Supramolecular and Biomimetic Polypseudorotaxane/Glycopolymer Biohybrids:  Synthesis, Glucose-Surfaced Nanoparticles, and Recognition with Lectin

Abstract

A new class of supramolecular and biomimetic glycopolymer/poly(epsilon-caprolactone)-based polypseudorotaxane/glycopolymer triblock copolymers (poly(D-gluconamidoethyl methacrylate)-PPR-poly(D-gluconamidoethyl methacrylate), PGAMA-PPR-PGAMA), exhibiting controlled molecular weights and low polydispersities, was synthesized by the combination of ring-opening polymerization of epsilon-caprolactone, supramolecular inclusion reaction, and direct atom transfer radical polymerization (ATRP) of unprotected D-gluconamidoethyl methacrylate (GAMA) glycomonomer. The PPR macroinitiator for ATRP was prepared by the inclusion complexation of biodegradable poly(epsilon-caprolactone) (PCL) with alpha-cyclodextrin (alpha-CD), in which the crystalline PCL segments were included into the hydrophobic alpha-CD cavities and their crystallization was completely suppressed. Moreover, the self-assembled aggregates from these triblock copolymers have a hydrophilic glycopolymer shell and an oligosaccharide threaded polypseudorotaxane core, which changed from spherical micelles to vesicles with the decreasing weight fraction of glycopolymer segments. Furthermore, it was demonstrated that these triblock copolymers had specific biomolecular recognition with concanavalin A (Con A) in comparison with bovine serum albumin (BSA). To the best of our knowledge, this is the first report that describes the synthesis of supramolecular and biomimetic polypseudorotaxane/glycopolymer biohybrids and the fabrication of glucose-shelled and oligosaccharide-threaded polypseudorotaxane-cored aggregates. This hopefully provides a platform for targeted drug delivery and for studying the biomolecular recognition between sugar and lectin.

Synthesis of glycopolymers and their multivalent recognitions with lectins

“…This includes: free-radical polymerization (FRP), 45,47,[49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64] living anionic polymerization, 65 ring-opening polymerization (ROP), 66,67 ringopening metathesis polymerization (ROMP), 44,68-74 and controlled/living free-radical polymerization (CLRP) which, encompasses nitroxide mediated controlled free-radical polymerization (NMP), 75-83 atom transfer radical polymerization (ATRP), [84][85][86][87][88][89][90][91][92][93] and reversible addition-fragmentation chain transfer (RAFT) polymerisation. 16,46,[94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111]<...>…”

“…The biomolecular recognition between the PGAMA block was tested with ConA, a lectin specific for binding glucose. 90 Extensive work was carried out by Haddleton and co-workers on the combination of click chemistry and ATRP to prepare glycopolymers. 118 Co-clicking of mannose and galactose based azides allowed the alteration of the epitope density, which was shown to influence the interaction with rat mannose-binding lectin (MBL).…”

“…89,90,117,119,120,135,157,158 Furthermore, in situ assembly during polymerizations could also result in nano-fibres and nano-spheres. 57,59 These complex architectures derived from glycopolymers may display much higher affinity towards binding lectins, since spherical and three dimensioned structures gave greater surface area for lectins to access their binding ligands.…”

“…Materials based on poly(e-caprolactone) can degrade in the biological system, which makes these glycopolymers very appealing for application in the biological system. 89,90 Thermo-responsive glycopolymer micelles were synthesized by Stenzel and co-workers by combining a glycopolymer blockobtained via thiol-ene click reaction -with PDEGMA, a polymer with a LCST of 29 C in aqueous solution. The micelle formation and the bioactivity was tested with ConA via turbidimetric assay analyzed using UV-vis spectroscopy and DLS.…”

Glyconanoparticles for Biomedical Applications

“…Illustration of doxorubicin-loaded glycopolymer coated nanoparticles with a degradable polypeptide core for anticancer targeted drug delivery [52]. glycomonomer [61]. The self-assembled nanoparticles had a hydrophilic glycopolymer shell and an oligosaccharide -CD-threaded polypseudorotaxane core, changing from spherical micelles to vesicles with the decreasing weight fraction of glycopolymer (Fig.…”