Biodegradable and thermosensitive micelles of amphiphilic polyaspartamide derivatives containing aromatic groups for drug delivery

The preparation, characterization, release, and in vitro cytotoxicity of a biodegradable polymeric micellar formulation of paclictaxel (PTX) were investigated. The micelles based on thermosensitive and degradable amphiphilic polyaspartamide derivatives containing pendant aromatic structures (phe‐g‐PHPA‐g‐mPEG) were prepared by a quick heating method without using toxic organic solvent. Dynamic light‐scattering results show that the micelles are stable upon dilution under physiological conditions and the destabilization of the micelles is pH‐dependent and the phe‐g‐PHPA‐g‐mPEG polymers are biodegradable. PTX was loaded into the phe‐g‐PHPAs‐g‐mPEG micelles with encapsulation efficiency of >90%, resulting in a high drug loading content (up to 29%). PTX‐loaded micelles had a mean size around 70 nm with narrow size distribution (polydispersity index, <0.1). The PTX‐loaded micelles showed sustained drug release and obvious anticancer activity similar to Taxol against HepG2 cells, whereas blank micelles were nontoxic. The present results suggest that the thermosensitive and biodegradable phe‐g‐PHPA‐g‐mPEG micelles are a promising delivery system for the hydrophobic drugs. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 3917–3924     

Paracetamol Sensor Based on Molecular Imprinting by Photosensitive Polymers

A voltammetric paracetamol sensor based on molecularly imprinted polymeric (MIP) micelles was prepared by direct electrodeposition. The MIP micelles were prepared via macromolecule self‐assembly of an amphiphilic photocrosslinkable copolymer using paracetamol as the template molecule. The resultant molecularly imprinted polymeric micelles swelled with increasing pH, and the disassociation of the micelles occurred at pH above approximately 7.4. A robust MIP film with good solvent resistance was formed on the electrode surface by anodic electrodeposition of the MIP micelles and subsequent photocrosslinking, resulting in the fabrication of a MIP electrochemical sensor for detecting paracetamol. The resultant sensor showed good response and selectivity towards paracetamol. In addition, a wide linear range from 0.01 mmol/L to 8 mmol/L and a low detection limit of 1×10^?6 mol/L for paracetamol detection was demonstrated based on this sensor. The MIP sensor also showed good stability and reversibility which was applied to determine paracetamol commercial tablets.     

pH敏感型mPEG-Hz-PLA聚合物纳米载药胶束的制备

以合成的含有腙键的聚乙二醇大分子(mPEG-Hz-OH)为引发剂,以丙交酯为单体引发开环聚合反应,并通过调整投料比,制备出3种不同分子量的含腙键的生物可降解嵌段聚合物(mPEG-Hz-PLA).将腙键引入到聚合物的骨架中,以此构建聚合物胶束并作为pH敏感型纳米药物载体.制备的pH敏感型胶束的CMC值等于或低于5.46×10-4 mg/m L,DLS和TEM显示粒径均小于100 nm,且粒径分布均匀.非pH敏感型胶束在不同pH下的粒径变化不明显,而pH敏感型胶束在酸性环境下(pH=4.0和pH=5.0)胶束粒径出现了明显变化.以阿霉素为模型药物制备了pH敏感型载药胶束,其粒径比空白胶束大(100~200 nm),且粒径分布均匀.药物释放实验表明pH敏感型载药胶束随着释放介质pH降低累积释药量增高.MTT实验表明空白胶束对HeLa细胞和RAW264.7细胞几乎没有抑制作用,而载阿霉素的胶束对2种细胞的抑制作用都随着剂量的增大和时间的延长而增强.     

