Biomimetic poly(methyl methacrylate)-based terpolymers: modulation of bacterial adhesion effect

Adherence of Staphylococcus aureus, responsible for major foreign body infections, was assessed onto functionalized poly(methyl methacrylate)-based terpolymers bearing sulfonate and carboxylate groups and onto poly(methyl methacrylate) as control. These terpolymers, have been synthesized by radical copolymerization of methyl methacrylate, methacrylic acid, and sodium styrene sulfonate by varying the ratio R = [COO(-)]/[COO(-) + SO(3)(-)] from 0 to 1 and keeping ionic monomer content between 7 and 18%. Adsorption of fibronectin onto poly(methyl methacrylate) was shown to dramatically promote bacterial adherence, whereas a strong inhibition of bacteria adherence was observed onto functionalized terpolymers containing both carboxylate and sulfonate groups. When terpolymers were predominantly functionalized by carboxylate groups, bacteria adherence was favored and reached values close to those obtained for poly(methyl methacrylate). These results have been related to the distribution of the anionic groups along the macromolecular chains, creating active sites responsible for specific interactions with fibronectin and inducing modifications of its conformation. The conformation of the adsorbed adhesive protein was then suggested to have an influence on the availability of its interaction sites to bacteria adhesins and therefore on modulation of bacteria adherence. Inhibition of Staphylococcus aureus adherence by functionalized poly(methyl methacrylate)-based terpolymers is of great interest in the field of biomedical implants and especially in the case of ophthalmic applications.     

Surface modification of silicone intraocular implants to inhibit cell proliferation

Photo-cross-linkable polymers bearing cinnamic, sulfonate, and carboxylate groups were synthesized by radical polymerization leading to randomly distributed copolymers. These polymers were used to coat silicone intraocular lenses in order to reduce posterior capsule opacification, also named "secondary cataract". We previously demonstrated that polymers containing both carboxylate and sulfonate groups inhibit cell proliferation, and formulations with the ratio R = COO-/(COO- + SO3-) equal to 0.64 provided the highest inhibitory effect. Ionic polymers with this formulation were synthesized to contain a monomer with pendant siloxane groups in order to get compatibility with the silicone matrix of the intraocular lenses. Anchorage of the ionic polymer at the surface of the silicone implant was achieved by a cycloaddition reaction of the photosensitive groups according to two options. These modified silicone surfaces grafted onto intraocular lenses were shown to inhibit cell proliferation to 60%.     

Partially quarternized amino functional poly(methacrylate) terpolymers: versatile drug permeability modifiers

Partially quarternized poly(methacrylate) terpolymers (Q-BBMCs) have been synthesized, based on the basic butylated methacrylate copolymer (BBMC/EUDRAGIT E), an excipient approved by the Food and Drug Administration (FDA) and to date mainly applied for tablet coatings. Via straightforward polymer modification reactions, a series of Q-BBMCs with quarternization degrees of 22%, 42%, and 65% has been prepared. Apical to basolateral transport across Caco-2 cell monolayers was investigated, employing the paracellular transported compounds trospium and mannitol. At pH 6.5 quarternization resulted in increased permeation enhancement up to 2.8-fold compared to BBMC, that is, up to 7.3-fold compared to control. Moreover, measurements of the transepithelial electrical resistance (TEER) revealed a special advantage of the quarternized poly(methacrylate) terpolymers with respect to the pH range, in which the polymers exhibit biological activity as permeation enhancers. Whereas at pH 6.5 TEER dropped within 30 min below 30% of the initial value for all polymers, at pH 7.4 this effect solely occurred for Q-BBMCs, meaning a significant extension of the pH range relevant for drug permeation. In a subsequent period of 6 h, also excellent recovery was observed.     

A synthetic polymer, poly(2-methacryloyloxyethyl phosphorylcholine-co-n-stearyl methacrylate), stimulates insulin release from RINm5F insulinoma cells

A water-soluble phospholipid-like polymer, poly(2-methacryloyloxyethyl phosphorylcholine-co-n-stearyl methacrylate) (PMC(18), average molecular weight = 4.3 x 10(4)), at a concentration (0.5-5 mg/ml) showing no inhibition of cell proliferation, stimulated insulin release from RINm5F rat insulinoma cells in a concentration- and time-related manner. But poly(2-methacryloyloxyethyl phosphorylcholine) and other synthetic phospholipid-like polymers failed to stimulate insulin release.     

