particle core caused by the steric demand of the fluorescence tag.…”

“…The difference between the number‐ and the intensity‐weighted size distribution is discussed in detail in the Supporting Information (Figure S3, Supporting Information). In addition, zeta potential measurements indicate a minor decreased surface charge of the RhoB polymer particles (−13.2 mV) as compared to the native polymer particles (−13.0 mV) originating from the RhoB attachment to the lysine block and thus the effective reduction of positive charges at physiological pH (Figure S4, Supporting Information). Taken together, the structural analysis gives rise to the conclusion that the polymeric nanoparticles do not significantly change their structure after the RhoB modification.…”

“…The detailed synthesis and characterization was reported previously . In brief, α‐amino‐ω‐methoxy‐poly(ethylene glycol) (1.000 g, 0.2 mmol, M n = 5000 g mol −1 ) was dissolved in dimethyl formamide (8 mL) and added to a solution of γ‐benzyl glutamic acid‐ N ‐carboxyanhydride (BzGlu‐NCA, 0.632 g, 2.4 mmol, 12 equiv.)…”

“…In our laboratories, multifunctional polymers with binding sites for both cholesterol and calcium uptake have been developed. These biocompatible polymers self‐organize into nano‐sized polymeric particles, which simultaneously absorb significant quantities of cholesterol (4 wt%) and calcium ions dissolved from hydroxyapatite (0.17 Ca 2+ /COO − ) from solution . Hence, these polymers are a promising tool for treating atherosclerosis.…”