Photocrosslinkable smart terpolymers responding to pH,temperature, and ionic strength

A series of copolymers of acrylic acid, N‐isopropylacrylamide (NIPAM), and cinnamoyloxyethyl acrylate were synthesized and studied. The polymers were responsive to four stimuli: UV light, temperature, pH, and ionic strength. The polymeric cinnamoyl chromophores underwent efficient photodimerization with concomitant photocrosslinking of the polymeric micelles. Because of the content of NIPAM, the terpolymers displayed a lower critical solution temperature, which could be controlled by the polymer composition, pH, and ionic strength. The ability to respond to the pH resulted from the content of acrylic carboxyl groups, which became protonated at low pHs. The changes in the polymer properties due to the application of the aforementioned stimuli were studied with pyrene and perylene as fluorescent probes. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3879–3886, 2004     

Thermosensitive and photocleavable polyaspartamide derivatives for drug delivery

The development of novel thermo‐ and photo‐dual‐responsive biodegradable polymeric micelles based on amphiphilic polyaspartamide derivatives (NB‐g‐PHPA‐g‐mPEG) for anticancer drug delivery is reported. The obtained polymers containing hydrophobic photocleavable o‐nitrobenzyl groups exhibit thermo‐ and photosensitivity. The micelles and paclitaxel‐loaded micelles based on the thermo‐ and photo‐dual‐sensitive polymers were prepared by a quick heating method without using toxic organic solvent. The paclitaxel release from the drug‐loaded micelles can be triggered under photoirradiation. Enhancement of the anticancer activity against HeLa cells was observed for paclitaxel‐loaded NB‐g‐PHPA‐g‐mPEG micelles after light irradiation, while the empty NB‐g‐PHPA‐g‐mPEG micelles with or without irradiation did not show any toxicity. Therefore, the thermo‐ and photo‐dual‐responsive NB‐g‐PHPA‐g‐mPEG micelles have a promising future applied as a light controlled drug delivery system for anticancer drugs. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2855–2863     

From well‐defined diblock copolymers prepared by a versatile atom transfer radical polymerization method to supramolecular assemblies

The synthesis of well‐defined diblock copolymers by atom transfer radical polymerization (ATRP) was explored in detail for the development of new colloidal carriers. The ATRP technique allowed the preparation of diblock copolymers of poly(ethylene glycol) (PEG) (number‐average molecular weight: 2000) and ionic or nonionizable hydrophobic segments. Using monofunctionalized PEG macroinitiator, ionizable and hydrophobic monomers were polymerized to obtain the diblock copolymers. This polymerization method provided good control over molecular weights and molecular weight distributions, with monomer conversions as high as 98%. Moreover, the copolymerization of hydrophobic and ionizable monomers using the PEG macroinitiator made it possible to modulate the physicochemical properties of the resulting polymers in solution. Depending on the length and nature of the hydrophobic segment, the nonionic copolymers could self‐assemble in water into nanoparticles or polymeric micelles. For example, the copolymers having a short hydrophobic block (5 < degree of polymerization < 9) formed polymeric micelles in aqueous solution, with an apparent critical association concentration between 2 and 20 mg/L. The interchain association of PEG‐based polymethacrylic acid derivatives was found to be pH‐dependent and occurred at low pH. The amphiphilic and nonionic copolymers could be suitable for the solubilization and delivery of water‐insoluble drugs, whereas the ionic diblock copolymers offer promising characteristics for the delivery of electrostatically charged compounds (e.g., DNA) through the formation of polyion complex micelles. Thus, ATRP represents a promising technique for the design of new multiblock copolymers in drug delivery. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3861–3874, 2001     

Bioinspired core‐crosslinked micelles from thymine‐functionalized amphiphilic block copolymers: Hydrogen bonding and photo‐crosslinking study

Bioinspired core‐bound polymeric micelles, based on hydrogen bonding and photo‐crosslinking, of thymine have been prepared from poly(vinylbenzylthymine)‐b‐poly(vinylbenzyltriethylammonium chloride). The amphiphilic block copolymer was synthesized by 2,2‐tetramethylpiperidin‐1‐oxyl‐mediated living radical polymerization in water/ethylene glycol solution. Micelle characterization and critical micelle concentration measurements demonstrated that the hydrogen bonding of the attached thymine units stabilizes the micelles. Further, core‐crosslinked polymeric micelles were formed by ultraviolet (UV) radiation showing that the stability of the micelle could be controlled by the UV crosslinking of the attached thymines. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Self‐assembly of amphiphilic tris(2,2′‐bipyridine)ruthenium‐cored star‐shaped polymers