Synthesis of biocompatible PEG-Based star polymers with cationic and degradable core for siRNA delivery

Star polymers with poly(ethylene glycol) (PEG) arms and a degradable cationic core were synthesized by the atom transfer radical copolymerization (ATRP) of poly(ethylene glycol) methyl ether methacrylate macromonomer (PEGMA), 2-(dimethylamino)ethyl methacrylate (DMAEMA), and a disulfide dimethacrylate (cross-linker, SS) via an "arm-first" approach. The star polymers had a diameter ~15 nm and were degraded under redox conditions by glutathione treatment into individual polymeric chains due to cleavage of the disulfide cross-linker, as confirmed by dynamic light scattering. The star polymers were cultured with mouse calvarial preosteoblast-like cells, embryonic day 1, subclone 4 (MC3T3-E1.4) to determine biocompatibility. Data suggest star polymers were biocompatible, with ≥ 80% cell viability after 48 h of incubation even at high concentration (800 μg/mL). Zeta potential values varied with N/P ratio confirming complexation with siRNA. Successful cellular uptake of the star polymers in MC3T3-E1.4 cells was observed by confocal microscopy and flow cytometry after 24 h of incubation.     

One-pot regioselective synthesis of tetrahydroindazolones and evaluation of their antiproliferative and Src kinase inhibitory activities

A number of 2-substituted tetrahydroindazolones were synthesized by three-component condensation reaction of 1,3-diketones, substituted hydrazines, benzaldehydes, and Yb(OTf)(3) as a catalyst in [bmim][BF(4)] ionic liquid using a simple, efficient, and economical one-pot method. The synthesized tetrahydroindazolones were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), human ovarian adenocarcinoma (SK-OV-3), and c-Src kinase activity. 3,4-Dichlorophenyl tetrahydroindazolone derivative (15) inhibited the cell proliferation of HT-29 and SK-OV-3 cells by 62% and 58%, respectively. 2,3-Diphenylsubstituted tetrahydroindazolone derivatives, inhibited the cell proliferation of HT-29 cells by 65-72% at a concentration of 50 μM. In general, the tetrahydroindazolones showed modest inhibition of c-Src kinase where 4-tertbutylphenyl- and 3,4-dichlorophenyl- derivatives showed the inhibition of c-Src kinase with IC(50) values of 35.1 and 50.7 μM, respectively.     

Preparation and copolymerization of a novel carbohydrate containing monomer

A novel carbohydrate containing monomer was prepared by simple reaction of 2-vinyl-4,4′-dimethylazlactone (VDMA) and 1,2;5,6-diisopropylidene--d-glucofuranose (DAG). The monomer was easily homopolymerized as well as copolymerized with methyl methacrylate (MMA) to give high molecular weight polymers using free radical conditions. Upon removal of the isopropylidene groups from the polymer, water contact angles decreased for polymeric films of the material, indicating a more hydrophilic surface. The addition of a carbohydrate moiety to MMA copolymers increases its hydrophilicity and allows for potential use of the new polymer as a biomaterial in a variety of applications.     

Association behavior of biotinylated and non-biotinylated poly(ethylene oxide)-b-poly(2-(diethylamino)ethyl methacrylate)

Biotinylated and non-biotinylated copolymers of poly(ethylene oxide) (PEO) and poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) were synthesized by the atom transfer radical polymerization technique. The chemical compositions of the copolymers as determined by NMR are represented by PEO(113)PDEAEMA(70) and biotin-PEO(104)PDEAEMA(93), respectively. The aggregation behavior of these polymers in aqueous solutions at different pHs and ionic strengths was studied using a combination of potentiometric titration, dynamic light scattering, static light scattering, and transmission electron microscopy. Both PEO-b-PDEAEMA and biotin-PEO-b-PDEAEMA diblock copolymers form micelles at high pH with hydrodynamic radii (R(h)) of about 19 and 23 nm, respectively. At low pH, the copolymers are dispersed as unimers in solution with R(h) values of about 6-7 nm. However, at a physiological salt concentration (c(s)) of about 0.16 M NaCl and a pH of 7-8, the copolymers form large loosely packed Gaussian chains, which were not present at the low c(s) of 0.001 M NaCl. The critical micelle concentrations (cmc's) and the cytotoxicities of the copolymers were investigated to determine a suitable polymer concentration range for future biological applications. Both PEO-b-PDEAEMA and biotin-PEO-b-PDEAEMA diblock copolymers possess identical cmc values of about 0.0023 mg/g, while the cytotoxicity test indicated that the copolymers are not toxic up to 0.05 mg/g (>83% cell survival at this concentration).     

