This report describes a technique for fabricating dual-structured hierarchical surface topography on the surface of polydimethylsiloxane (PDMS) films through simply replicating prefabricated patterns and wrinkling PDMS films. To enhance the biocompatibility of PDMS films, we synthesize a biocompatible dopamine-glycopolymer, which is utilized to modify the chemical feature of the PDMS surface. Dopamine component in this copolymer is introduced for the formation of a carbohydrate layer on the surface of PDMS films because of its excellent adhesion. The carbohydrate component in this copolymer enhances the interactions between cells and PDMS films. We investigate the influence of the chemical and topographical surface properties of the extracellular matrix on fibroblast cell growth. The coupling of the dopamine-glycopolymer coating and hierarchical topography produces the best induction effect on the alignment of cells.Keywords: cell behaviors; dopamine; dual-structured hierarchical topography; glycopolymer; surface modification; wrinkle films;

Quantum dots (QDs) are promising materials in nanophotonics, biological imaging, and even quantum computing. Precise positioning and patterning of QDs is a prerequisite for realizing their actual applications. Contrary to the traditional two discrete steps of fabricating and positioning QDs, herein, a novel sugar-electron-beam writing (SEW) method is reported for producing QDs via electron-beam lithography (EBL) that uses a carefully chosen synthetic resist, poly(2-(methacrylamido)glucopyranose) (PMAG). Carbon QDs (CQDs) could be fabricated in situ through electron beam exposure, and the nanoscale position and luminescence intensity of the produced CQDs could be precisely controlled without the assistance of any other fluorescent matter. We have demonstrated that upon combining an electron beam with a glycopolymer, in situ production of CQDs occurs at the electron beam spot center with nanoscale precision at any place and with any patterns, an advancement that we believe will stimulate innovations in future applications.

In this paper, novel star glycopolymers were synthesized via Cu(0)-mediated radical polymerisation at ambient temperature. The reaction was fast with little star–star coupling. Moreover, star glycopolymers can be obtained without removing oxygen from the polymerisation mixture. The effects of solvent and the ratio of initiator/catalyst/ligand on polymerisation were investigated, and the optimal conditions for the synthesis of star glycopolymer were determined. In addition, the binding ability between synthesised glycopolymers and concanavalin A (ConA) was studied using a turbidity test and quartz crystal microbalance-dissipation (QCM-D). Compared with linear glycopolymers, star glycopolymers showed higher binding ability to specific lectins and the strongest binding was obtained when the molecular weight was medium.

The successful sunlight-photolyzed reversible addition–fragmentation chain transfer (RAFT) photopolymerization can be reversibly activated and deactivated by irradiation with sunlight in the absence of photocatalyst and photoinitiator. In the present work, the thiocarbonylthio compounds (dithiobenzoate, trithiocarbonate, and xanthate) can all be employed to carry out the polymerization under sunlight irradiation acting as an initiator, chain transfer agent, and termination agent. Moreover, it was demonstrated that the recyclable-catalyst-aided, opened-to-air, and sunlight-photolyzed RAFT (ROS-RAFT) polymerizations can be successfully carried out to fabricate precise and predictable polymers in the presence of the recyclable magnetic semiconductor nanoparticles (NPs). The oxygen tolerance is likely attributed to a specific interaction between NPs and oxygen.

Novel and well-controlled copolymers, PDMA-co-PDMAEMA with bio-inspired dopamine-containing segments and electropositive PDMAEMA segments, PMAG-b-PMAA consisting of bio-targeted glucose-containing segments and electronegative PMAA segments, and a carboxyl-ending PMAG homopolymer, were synthesized and investigated by a combination of NMR, GPC, DLS and zeta potential measurements. After self-assembling the dopamine-containing polymer with Zn phthalocyanine (ZnPc) and decorating it with the sugar polymer PMAG-b-PMAA, the final nanoparticles presented better serum-stability and singlet oxygen quantum yields. More importantly, the in vitro and in vivo PDT experiments indicated that the pre-designed photoactive nanoparticles can well inhibit the growth of tumor cells.