Amphiphilic tris(2,2′‐bipyridine)ruthenium‐cored star‐shaped polymers consisting of one polystyrene block and two poly(N‐isopropylacrylamide) blocks were prepared by the “arm‐first” method in which RAFT polymerization and nonconvalent ligand–metal complexation were employed. The prepared amphiphilic star‐shaped metallopolymers are able to form micelles in water. The size and distribution of the micelles were studied by dynamic light scattering and transmission electron microscopy techniques. Preliminary studies indicate that the polymer concentration and the hydrophilic poly(N‐isopropylacrylamide) block length can affect the morphologies of the formed metal‐interfaced core–shell micelles in water. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4204–4210, 2007     

Molecular design of outermost surface functionalized thermoresponsive polymeric micelles with biodegradable cores

We prepared well‐defined diblock copolymers of thermoresponsive poly(N‐isopropylacrylamide‐co‐N,N‐dimethylacrylamide) blocks and biodegradable poly(D ,L ‐lactide) blocks by combination of reversible addition‐fragmentation chain transfer radical (RAFT) polymerization and ring‐opening polymerization. α‐Hydroxyl, ω‐dithiobenzoate thermoresponsive polymers were synthesized by RAFT polymerization using hydroxyl RAFT agents. Biodegradable blocks were prepared by ring‐opening polymerization of D ,L ‐lactide initiated by α‐hydroxyl groups of thermoresponsive polymers, which inhibit the thermal decomposition of ω‐dithioester groups. Terminal dithiobenzoate (DTBz) groups of thermoresponsive blocks were easily reduced to thiol groups and reacted with maleimide (Mal). In aqueous media, diblock copolymer products formed surface‐functionalized thermoresponsive micelles. These polymeric micelles had a low critical micelle concentration of 22 μg/L. In thermoresponsive studies of the micelles, hydrophobic DTBz‐surface micelles demonstrated a significant shift in lower critical solution temperature (LCST) to a lower temperature of 30.7 °C than that for Mal‐surface micelles (40.0 °C). In addition, micellar LCST was controlled by changing bulk mixture ratios of respective heterogeneous end‐functional diblock copolymers. Micellar disruption at acidic condition (pH 5.0) was completed within 5 days due to hydrolytic degradation of PLA cores, regardless of showing a slow disruption rate at physiological condition. Furthermore, we successfully improved water‐solubility of hydrophobic drug, paclitaxel by incorporating into the micellar cores. © Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7127–7137, 2008     

Synthesis of linear and star‐like poly(ε‐caprolactone)‐b‐poly{γ‐2‐[2‐(2‐methoxy‐ethoxy)ethoxy]ethoxy‐ε‐caprolactone} amphiphilic block copolymers using zinc undecylenate

Linear and star‐like amphiphilic diblock copolymers were synthesized by the ring‐opening polymerization of ε‐caprolactone and γ‐2‐[2‐(2‐methoxyethoxy)ethoxy]ethoxy‐ε‐caprolactone monomers using zinc undecylenate as a catalyst. These polymers have potential applications as micellar drug delivery vehicles, therefore the properties of the linear and 4‐arm star‐like structures were examined in terms of their molecular weight, viscosity, thermodynamic stability, size, morphology, and drug loading capacity. Both the star‐like and linear block copolymers showed good thermodynamic stability and degradability. However, the star‐like polymers were shown to have increased stability at lower concentrations with a critical micelle concentration (CMC) of 5.62 × 10^?4 g L^?1, which is less than half the concentration of linear polymer needed to form micelles. The star‐like polymeric micelles showed smaller sizes when compared with their linear counterparts and a higher drug loading capacity of doxorubicin, making them better suited for drug delivery purposes. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3601–3608     

Construction of nanostructures in aqueous solution from amphiphilic glucose‐derived polycarbonates