Selective cell attachment to a biomimetic polymer surface through the recognition of cell-surface tags

Reactive phosphorylcholine polymers, which can recognize biosynthetic cell-surface tags, were synthesized to control cell attachment. Human promyelocytic leukemia cells (HL-60) with unnatural carbohydrates as cell-surface tags were harvested by treatment with N-levulinoylmannosamine (ManLev). The attachment of ManLev-treated HL-60 cells to 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers with hydrazide groups was studied. HL-60 cells, which are nonadhesive, did not attach to any polymer surface without ManLev treatment. In contrast, ManLev-treated HL-60 cells attached to a poly[MPC-co-n-butyl methacrylate (BMA)-co-methacryloyl hydrazide (MH)] (PMBH) surface following 15 min of incubation. The cells that attached to the PMBH surface retained their native morphology and viability for 24 h of incubation. On the other hand, approximately half of the HL-60 cells that attached to the poly(BMA-co-MH) (PBH) surface died. These results suggest that MH units in the polymer act as anchors for cell attachment and MPC units help to preserve cell viability on a polymer surface. The coculture of ManLev-treated HL-60 and fluorescence-stained human uterine cervical cancer cells (HeLa) was carried out on polymer surfaces. ManLev-treated HL-60 cells specifically attached to the PMBH surface. In contrast, both HL-60 and HeLa cells were observed on the PBH surface. The control of cellular interactions with synthetic polymers may be useful for the future development of cell-integrated biosensors and biomedical devices.     

Cationic amphiphilic model networks based on symmetrical ABCBA pentablock terpolymers: synthesis, characterization, and modeling

Eight isomeric networks based on equimolar terpolymers were synthesized using group transfer polymerization (GTP) and were characterized in terms of their swelling properties. Two hydrophilic monomers, the nonionic methoxy hexa(ethylene glycol) methacrylate (HEGMA) and the ionizable 2-(dimethylamino)ethyl methacrylate (DMAEMA), and a hydrophobic (nonionic) monomer, methyl methacrylate (MMA), were employed for the syntheses. 1,4-Bis(methoxytrimethylsiloxymethylene)cyclohexane (MTSMC) was used as the bifunctional GTP initiator, while ethylene glycol dimethacrylate (EGDMA) served as the cross-linker. Seven of the networks were model networks, six of which were based on the symmetrical pentablock terpolymers ABCBA, ACBCA, BACAB, BCACB, CBABC, and CABAC, whereas the seventh model network was based on the statistical terpolymer. The eighth network was a randomly cross-linked network based on the statistical terpolymer, prepared by the simultaneous quaterpolymerization of the three monomers and the cross-linker. The molecular weights and molecular weight distributions of the linear pentablock terpolymer precursors, as well as those of their homopolymer and ABA triblock copolymer precursors, were characterized by gel permeation chromatography (GPC) in tetrahydrofuran. The sol fraction of each network was measured and found to be relatively low. The aqueous degrees of swelling of all networks were found to increase at acidic pH due to the ionization of the DMAEMA tertiary amine units. The acidic degrees of swelling of the pentablock terpolymer networks were lower than those of their statistical counterparts due to microphase separation in the former type of networks, also confirmed by thermodynamic calculations and small-angle neutron scattering experiments.     

Preparation of cholesteric (hydroxypropyl)cellulose/polymer networks and ion-mediated control of their optical properties

(Hydroxypropyl)cellulose (HPC)/vinyl polymer networks were synthesized in film form from liquid-crystalline solutions of HPC in a mixed solvent of methacrylate monomer/methanol/water (2:1:2 in weight) containing cross-linking agents, via photopolymerization of the methacrylate monomer. Di(ethylene glycol) monomethyl ether methacrylate (DEGMEM) or 2-hydroxypropyl methacrylate (HPMA) was used as the polymerizing monomer, and tetra(ethylene glycol) diacrylate and glutaraldehyde were the cross-linkers for the monomers and HPC, respectively. The polymer composite films, HPC/PDEGMEM and HPC/PHPMA, prepared at ca. 60-70 wt % concentrations of HPC in the starting solutions, were iridescently colored due to the selective light reflection, originating from the cholesteric helical arrangement carried over successively into the network system. When the cholesteric films were immersed and swollen in water containing an inorganic neutral salt, their coloration and optical turbidity varied according to a strength of 'chaotropicity' of the impregnant ions. This ionic effect may be interpreted as essentially identical with that found formerly in the coexistent salt-sort dependence of the cholesteric pitch and lower critical solution temperature for HPC aqueous solutions. It is also demonstrated that visual appearance of the swollen networks can be changed by application of an electric potential of practical magnitude between both edges of the samples of rectangular shape.     