Glyco-nanogels are glycopolymer-decorated nanoparticles of three-dimensional cross-linked networks, which have attracted ever-increasing interest of the biomedical-related community. However, most of the current reported glycosylated nanogels are prepared by copolymerization of glycopolymers with co-monomers and cross-linkers. Physically self-assembled glyco-nanogels remain a big challenge and are rarely explored. Herein, we report a new synthesis of glycosylated polyelectrolyte nanogels (glyco/CS nanogels), which are self-assembled from glycopolymers (PMAG-b-PMAA) synthesized through reversible addition–fragmentation chain transfer polymerization (RAFT) and quaternary ammonium chitosan (QACS) via electrostatic interactions under physiological conditions (pH 7.4, NaCl 0.15 M). The resultant glyco-nanogels have been demonstrated to be very stable in 10 mM HEPES buffer solution at least for 7 days and possess a specific binding capability to Con A. Their structure composed of an ionically cross-linked core and a glucose corona was confirmed by TEM. Compared with normal cells, glyco/CS nanogels exhibited a much higher affinity and cytotoxicity towards K562 cancer cells. In addition, the cellular uptake of these nanogels by K562 was further imaged via fluorescent microscopy in which nanogels with yellow-green signals were found to eventually co-locate within the cell nuclei of K562. The incorporation of natural and synthetic sugar polymers into polyelectrolytes has provided an insight to easily prepare glyco-nanogels with excellent colloidal stability, specific bioactivities and imaging ability, suggesting their great potential for biomedical applications.

Synthetic glycopolymers with pendent sugar moieties are able to interact with lectins as multivalent ligands in a similar manner to natural glycoproteins. Nanoparticles (NPs), due to their small size and high surface/volume ratio, lead to very different properties compared with bulk-matter, and NPs have shown great potential in nanomedicine and other biological applications. NPs with glycopolymers on the surface are one of the desirable bio-active particles and an important material to investigate. This review focuses on the synthesis of various glycopolymer-based nanoparticles via different approaches such as self-assembly and the preparation of glycopolymer-conjugated inorganic NPs, and their different applications.

Photodynamic therapy (PDT) is a promising singlet oxygen (1O2) mediated clinical treatment for many tumors. As the source of 1O2, oxygen plays an important role in the curative effect of PDT. However, the facts of photochemical depletion of oxygen and the intrinsic hypoxic microenvironment of tumors remain the major challenges. In this work, a novel photosensitizer carrier with oxygen self-compensating ability was designed for PDT. It was synthesized via chemical conjugation of hemoglobin (Hb) to polymeric micelles formed by triblock copolymers of poly(ethylene glycol)-block-poly(acrylic acid)-block-polystyrene (PEG-b-PAA-b-PS). The PEG-b-PAA-b-PS and resultant micelles in aqueous solution were comprehensively characterized by means of FTIR, 1H NMR, GPC, DLS, TEM, and fluorescence spectroscopy. The oxygen-binding capacity and antioxidative activity of the Hb conjugated micelles were evaluated via UV–vis spectroscopy. In addition, compared with the control micelles without Hb, the Hb conjugated photosensitizer carrier was able to generate more 1O2 and exert greater photocytotoxicity on Hela cells in vitro.

The protein binding capability of biomaterial surfaces can significantly affect subsequent biological responses, and appropriate ligand presentation is often required to guarantee the best functions. Herein, a new facile method for regulating this capability by varying the localized and average ligand density is presented. Binding between lysine and plasminogen relevant to a fibrinolysis system was chosen as a model. We integrated different lysine-modified β-cyclodextrin (β-CD) derivatives onto bioinert copolymer brushes via host–guest interactions. The localized and average lysine density can be conveniently modulated by changing the lysine valency on β-CD scaffolds and by diluting lysine-persubstituted β-CD with pure β-CD, respectively. Both the plasminogen adsorption and the plasminogen binding affinity were enhanced by lysine-persubstituted β-CD compared with those of lysine-monosubstituted β-CD, which is possibly due to the higher localized lysine density and the multivalent binding of plasminogen on lysine-persubstituted β-CD surfaces. With a change in the ratio of lysine-persubstituted β-CD to β-CD, the average lysine density can be tuned, leading to the linear regulation of the adsorption of plasminogen on surfaces.

Carbohydrates are involved in different cellular recognition events, and glycopolymers with carbohydrate side chains are currently being applied in many fields, with much potential for disease treatment. The aggregation shape has obvious effects on the nanoparticle–cell interaction and is therefore important for the applications of glycopolymers in biological systems. The synthesis of well-defined glyco-nanoparticles, especially non-spherical ones, is challenging work. Herein, iron oxide nanoparticles with different shapes (spindle and cubic-like) were first obtained and used as a core that was coated with dopamine methacrylamide (DMA) via catecholic chemistry for the introduction of vinyl groups. RAFT-synthesized glycopolymers were then conjugated to the DMA-coated iron oxide nanoparticles via a thiol–ene coupling reaction. By combining the convenience of inorganic nanoparticle shape control, biomimic catecholic chemistry, and efficient thiol–ene reaction, glycopolymer-decorated nanoparticles were easily obtained. Glyco-nanoparticles with variable shapes are stable in serum and exhibit shape-dependent cell uptake behaviors as well as enhanced activity toward specific lectins. The fabrication of biologically active non-spherical nanoparticles will be beneficial for both fundamental research on nanoparticle–cell interaction and related applications for disease treatment.