Carbohydrates are the fundamental building blocks of many natural polymers, their wide bioavailability, high chemical functionality, and stereochemical diversity make them attractive starting materials for the development of new synthetic polymers. In this work, one such carbohydrate, d ‐glucopyranoside, was utilized to produce a hydrophobic five‐membered cyclic carbonate monomer to afford sugar‐based amphiphilic copolymers and block copolymers via organocatalyzed ring‐opening polymerizations with 4‐methylbenzyl alcohol and methoxy poly(ethylene glycol) as initiator and macroinitiator, respectively. To modulate the amphiphilicities of these polymers acidic benzylidene cleavage reactions were performed to deprotect the sugar repeat units and present hydrophilic hydroxyl side chain groups. Assembly of the polymers under aqueous conditions revealed interesting morphological differences, based on the polymer molar mass and repeat unit composition. The initial polymers, prior to the removal of the benzylidenes, underwent a morphological change from micelles to vesicles as the sugar block length was increased, causing a decrease in the hydrophilic–hydrophobic ratio. Deprotection of the sugar block increased the hydrophilicity and gave micellar morphologies. This tunable polymeric platform holds promise for the production of advanced materials for implementation in a diverse range of applications. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 432–440     

Poly(ethylene glycol)-b-poly(epsilon-caprolactone) and PEG-phospholipid form stable mixed micelles in aqueous media

Novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEG(5000)-b-PCL(x)) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy poly(ethylene glycol) (PEG-DSPE), possess small size and high thermodynamic stability, raising their potential as long circulating carriers in the context of delivery of antineoplastic and antibiotic drugs. Formation of mixed polymeric micelles was confirmed using size exclusion chromatography and 1H NMR NOESY. Steady-state fluorescence measurements revealed depressed critical micellar concentrations indicative of a cooperative interaction between component hydrophobic blocks, which was quantified using the pseudophase model for micellization. Steady-state fluorescence measurements indicated that the mixed polymeric micelle cores possess intermediate micropolarity and high microviscosity. Pulsed field gradient spin-echo measurements were used to characterize micellar diffusion coefficients, which agree well with those obtained using dynamic light scattering. NOE spectra suggested that the hydrophobic polymer segments from individual components are in close proximity, giving evidence for the formation of a relatively homogeneous core. Contrary to one-component PEG(5000)-b-PCL(x) micelles, the mixed polymeric micelles could incorporate clinically relevant levels of the poorly water soluble antibiotic, amphotericin B (AmB). AmB encapsulation and release studies revealed an interesting composition-dependent interaction of the drug with the mixed polymeric micelle core.     

Self-assembled nanocages for hydrophilic guest molecules

Reverse polymeric micelles are obtained following the association of polymeric amphiphiles in apolar media. To this date, reports of pharmaceutical applications for such micelles have been scarce, mainly because these systems have been studied in solvents that are not suitable for medical use. Here, alkylated star-shaped poly(glycerol methacrylate) polymers have been proposed in the design of oil-soluble reverse polymeric micelles. Micellar behavior was studied in various apolar solvents, including ethyl oleate, a pharmaceutically acceptable vehicle. The polymers were shown to assemble into spherical nanostructures (<40 nm) as determined by cryogenic transmission electron microscopy and atomic force microscopy studies. Interestingly, the reverse micelles were able to encapsulate various peptides/proteins (vasopressin, myoglobin, and albumin) in substantial amounts and facilitate their solubilization in oil. The nature of both the polymer used in micelle formation and the guest molecules was found to influence the ability of the micelle to interact with hydrophilic compounds.     

Synthesis and characterization of biodegradable pH and reduction dual‐sensitive polymeric micelles for doxorubicin delivery

Novel pH and reduction dual‐sensitive biodegradable polymeric micelles for efficient intracellular delivery of anticancer drugs were prepared based on a block copolymer of methyloxy‐poly(ethylene glycol)‐b‐poly[(benzyl‐l ‐aspartate)‐co‐(N‐(3‐aminopropyl) imidazole‐l ‐aspartamide)] [mPEG‐SS‐P(BLA‐co‐APILA), MPBA] synthesized by a combination of ring‐opening polymerization and side‐chain reaction. The pH/reduction‐responsive behavior of MPBA was observed by both dynamic light scattering and UV–vis experiments. The polymeric micelles and DOX‐loaded micelles could be prepared simply by adjusting the pH of the polymer solution without the use of any organic solvents. The drug release study indicated that the DOX‐loaded micelles showed retarded drug release in phosphate‐buffered saline at pH 7.4 and a rapid release after exposure to weakly acidic or reductive environment. The empty micelles were nontoxic and the DOX‐loaded micelles displayed obvious anticancer activity similar to free DOX against HeLa cells. Confocal microscopy observation demonstrated that the DOX‐loaded MPBA micelles can be quickly internalized into the cells, and effectively deliver the drugs into nuclei. Thus, the pH and reduction dual‐responsive MPBA polymeric micelles are an attractive platform to achieve the fast intracellular release of anticancer drugs. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 1771–1780     

