N‐(2‐hydroxypropyl)methacrylamide‐based polymer conjugates with pH‐controlled activation of doxorubicin. I. New synthesis,physicochemical characterization and preliminary biological evaluation

New method of synthesis of water‐soluble polymer‐drug conjugates, exhibiting remarkable anticancer activity in mice models, has been developed. In the conjugates, an anticancer drug doxorubicin (DOX) is attached to a polymer carrier based on N‐(2‐hydroxypropyl)methacrylamide (HPMA) copolymer via a hydrolytically labile hydrazone bond. New methacrylamide‐type comonomers, containing either hydrazide group or hydrazon of DOX, were used for copolymerization with HPMA. In contrast to the synthetic procedure described earlier the new method is simpler, cheaper, and results in a better‐defined conjugate structure. The conjugates are fairly stable in buffer at pH 7.4 (model of blood stream) but release DOX under mild acid conditions modeling the tumor microenvironment. The conjugates showed significant in vivo antitumor activity in treatment of T‐cell lymphoma EL‐4 bearing mice with up to 100% long‐term survivors. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

A polymer–drug conjugate for doxorubicin: Synthesis and biological evaluation of pluronic F127‐doxorubicin amide conjugates

Higher molecular weight of the polymer carrier is the basis for enhanced accumulation of the pro‐drug in a solid tumor tissue due to a tumor‐related phenomenon described as the enhanced permeability and retention (EPR) effect. The anticancer drug doxorubicin was covalently bound to F127 through amide group susceptible to lysosomal hydrolysis. The in vitro and in vivo properties of F127‐DOX amide conjugates were studied. F127‐DOX amide conjugates (M_w: 13,400) were stable in neutral circumstance and showed the potency and mechanism of action of the released drug. In the in vivo experiment, results showed that F127‐DOX amide conjugates prolonged blood circulation and lowered in vivo toxicity than corresponding DOX, which illustrated the importance of molecular weight. The results demonstrated that F127‐DOX amide conjugates may be very promising and clinically suitable candidates for anticancer therapy. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Comparative mucoadhesive study of hyaluronic acid‐based conjugates on different mucosae

The incentive of this study was to provide a detailed mucoadhesive comparison on adhesive properties on diverse mucosal surfaces such as nasal, buccal, and vaginal mucosa, respectively. Mucoadhesive hyaluronic acid–cysteine ethyl ester (HA–SH) conjugate was synthesized by the anchorage of sulfhydryl groups (SH) on the polymeric backbone of HA via amide bond formation between the carboxylic acid moieties of hyaluronic acid and sulfhydryl groups of cysteine ethyl ester. Histology assay in terms of alcian blue staining was performed on mucosal tissue in order to evaluate the potential impact on viability. The proficiency of water uptake was studied in various simulated body fluid. Moreover, mucoadhesive assays based on rotating cylinder, total work of adhesion, and maximum detachment force were carried out on various mucosae. The findings revealed in presence of 2.7‐, 2.6‐, and 1.25‐fold improvement in swelling behavior in comparison to unmodified HA on nasal, buccal, and vaginal mucosa. Furthermore, mucoadhesive studies showed a 3.2‐, 2.6‐, 2.6‐fold more extended residence time on nasal, buccal, and vaginal in presence of HA–SH in comparison to unmodified HA, respectively. Taken together, the comprehensive mucoadhesive study serve as guidance in the development of mucoadhesive drug delivery systems for versatile application. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46071.     

Preparation and aqueous solution behavior of a ph‐responsive branched copolymer based on 2‐(diethylamino)ethyl methacrylate

pH‐Responsive amphiphilic branched copolymers were prepared from poly(ethylene glycol) methyl ether methacrylate (PEGMA), 2‐(diethylamino)ethyl methacrylate (DEAEMA), 2‐(tert‐butylamino)ethyl methacrylate (tBAEMA), and ethylene glycol dimethacrylate (EGDMA) utilizing a thiol‐modified free radical polymerization. The molecular structures of copolymers were confirmed by proton nuclear magnetic resonance spectroscopy (¹H NMR) and triple‐detection gel permeation chromatography (tri‐GPC). The aqueous solution behaviors of the obtained copolymers were investigated by dynamic light scattering (DLS). The DLS data showed that about 16 nm polymer particles comprising of hydrophobic poly(tert‐butylamino)ethyl methacrylate (PtBAEMA) and poly(diethylaminoethyl methacrylate (PDEAEMA) core, hydrophilic PEGMA corona were formed above pH 8. With the decrease of pH from 8 to 6, a dramatic increase in the hydrodynamic radius of polymer particles from 16 nm to 130 nm was observed resulting from the protonation of the PDEAEMA segment. Moreover, in vitro drug release behaviors of the resulting polymer assemblies at different pH values were also investigated to evaluate their potential as sustained release drug carriers. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42183.     