Cell proliferation and cell sheet detachment from the positively and negatively charged nanocomposite hydrogels

The charged nanocomposite hydrogels (NC gels) were synthesized by copolymerization of positively or negatively chargeable monomer with N‐isopropylacrylamide (NIPAm) in the aqueous suspension of hectorite clay. The ionic NC gels preserved the thermo‐responsibility with the phase‐transition temperature below 37°C. The L929 cell proliferation was sensitive to charge polarity and charge density. As compared to the PNIPAm NC gel, the cationic NC gels with <5 mol % of 2‐(dimethylamino)ethyl methacrylate (DMAEMA) showed improved cell proliferation, whereas the cells grew slowly on the gels with negatively charged 2‐acrylamido‐2‐methylpropane sulfonic acid (AMPSNa). By lowering temperature, rapid cell sheet detachment was observed from the surface of ionic NC gels with 1 mol % of ionizable monomers. However, lager amount of AMPSNa or DMAEMA did not support rapid cell sheet detachment, probably owing to the adverse swelling effects and/or enhanced electrostatic attraction. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 58–65, 2014.     

Synthesis and hydration properties of pH-sensitive p(HEMA)-based hydrogels containing 3-(trimethoxysilyl)propyl methacrylate

An amphiphilic hydrogel network was synthesized from a cross-linked poly(2-hydroxyethyl methacrylate) backbone copolymerized with the monomers 3-(trimethoxysilyl)propyl methacrylate (PMA) and dimethylaminoethyl methacrylate (DMAEMA) using tetraethylene glycol diacrylate (TEGDA) as cross-linker and using the radical initiator system comprising N,N,N',N'-tetramethylethylenediamine and ammonium peroxydisulfate. The degree of hydration of hydrogel slabs was investigated as functions of varying monomer compositions and cross-link density and as a function of pH and ionic strength of the bathing medium. As much as a 45% increase in hydration was observed for hydrogels containing 15 mol % DMAEMA upon reducing the pH of the bathing medium from 8.0 to 2.0. This confirms the pH-modulated swelling of amine-containing hydrogels. Increasing the concentration of TEGDA cross-linker from 3 to 12 mol % in a 10 mol % DMAEMA-containing hydrogel resulted in only a 10% reduction in the degree of hydration of the gel. There was, however, a 40-50% reduction in the degree of hydration of a 15 mol % DMAEMA hydrogel upon increasing the molar composition of PMA from 0 up to 20 mol %. The presence of PMA confers hydrophobic character that reduces hydration and introduces additional cross-links that reduce network mesh size. The water content of the hydrogel was consistently higher in buffers of lower ionic strength. The reversible pH-dependent swelling observed in these studies, along with the control of cross-link density afforded by the PMA component, endows these biocompatible materials with potential for use in pH-controlled drug delivery of more hydrophobic drugs and present new compositions for in vitro and in vivo biocompatibility studies.     

Direct rapid synthesis of MIP beads in SPE cartridges

Selecting optimal compositions for non-covalent molecularly imprinted polymers (MIPs) and screening for appropriate rebinding conditions necessitates synthesising a large number of polymers. This is extremely labour-intensive and usually results in very limited "optimisation" in studies of MIPs. Here, a new method is proposed for rapid synthesis of MIPs in a beaded form that can be used directly in many different performance evaluation studies. The method is based on synthesis of spherical particles by suspension polymerisation in liquid fluorocarbon [Mayes, A., Mosbach, K., 1996. Molecularly imprinted polymer beads: suspension polymerisation using a liquid perfluorocarbon as the dispersing phase. Anal. Chem. 68, 3769-3774]. The polymers were directly polymerised under UV light in solid phase extraction (SPE) cartridges, then washed and extracted in the same cartridges where they had been synthesised, resulting in a rapid and automatable process that requires no transfer or manipulation of the polymer particles. The particles were similar in terms of size, morphology and functional performance to particles obtained by suspension polymerisation in fluorocarbon solvent using a conventional reactor. In this initial study, 36 polymers were synthesised to study the effect of a variation in the type and amount of four different functional monomers, methacrylic acid (MAA), acrylic acid (AA), hydroxyethyl methacrylate (HEMA) and 2-vinylpyridine (2-VPy), for the imprinting of propranolol and morphine. The performance of polymers synthesised using MAA was as expected, but those synthesised with AA as functional monomer showed more surprising rebinding properties as a function of monomer to cross-linker ratios, demonstrating the potential value of pragmatic synthesis and screening approaches to polymer optimisation.     