Investigation of pH-responsive properties of polymeric micelles with a core-forming block having pendant cyclic ketal groups

In this study, three kinds of amphiphilic block copolymers, termed MPEG-block-PDMMA, MPEG-block-PCPMA, and MPEG-block-PMPMA, which were composed of one hydrophilic monomethoxy poly(ethylene glycol) (MPEG) block and one hydrophobic polyacrylate block bearing pendant six-member cyclic ketal groups, were synthesized by atom transfer radical polymerization (ATRP). These polymers can disperse in aqueous media to self-assemble into micellar aggregates with a spherical core-shell structure with mean diameter below 300 nm. The stimuli-responsiveness of polymeric micelles from MPEG-block-PDMMA was detected by fluorescence-probe technique at pH 3.5 and 37 °C. The effect of chemical architecture and composition of the polymers on the pH-responsive properties of polymeric micelles was also studied. A combination of pH and temperature to trigger release behavior of these polymeric micelles was discussed by comparing the encapsulated molecule release ability under various pH and temperature conditions and analyzing chemical structural changes of the polymer before and after the triggering.     

Structure of water incorporated in sulfobetaine polymer films as studied by ATR-FTIR

The structure and hydrogen bonding of water in the vicinity of a thin film of a sulfobetaine copolymer (poly[(N,N-dimethyl-N-(3-sulfopropyl)-3'-methacrylamidopropanaminium inner salt)-ran-(butyl methacrylate)], poly(SPB-r-BMA)), were analyzed with band shapes of O-H stretching of attenuated total reflection infrared (ATR-IR) spectra. The copolymer could be cast as a thin film, of approximate thickness 10 microm, on a ZnSe crystal for the ATR-IR spectroscopy. At an early stage of sorption of water into the polymer film, the O-H stretching band of the IR spectra for the water incorporated in the film was similar to that for free water. This is consistent with the tendency for another zwitterionic polymeric material, poly[(2-methacryloyloxyethylphosphorylcholine)-ran-(butyl methacrylate)] (poly(MPC-r-BMA). It is, however, contradictory to the drastic change in the O-H stretching band for water incorporated into films of polymers such as poly(2-hydroxyethyl methacrylate), poly(methyl methacrylate) and poly(butyl methacrylate). These results suggest that polymers with a zwitterionic structure do not significantly disturb the hydrogen bonding between water molecules incorporated in the thin films. The investigation into the blood-compatibility of both the poly(SPB-r-BMA) and the poly(MPC-r-BMA) films indicate a definite correlation between the blood-compatibility of the polymers and the lack of effect of the polymeric materials on the structure of the incorporated water.     

Amphiphilic Block Copolymer Micelles for Gene Delivery

Gene therapy is a promising method to treat acquired and inherited diseases by introducing exogenous genes into specific recipient cells. Polymeric micelles with different nanoscopic morphologies and properties hold great promise for gene delivery system. Conventional cationic polymers, poly(ethyleneimine)(PEI), poly(L-lysine)(PLL), poly(2-dimethyla-minoethyl methacrylate)(PDMAEMA) and novel cationic polymers poly(2-oxazoline)s(POxs), have been incorporated into block copolymers and decorated with targeting moieties to enhance transfection efficiency. In order to minimize cytotoxicity, nonionic block copolymer micelles are utilized to load gene through hydrophilic and hydrophobic interactions or covalent conjugations, recently. From our perspective, properties(shape, size, and mechanical stiffness, etc.) of block copolymer micelles may significantly affect cytotoxicity, transfection efficiency, circulation time, and load capacity of gene vectors in vivo and in vitro. This review briefly sums up recent efforts in cationic and nonionic amphiphilic polymeric micelles for gene delivery.     