Preparation of glucose‐sensitive and fluorescence micelles via a combination of photoinitiated polymerization and chemoenzymatic transesterification for the controlled release of insulin

Glucose‐sensitive and fluorescence copolymer micelles were designed and prepared via a combination of photoinitiated polymerization and enzymatic transesterification. The water‐soluble photoinitiator and emulsifier 2‐oxooctanoic acid self‐polymerized dimer molecules under UV irradiation were characterized by mass spectrometry. The fluorescence dye (9‐anthracene alcohol) and biocompatible hydrophilic chains [poly(ethylene glycol)] were introduced to the polymer chains during the photopolymerization and enzymatic transesterification processes. The as‐prepared copolymers were confirmed by ¹H‐NMR spectroscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, and dynamic light scattering. The resulting copolymers exhibited excellent glucose sensitivity and stability against protein. The optical fluorescence properties of the copolymer micelles were investigated with fluorescence spectrophotometry, fluorescence microscopy, and confocal laser scanning microscopy. Because of the amphiphilic feature, the micelles could be self‐assembled and used to load insulin. The controlled release of insulin was evaluated and was triggered by glucose in vitro. This study provided a new strategy for fabricating functional carriers as self‐regulated insulin‐release systems. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43026.     

Synthesis and characterization of a drug‐delivery system based on melamine‐modified poly(vinyl acetate‐co‐maleic anhydride) hydrogel

Three‐dimensional polymeric networks, which quickly swell by imbibing a large amount of water or deswell in response to changes in their external environment, are called hydrogels. These types of polymeric materials are good potential candidates for drug‐delivery systems. In this study, we first synthesized poly(vinyl acetate‐co‐maleic anhydride) by free‐radical copolymerization. Then, they were modified with different molar ratios of melamine to prepare hydrogels that could be used in drug‐delivery systems. The hydrogels were characterized by Fourier transform infrared spectroscopy, ¹H‐NMR, differential scanning calorimetry, and scanning electron microscopy. In the second step, Ceftazidime antibiotic was loaded on selected hydrogels. The in vitro drug release was investigated and compared in three different media (HCl solution at pH = 3 and buffer solutions at pH 6.1and pH 8). © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40389.     

Fabrication of size‐controllable mPEG‐decorated microparticles conjugating optically active ketoprofen based on self‐assembly of amphiphilic random copolymers

Novel size‐controllable mPEG‐decorated polymeric microparticles binding optically active ketoprofen were successfully fabricated based on chemoenzymatic synthesis and self‐assembly of amphiphilic random polymer–ketoprofen conjugates with mPEG and (S)‐ketoprofen as pendants. A series of mPEG₃₅₀‐ or mPEG₁₀₀₀‐functionalized amphiphilic random polymer–ketoprofen conjugates with drug loading capacity from 16.5% to 73.2% were easily prepared by combining enzymatic resolution with radical polymerization and characterized by Fourier Transform Infrared spectroscopy, ¹H‐NMR, and gel permeation chromatography. The formation of aggregates from the amphiphilic random polymer–ketoprofen conjugates was investigated by ultraviolet‐visible absorption spectra using pyrene as the guest molecule. Transmission electron microscopy measurement revealed that the self‐assemblies were well dispersed as spherical microparticles. The size of the self‐assemblies could be widely tuned by varying the length of mPEG chains and the content of ketoprofen in the synthetic polymer–ketoprofen conjugates, and a series of mPEG‐decorated (S)‐ketoprofen‐bound polymeric microparticles with average radius from 70 nm to 1.1 μm were obtained. The successful preparation of the microparticles containing (S)‐ketoprofen provided a new strategy for the design and fabrication of optically active drug delivery systems. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Synthesis and In vitro cytotoxicity of poly(ethylene glycol)–epothilone B conjugates

Natural epothilone B (EPOB) is currently in clinical trials for treatment of advanced cancers. In this study, two poly(ethylene glycol) (PEG)–EPOB conjugates were synthesized with carbodiimide chemistry with linear PEG Methoxy‐PEG‐Carboxymethy(mPEG‐COOH) with different molecular weights (5 and 20 kDa). The products were confirmed by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectroscopy and ¹H‐NMR, which showed that PEGylation only took place at the 7‐OH site of EPOB. The solubilities of PEG5K–EPOB the conjugate of mPEG‐COOH (MW 5,000) and epothilone B and PEG20K–EPOB the conjugate of mPEG‐COOH (MW 20,000) and epothilone B were determined to be 4.93 × 10^?2 and 1.58 × 10^?2 mmol/mL; this showed improvements of 35 and 11 times, respectively, over that of free EPOB (1.4 × 10^?3 mmol/mL). Moreover, the conjugates were more stable than that of free EPOB in plasma. The cytotoxicity of conjugates was evaluated on human breast cancer MCF‐7 cells with an 3‐(4,5)‐dimethylthiahiazo (‐z‐y1)‐3,5‐di‐ phenytetrazoliumromide(MTT) based assay. The half maximal inhibitory concentration of a substance(IC50) values of EPOB, PEG5K–EPOB, and PEG20K–EPOB were 6.0 × 10^?4, 0.57, and 8.4 × 10^?3 μM, respectively. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41123.     