Side-chain functionalized glycopolymers have been successfully prepared in a well-controlled manner via a copper(0)-catalyzed one-pot reaction combining living radical polymerisation and ‘click chemistry’. The polymerisation was confirmed by the first-order kinetic plots, the linear relationships between molecular weights and the monomer conversions while keeping relatively narrow polydispersity (<1.33). The click conversion and polymerisation conversion versus reaction time plots for a Cu(0)-catalyzed one-pot reaction elucidate that the rates of click reaction are significantly faster than the polymerisation rates. Modified gold nanorods (GNRs) with glycopolymeric coatings were prepared through the interaction of Au–S bonds and the glycopolymer substituted GNRs showed strong, specific molecular recognition abilities with lectin (PNA).

A novel, highly efficient methodology to synthesize gradient glycopolymers has been successfully developed involving concurrent enzymatic monomer transformation and reversible addition–fragmentation chain transfer (RAFT) polymerization. By synchronizing enzymatic monomer transformation with polymerization, a continuous supply of the second monomer (glycomonomer) is achieved during the polymerization, resulting in a gradient sugar distribution in the final polymer. Detailed studies of the process using GPC and NMR indicate that the gradient glycopolymers synthesized by RAFT were well controlled. Subsequently, 1,2:3,4-di-O-isopropylidene-6-O-methacryloyl-α-d-galactopyranose (DIMAG) moieties were deprotected to regenerate the sugar and achieve amphiphilic bioactive glycopolymers. We demonstrate the synthesis of a set of glycopolymers with different sequential structures, such as statistical, gradient and block glycopolymers. The glycopolymers with block structure show higher affinities toward the RCA120 lectin receptor compared with other structural counterparts. Furthermore, simulation of the self-assembly of three types of copolymers and their binding to lectins provides fundamental insight into this result, revealing the mechanisms underlying the dependence of self-assembling structures and protein adsorption kinetics on the molecular architectures of copolymers.

•Patterning of silk fibroin films.•The influence of topography on HUVEC cell behavior.•HUVEC cells are aligned by topographic grooves and ridges.•The primary growth direction of filopodia is altered by pattern ridges.Silk fibroin is an ideal blood vessel substitute due to its advantageous qualities including variable size, good suture retention, low thrombogenicity, non-toxicity, non-immunogenicity, biocompatibility, and controllable biodegradation. In this study, silk fibroin films with a variety of surface patterns (e.g. square wells, round wells plus square pillars, square pillars, and gratings) were prepared for in vitro characterization of human umbilical vein endothelial cell's (HUVEC) response. The affects of biomimetic length-scale topographic cues on the cell orientation/elongation, proliferation, and cell-substrate interactions have been investigated. The density of cells is significantly decreased in response to the grating patterns (70 ± 3 nm depth, 600 ± 8 nm pitch) and the square pillars (333 ± 42 nm gap). Most notably, we observed the contact guidance response of filopodia of cells cultured on the surface of round wells plus square pillars. Overall, our data demonstrates that the patterned silk fibroin films have an impact on the behaviors of human umbilical vein endothelial cells.

•A method to design pH-sensitive chitosan-based polyelectrolyte nanogels is reported.•The charge-reversible property of polyanion relies on its hydrolysis in acidic media.•The formation of nanogels depends on MW of polyelectrolytes and titration order.•Nanogels disintegrate rapidly in an hour at pH 5.0 but are stable at pH 7.4.•The disintegration behavior of nanogels is consistent with polyanion's hydrolysis.A novel approach to design pH-sensitive and disintegrable polyelectrolyte nanogels composed of citraconic-based N-(carboxyacyl) chitosan (polyanion) and quaternary chitosan (polycation) was reported. Firstly, the hydrolysis of citraconic-modified chitosan was monitored using fluorescamine assay and it could selectively dissociate in acidic media (e.g., pH ∼5.0) due to the isomerization during the addition of citraconic anhydride to chitosan. Secondly, the self-assembly behaviors of different polyelectrolyte pairs between citraconic-based chitosan and quaternary chitosan were investigated via colloidal titration assay. It was indicated that the difference in molecular weight (MW) of opposite charged polyelectrolytes played an important role on the formation of polyelectrolyte nanogels. Results showed that polyelectrolyte nanogels (ca. 300 nm in size) only formed when polyanion and polycation had a very large difference in MW. The pH-sensitive behavior of polyelectrolyte nanogels was comprehensively investigated by dynamic light scattering (DLS) and transmission electron microscope (TEM). The incorporation of charge-conversional citraconic-based chitosan into polyelectrolyte complexes has provided an effective approach to prepare polyelectrolyte nanogels which were very stable at neutral pH but disintegrated quickly in acidic media.