Synthesis and characterization of core–shell‐type polymeric micelles from diblock copolymers via reversible addition–fragmentation chain transfer

A method was developed to enable the formation of nanoparticles by reversible addition–fragmentation chain transfer polymerization. The thermoresponsive behavior of polymeric micelles was modified by means of micellar inner cores and an outer shell. Polymeric micelles comprising AB block copolymers of poly(N‐isopropylacrylamide) (PIPAAm) and poly(2‐hydroxyethylacrylate) (PHEA) or polystyrene (PSt) were prepared. PIPAAm‐b‐PHEA and PIPAAm‐b‐PSt block copolymers formed a core–shell micellar structure after the dialysis of the block copolymer solutions in organic solvents against water at 20 °C. Upon heating above the lower critical solution temperature (LCST), PIPAAm‐b‐PHEA micelles exhibited an abrupt increase in polarity and an abrupt decrease in rigidity sensed by pyrene. In contrast, PIPAAm‐b‐PSt micelles maintained constant values with lower polarity and higher rigidity than those of PIPAAm‐b‐PHEA micelles over the temperature range of 20–40 °C. Structural deformations produced by the change in the outer polymer shell with temperature cycles through the LCST were proposed for the PHEA core, which possessed a lower glass‐transition temperature (ca. 20 °C) than the LCST of the PIPAAm outer shell (ca. 32.5 °C), whereas the PSt core with a much higher glass‐transition temperature (ca. 100 °C) retained its structure. The nature of the hydrophobic segments composing the micelle inner core offered an important control point for thermoresponsive drug release and the drug activity of the thermoresponsive polymeric micelles. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 3312–3320, 2006     

Divergent synthesis and self‐assembly of amphiphilic polymeric dendrons with selective degradable linkages

Enhancing the structural complexity and functionality of the building blocks allows the construction of supramolecular assemblies. In this work, we demonstrate a strategy for the design and synthesis of complex macromolecular architectures. We use atom transfer radical polymerization to produce well‐defined polymers with telechelic end‐group functionality, and “click” them together to form functional 3rd generation dendrons, and incorporated degradable linkages and certain functionality at the polymer chain‐ends of each generation. The 3rd generation polymeric dendrons consisted of homopolymer polystyrene (PSTY) with either four solketals or eight alcohols, diblock PSTY and poly(t‐butyl acrylate), and amphiphilic diblock. The peripheral ends consisting of alcohols create functionalization points for further chemical modification or chemical coupling and the cleavable linkages between the 2nd and 3rd generations all provide the first steps toward smart nanostructures. Importantly, we can synthesize these dendrons in pure form. The self‐assembly of the amphiphilic dendrons (the inner and outer generations consisting of PSTY and polyacrylic acid, respectively) in water produced micelles of uniform size with an aggregation number of 43 dendrons per micelle. The size of the micelles was small (D_H =20.7 nm) and comparable to the size found by transmission electron microscopy (14–18 nm). © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1533–1547, 2008     

Conjugation of arginine–glycine–aspartic acid peptides to thermoreversible N‐isopropylacrylamide polymers

Thermoreversible polymeric biomaterials are finding increased acceptance in tissue engineering applications. One drawback of the polymers is their synthetic nature, which does not allow direct interaction of mammalian cells with the polymers. This limitation may be alleviated by grafting arginine–glycine–aspartic acid (RGD) containing peptides onto the polymer backbone to facilitate interactions with cell‐surface integrins. Toward this goal, N‐isopropylacrylamide (NiPAM)‐based thermoreversible polymers containing amine‐reactive N‐acryloxysuccinimide (NASI) groups were synthesized. Conjugation of RGD‐containing peptides to polymers was demonstrated with ¹H NMR spectroscopy and reverse‐phase high‐pressure liquid chromatography. The conjugation reaction was optimal at 4 °C and pH of 8.0, and increased with the increasing NASI content of polymers. With a peptide grafting ratio of 0.25 mol %, there was no significant change in the lower critical solution temperature of the polymers. Finally, the NASI‐containing polymers, cast as films, on tissue culture polystyrene, were shown to conjugate to RGD‐containing peptides and support C2C12 cell attachment. We conclude that NASI‐containing thermoreversible polymers are amenable for grafting biomimetic peptides to impart cell adhesiveness to the polymers. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3989–4000, 2003