Mechanism of polymer-induced hemolysis: nanosized pore formation and osmotic lysis

Hemolysis induced by antimicrobial polymers was examined to gain an understanding of the mechanism of polymer toxicity to human cells. A series of cationic amphiphilic methacrylate random copolymers containing primary ammonium groups as the cationic functionality and either butyl or methyl groups as hydrophobic side chains have been prepared by radical copolymerization. Polymers with 0-47 mol % methyl groups in the side chains, relative to the total number of monomeric units, showed antimicrobial activity but no hemolysis. The polymers with 65 mol % methyl groups or 27 mol % butyl groups displayed both antimicrobial and hemolytic activity. These polymers induced leakage of the fluorescent dye calcein trapped in human red blood cells (RBCs), exhibiting the same dose-response curves as for hemoglobin leakage. The percentage of disappeared RBCs after hemolysis increased in direct proportion to the hemolysis percentage, indicating complete release of hemoglobin from fractions of RBCs (all-or-none leakage) rather than partial release from all cells (graded leakage). An osmoprotection assay using poly(ethylene glycol)s (PEGs) as osmolytes indicated that the PEGs with MW > 600 provided protection against hemolysis while low molecular weight PEGs and sucrose had no significant effect on the hemolytic activity of polymers. Accordingly, we propose the mechanism of polymer-induced hemolysis is that the polymers produce nanosized pores in the cell membranes of RBCs, causing an influx of small solutes into the cells and leading to colloid-osmotic lysis.     

Lipase-catalyzed synthesis of aliphatic polyesters via copolymerization of lactone, dialkyl diester, and diol

Candida antarctica lipase (CALB) has been successfully used as catalyst for copolymerization of dialkyl diester with diol and lactone to form aliphatic polyesters. The polymerization reactions were performed using a two stage process: first stage oligomerization under low vacuum followed by second stage polymerization under high vacuum. Use of the two-stage process is required to obtain products with high molecular weights at high yields for the following reasons: (i) the first stage reaction ensures that the monomer loss via evaporation is minimized to maintain 1:1 diester to diol stoichiometric ratio, and the monomers are converted to nonvolatile oligomers; (ii) use of high vacuum during the second stage accelerates equilibrium transesterification reactions to transform the oligomers to high molecular weight polymers. Thus, terpolymers of omega-pentadecalactone (PDL), diethyl succinate (DES), and 1,4-butanediol (BD) with a M w of whole product (nonfractionated) up to 77000 and M w/ M n between 1.7 and 4.0 were synthesized in high yields (e.g., 95% isolated yield). A desirable reaction temperature for the copolymerizations was found to be around 95 degrees C. At 1:1:1 PDL/DES/BD monomer molar ratio, the resultant terpolymers contained equal moles of PDL, succinate, and butylene repeat units in the polymer chains. (1)H and (13)C NMR analyses were used to determine the polyester microstructures. The synthesized PDL-DES-BD terpolymers possessed near random structures with all possible combinations of PDL, succinate, and butylene units via ester linkages in the polymer backbone. Furthermore, thermal stability and crystallinity of a pure PDL-DES-BD terpolymer with 1:1:1 PDL to succinate to butylene unit ratio and M w of 85400 were studied by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The copolyester was found to be a semicrystalline material with a T g of -34 degrees C and a T m of 64 degrees C, which degrades in a single weight loss step centered at T max = 408 degrees C.     

