Threaded macromolecules as a versatile framework for biomaterials

Abstract

Polyrotaxanes (PRXs) are a class of supramolecular threaded macromolecules, in which cyclic molecules are threaded onto the main- or side-chain of polymers. To date, various studies have been conducted on the synthesis of PRXs, and various combinations of cyclic molecules and polymers that can form a PRX have been discovered. Among these combinations, PRXs composed of cyclodextrins (CDs) and a linear polymer have attracted much attention and have been investigated by many researchers. Because of the non-covalently associated characteristic of PRXs, these supermolecules exhibit unique properties, such as the dynamic motion of the threaded cyclic molecules along a polymer axle and complete dissociation of the supramolecular structure, that are never observed in other synthetic polymers. These inherent properties of PRXs are of interest in the design of novel biomaterials, such as hydrogels, scaffolds in tissue engineering, drug delivery carriers, and polymer-drug conjugates. Thus, various studies have been conducted to utilize PRXs as a framework for biomaterials. In this review, we describe the recent progress in biomaterial application of PRXs such as drug delivery and gene delivery.

Versatile synthesis of end-reactive polyrotaxanes applicable to fabrication of supramolecular biomaterials

“…In addition to such fluorescent molecules, many functional molecules could be introduced at the terminal of the PRXs via copper-catalyzed or copper-free click reactions, including ligand molecules for active targeting, radioactive molecules for in vivo imaging, hydrophobic polymers for the surface immobilization of PRXs, and hydrophilic polymers for acquiring water solubility. Accordingly, the azide group-terminated end-reactive 4a and 4b are expected to be useful candidates in the fabrication or functionalization of supramolecular biomaterials, such as cross-linked hydrogels, surface immobilization, and drug delivery carriers for biomolecules [6]. Further studies relating to the biomaterials applications of azide group-terminated PRXs are currently underway in our laboratory and will be reported elsewhere.…”

“…Because the threading CDs are associated along the polymer chain via non-covalent intermolecular interactions, they can move freely along the polymer chain. This free mobility of threading CDs in PRXs is attractive for the development of functional supramolecular materials [4–6]. In PRX applications, chemical modification of the threading CDs is important to reduce intermolecular interactions of the PRXs, impart solubility in organic solvents and water, and introduce functional molecules [7–9].…”

A one-step synthesis of polyrotaxane via in situ Michael addition reaction

“…The threaded CDs are able to rotate and move along the guest linear chain freely [2]. This unique property is thought to give some outstanding advantages to PR materials [3][4][5].…”

Supramolecular Pharmaceutical Sciences: A Novel Concept Combining Pharmaceutical Sciences and Supramolecular Chemistry with a Focus on Cyclodextrin-Based Supermolecules

“…Tamura et al 32,[118][119][120][121] developed biodegradable polyrotaxanes including 2-(2-hydroxyethoxy) ethyl β-CyD (HEE-β-CyD) and demonstrated their therapeutic effects for NPC (Fig. 4).…”

“…29,30) Furthermore, various biomaterials and drug carriers based on CyD polyrotaxanes have been developed by many researchers. [31][32][33][34] Thus CyD-based mechanically interlocked molecules, especially polyrotaxanes, are very useful materials in various fields.…”