A novel multi-targeting nanocarrier (SiPc-polymer) for photodynamic therapy (PDT) has been successfully polymerized via the incorporation of silicon(IV) phthalocyanine dichloride (SiPcCl2) to the thermoresponsive PEG-methacrylates based polymers. The resulting SiPc-polymer was characterized by 1H NMR spectroscopy, GPC, UV-Vis and elemental analysis. The lower critical solution temperature (LCST) of the SiPc-polymer can be easily controlled via changing the ratio of the applied monomers, di(ethylene glycol) methyl ether methacrylate (DEGMEMA), oligo(ethylene glycol) methyl ether methacrylate (OEGMEMA, Mw = 475 g mol−1) and 2-hydroxyethyl methacrylate (HEMA). The synthesized polymers assemble into nanoparticles (70 nm) in aqueous solution, which normally exhibits permeation and retention (EPR) effects, the thermo-responsive features provide the possibility to selectively accumulate at a maligned tissue site upon mild heating and high singlet oxygen quantum yields (ΦΔ = 0.55) are obtained which guarantee the controlled liberation of reactive oxygen species upon light irradiation. This provides a simple way to synthesize a multi-targeting drug carrier system for PDT.

Surface-initiated SET-LRP was used to synthesize polymer brush containing N-isopropylacrylamide and adamantyl acrylate using Cu(I)Cl/Me6-TREN as precursor catalyst and isopropanol/H2O as solvent. Different reaction conditions were explored to investigate the influence of different parameters (reaction time, catalyst concentration, monomer concentration) on the polymerization. Copolymers with variable 1-adamantan-1-ylmethyl acrylate (Ada) content and comparable thickness were synthesized onto silicon surfaces. Furthermore, the hydrophilic and bioactive molecule β-cyclodextrin-(mannose)7 (CDm) was synthesized and complexed with adamantane via host–guest interaction. The effect of adamantane alone and the effect of CDm together with adamantane on the wettability and thermoresponsive property of surface were investigated in detail. Experimental and molecular structure analysis showed that Ada at certain content together with CDm has the greatest impact on surface wettability. When Ada content was high (20%), copolymer–CDm surfaces showed almost no CDm complexed with Ada as the result of steric hindrance.

Carbohydrates are involved in different cellular recognition events, and glycopolymers with carbohydrate side chains are currently being applied in many fields, with much potential for disease treatment. The aggregation shape has obvious effects on the nanoparticle–cell interaction and is therefore important for the applications of glycopolymers in biological systems. The synthesis of well-defined glyco-nanoparticles, especially non-spherical ones, is challenging work. Herein, iron oxide nanoparticles with different shapes (spindle and cubic-like) were first obtained and used as a core that was coated with dopamine methacrylamide (DMA) via catecholic chemistry for the introduction of vinyl groups. RAFT-synthesized glycopolymers were then conjugated to the DMA-coated iron oxide nanoparticles via a thiol–ene coupling reaction. By combining the convenience of inorganic nanoparticle shape control, biomimic catecholic chemistry, and efficient thiol–ene reaction, glycopolymer-decorated nanoparticles were easily obtained. Glyco-nanoparticles with variable shapes are stable in serum and exhibit shape-dependent cell uptake behaviors as well as enhanced activity toward specific lectins. The fabrication of biologically active non-spherical nanoparticles will be beneficial for both fundamental research on nanoparticle–cell interaction and related applications for disease treatment.

Glyco-nanogels are glycopolymer-decorated nanoparticles of three-dimensional cross-linked networks, which have attracted ever-increasing interest of the biomedical-related community. However, most of the current reported glycosylated nanogels are prepared by copolymerization of glycopolymers with co-monomers and cross-linkers. Physically self-assembled glyco-nanogels remain a big challenge and are rarely explored. Herein, we report a new synthesis of glycosylated polyelectrolyte nanogels (glyco/CS nanogels), which are self-assembled from glycopolymers (PMAG-b-PMAA) synthesized through reversible addition–fragmentation chain transfer polymerization (RAFT) and quaternary ammonium chitosan (QACS) via electrostatic interactions under physiological conditions (pH 7.4, NaCl 0.15 M). The resultant glyco-nanogels have been demonstrated to be very stable in 10 mM HEPES buffer solution at least for 7 days and possess a specific binding capability to Con A. Their structure composed of an ionically cross-linked core and a glucose corona was confirmed by TEM. Compared with normal cells, glyco/CS nanogels exhibited a much higher affinity and cytotoxicity towards K562 cancer cells. In addition, the cellular uptake of these nanogels by K562 was further imaged via fluorescent microscopy in which nanogels with yellow-green signals were found to eventually co-locate within the cell nuclei of K562. The incorporation of natural and synthetic sugar polymers into polyelectrolytes has provided an insight to easily prepare glyco-nanogels with excellent colloidal stability, specific bioactivities and imaging ability, suggesting their great potential for biomedical applications.