Characteristics of filamentous cells immobilized with ionic-hydrophobic polymers prepared by a radiation polymerization method

Filamentous cells of Trichoderma reesei were immobilized using a fibrous carrier covered with ionic-hydrophobic polymers, prepared by radiation copolymerization. The effect of the ionic properties of the polymers was investigated by changing the monomer composition in a trimethylpropane triacrylate (A-TMPT) — acrylic acid (AA) or methacrylic acid diethylaminoethyl ester (DEAEMA) system. More positive charge or less negative charge in the polymers led to an increase in the growth of the cells immobilized on their surface. Enzyme productivity in the immobilized cells with AA-A-TMPT polymer was higher than with a DEAEMA-A-TMPT polymer.     

Hemocompatibility of hydrophilic antimicrobial copolymers of alkylated 4-vinylpyridine

Quaternized poly(vinylpyridine) (PVP) is a polymer with inherent antimicrobial properties that is effective against Gram-positive bacteria, Gram-negative bacteria, viruses, and yeast cells. However, quaternized PVP has poor biocompatibility, which prevents its use in biomaterial applications. Copolymerization was examined as a method of modifying the structure to incorporate biocompatibility. Polyethyleneglycol methyl ether methacrylate (PEGMA) and hydroxyethyl methacrylate (HEMA) are polymers generally known to be biocompatible and thus were chosen as comonomers. Random copolymers of 4-vinylpyridine and PEGMA or HEMA were synthesized via free radical polymerization and quaternized with bromohexane. Copolymer biocompatibility was characterized by interaction with human red blood cells to analyze hemolysis. Hemolysis of human red blood cells was conducted on insoluble films and on water-soluble polymers in a serial dilution study. Hemolysis results demonstrated that blood compatibility does not depend on PEG chain length in PEGMA incorporated copolymers. Results indicate a critical weight ratio of PEGMA to VP in copolymers separating the no-hemolysis regime from 100% hemolysis.     

Synthesis, characterization, and evaluation as transfection reagents of double-hydrophilic star copolymers: effect of star architecture

Five star polymers of the ionizable hydrophilic 2-(dimethylamino)ethyl methacrylate (DMAEMA) and the nonionic hydrophilic methoxy hexa(ethylene glycol) methacrylate (HEGMA) were prepared by group transfer polymerization (GTP) using ethylene glycol dimethacrylate (EGDMA) as coupling agent. In particular, four isomeric star copolymers, one heteroarm, two star block and one statistical star, with 90% mol DMAEMA and 10% mol HEGMA, plus one star homopolymer of DMAEMA with degrees of polymerization of the arms equal to 20 were synthesized. The polymers were characterized in terms of their molar masses (MMs) and compositions using gel permeation chromatography (GPC) and proton nuclear magnetic resonance (1H NMR) spectroscopy, respectively. The hydrodynamic diameters in water indicated some aggregation for all the star polymers except for the statistical copolymer star, while the pK values of the DMAEMA units were around 7 for all star polymers. All the star polymers were evaluated for their ability to transfect human cervical HeLa cancer cells with the modified plasmid pRLSV40 bearing the enhanced green fluorescent protein (EGFP) as the reporter gene. All four star copolymers showed decreased toxicity compared to that of the DMAEMA star homopolymer for the same amounts of star polymer tested. The star block copolymer with outer DMAEMA blocks exhibited the highest overall transfection efficiency, 11%, compared to that of all the star polymers examined in this study. This efficiency was the same as that of the commercially available transfection reagent SuperFect.     

Preparation of cellulose graft poly(methyl methacrylate) copolymers by atom transfer radical polymerization in an ionic liquid

Cellulose graft poly(methyl methacrylate) copolymers were prepared by atom transfer radical polymerization (ATRP) in an ionic liquid. Cellulose chloroacetate, as a macroinitiator, was first synthesized by direct acylation of cellulose with chloroacetyl chloride without any catalysts under mild conditions in an ionic liquid, 1-allyl-3-methylimidazolium chloride (BMIMCl). Then, the macroinitiator was used for the ATRP of MMA mediated by the CuBr and 2,2′-bipyridine (bpy) catalysis system. The copolymerization was carried out in BMIMCl without homopolymer byproduct. The polymers were easily separated from the catalyst when the ionic liquid was used as reaction medium. The grafting copolymers were characterized by means of ¹H NMR, AFM and GPC. The results showed that the obtained copolymers had grafted polymer chains with well-controlled molecular weight and polydispersity, and the polymerization was a “living/controlled” system. Further, through AFM observation, it was found that the cellulose graft copolymer in solution could aggregate and self-assembly into sphere-like polymeric structure.