Beta-cyclodextrin derivatives based macromolecular materials for biomedical applications and magnetic resonance imaging
Abstract
Polyrotaxanes are supramolecular molecular machines, that consist of self-assembly and inclusion complexation between CDs and polymers, have been extensively designed for biomedical applications such as drug delivery, non-viral gene delivery, and tissue engineering. Because of their non-covalent assembly characteristics, these supermolecules exhibit unique properties, including (i) the dynamically translational and rotational motions of the threaded cyclodextrin molecules along the polymer axles, (ii) their ability to completely dissociate into CD monomers and unthreaded polymer core after cleavage of the stoppers, properties that are never observed in other synthetic polymers, and (iii) a molecular structure that offers huge opportunities for to chemically tunable modifications. Thus, polyrotaxanes have attracted wide interest in supramolecular and polymer chemistry, with particular attention focused on their potential applications as sliding ring gels, molecular machines, and as carriers for drug and gene delivery. However, due to the poor water solubility and toxicity (i.e., nephrotoxicity) of those polyrotaxanes that have been developed with the native beta-cyclodextrin (β-CD), their utilization is limited. Herein, we have designed and developed families of β-CD derivatives and Pluronics based polyrotaxanes and demonstrated their versatile applications. These supramolecules, obtained from FDA-approved and biocompatible materials have shown excellent efficacy in removal of unesterified cholesterol accumulated in NPC2 -/- cells and decrease of liver and brain inflammation in NPC1 deficient mice. To address the solubility issue, mixture of water soluble β-CD derivatives such as 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and 4-sulfobutylether-β-cyclodextrin (SBE-β-CD) were threaded onto Pluronic copolymers. Using magnetic resonance imaging (MRI) modality, we demonstrated that these polyrotaxanes can be retained for a longer time in blood pool and can be utilized as potent MRI contrast agents.
Degree
Ph.D.
Advisors
Thompson, Purdue University.
Subject Area
Chemistry|Organic chemistry
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