Glycopolymers Made from Polyrotaxanes Terminated with Bile Acids: Preparation, Self‐Assembly, and Targeting Delivery

Abstract

The use of natural compounds to construct biomaterials, including delivery system, is an attractive strategy. In the present study, through threading functional α‐cyclodextrins onto the conjugated macromolecules of poly(ethylene glycol) (PEG) and natural compound bile acid, glycopolymers of polyrotaxanes with the active targeting ability are obtained. These glycopolymers self‐assemble into micelles as evidenced by dynamic light scattering and transmission electron microscopy, in which glucosamine, as an example of targeting groups, is introduced. These micelles after loading doxorubicin (DOX) exhibit the selective recognition with cancer cells 4T1. Meanwhile, the maximal half inhibitory concentration is determined to be ≈2.5 mg L−1 for the DOX‐loaded micelles, close to the value of free DOX·HCl (1.9 mg L−1). The cumulative release of DOX at pH 5.5 is faster than at pH 7.4, which may be used as the controlled release system. This drug delivery system assembled by glycopolymers features high drug loading of DOX, superior biocompatibility. The strategy not only utilizes the micellization induced by bile acids, but also overcomes the major limitation of PEG such as the lack of targeting groups. In particular, this drug delivery platform can extend to grafting the other targeting groups, rendering this system more versatile.

Mechanical and Optical Properties of Reinforced Collagen Membranes for Corneal Regeneration through Polyrotaxane Cross-Linking

“…The PEG-dicarbonate was fabricated as previously described, followed by threading α-CD on this chain to get PPR (Scheme ), and the number of α-CDs on each PEG chain was estimated to be ca. 10 based on the integration ratio of peak “a” of α-CDs to peak “g” or “h” from dicarbonate on the 1 H nuclear magnetic resonance (NMR) spectrum (Figure A) . PPR was successfully end-capped by ADA, as evidenced by the 1 H NMR spectrum shown in Figure B, where the peaks “1”, “2”, and “3” of ADA were observed and the peaks “g” and “h” disappeared.…”

Cyclodextrin-Based Functional Glyconanomaterials

“…The primary positions of the αCD beads were next succinylated and the resulting interlocked poly(carboxylic acid) was subsequently conjugated with glucosamine. The glyco-αCD/PEG polyrotaxane thus obtained formed micelles in aqueous solution that exhibited remarkable doxorubicin-loading capabilities and selectively delivered the drug to mouse 4T1 breast cancer cells and not to normal NIH3T3 cells [76] (Figure 10). Jia, Ren and coworkers reported an alternative post-functionalization strategy for glycopolyrotaxane synthesis, whereby αCD was first threaded onto p-nitrophenyl carbonate-ended PEG chains followed by amide-forming capping with an amine-equipped bile acid derivative.…”

“…The primary positions of the αCD beads were next succinylated and the resulting interlocked poly(carboxylic acid) was subsequently conjugated with glucosamine. The glyco-αCD/PEG polyrotaxane thus obtained formed micelles in aqueous solution that exhibited remarkable doxorubicin-loading capabilities and selectively delivered the drug to mouse 4T1 breast cancer cells and not to normal NIH3T3 cells [76] (Figure 10). CD derivatives bearing substituents that fit the cyclooligosaccharide cavity can undergo self-inclusion or intermolecular inclusion phenomena.…”

“…A representative transmission electron microscopy (TEM) micrograph of the later is also shown. Adapted with permission from Reference [76]. Copyright 2019 WILEY-VCH.…”

“…Polyrotaxane-based glycopolymers developed by Jia, Ren and coworkers[76] and a schematic representation of their self-assembly into doxorubicin-loaded micelles for the targeted delivery of the drug to tumor cells. A representative transmission electron microscopy (TEM) micrograph of the later is also shown.…”