Controlled delivery of growth‐hormone‐releasing peptide 6 from the poly(lactic‐co‐glycolic acid)–poly(ethylene glycol)–poly(lactic‐co‐glycolic acid) copolymer and the effect of a growth‐hormone‐releasing peptide 6–copolymer hydrogel on the growth of rex rabbits

Growth‐hormone‐releasing peptide 6 (GHRP‐6) plays an important role in animal growth. However, there have been few studies focusing on the effect of GHRP‐6 on animal growth through controlled release systems. We synthesized the poly(lactic‐co‐glycolic acid) (PLGA)–poly(ethylene glycol) (PEG)–PLGA copolymer to investigate its controlled released effect on GHRP‐6 in vitro and to study the effect of a GHRP‐6–copolymer hydrogel on the growth of rex rabbits. The copolymer was synthesized with ring‐opening copolymerization and characterized by ¹H‐NMR. The interaction between GHRP‐6 and the copolymer was characterized by Fourier transform infrared spectroscopy and X‐ray diffraction. The body weight, serum level of insulin‐like growth factor 1 (IGF‐1), and hair coat quality were studied in rex rabbits. The results show that hydrogen bonds formed between the N? H group in GHRP‐6 and the C?O group in the copolymer. The release mechanism of GHRP‐6 was a combination of a diffusion‐controlled mechanism and an erosion‐controlled mechanism in the copolymer. The serum level of IGF‐1, hair coat quality, and body weight were all significantly higher in the GHRP‐6–copolymer hydrogel group than in the other groups. These results indicate that the copolymer effectively controlled the release of GHRP‐6. In addition, the GHRP‐6–copolymer hydrogel increased the synthesis of IGF‐1 for a prolonged period and, thereby, increased the rex rabbits' growth and hair coat quality. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40185.     

pH‐sensitive hydroxyethyl starch–doxorubicin conjugates as antitumor prodrugs with enhanced anticancer efficacy

Doxorubicin (DOX) is a widely used chemotherapeutic drug for the treatment of several types of cancers, which has limitation in clinical applications because of severe heart toxicity. Herein, to reduce the fast clearance from the blood system and the severe systemic toxicity caused by the nonspecific protein adsorption, a pH‐sensitive drug delivery system with higher drug conjugated content was prepared by conjugating DOX onto hydroxyethyl starch (HES) with a pH‐sensitive hydrazone bond. In normal physiological environment, the release of DOX conjugated onto HES was slight which could be neglected without any side effect. However, in an acidic environment mimicking the tumor microenvironment, this pH‐sensitive hydrazone linkage provided a controlled and sustained release of DOX over a period of more than 3 days. The conjugates had good biocompatibility, long circulation, and lower cytotoxicity, which could efficiently be transferred into HeLa and HepG2 cells and release the conjugated drug. Based on these promising properties, these HES–DOX conjugates outline the significant potential for future biomedical application in the controlled release of antitumor drugs. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42778.     

Self‐aggregates of cholic acid hydrazide–dextran conjugates as drug carriers

Cholic acid hydrazide–dextran conjugates (CAH–DEX's) with stable acryl hydrazone linkages were synthesized from cholic acid hydrazide and poly(aldehyde dextran) and were characterized by Fourier transform infrared (FTIR) spectroscopy, ¹H‐NMR, and surface tension measurements. The conjugates developed a lower critical aggregation concentration, which was determined by 1,6‐diphenyl‐1,3,5‐hexatriene dye solubilization methods, 1.41 and 2.10 × 10^?2 mg/mL for CAH–DEX 9.0 and CAH–DEX 6.5, respectively. A hydrophobic drug, indomethacin (IN), was physically entrapped inside the self‐aggregates, and the IN‐loaded self‐aggregates were analyzed with a dynamic light‐scattering system, transmission electron microscopy, and atomic force microscopy. The maximum loading of IN reached 29.9% of the CAH–DEX self‐aggregates, which suggested a high loading efficiency of 51.2%. The size of the self‐aggregates increased when the drug was entrapped. IN was released from CAH–DEX self‐aggregates at pH 4 much slower than at pH 7.4, and in pH 4 media, the release profile was pseudo‐zero‐order in kinetic terms for up to 14 days. There was almost no change in the FTIR spectra of the CAH–DEX's, which were incubated in buffers of pH 7.4 and pH 4 for 24 h, which indicated that acryl hydrazone was considerably resistant to hydrolysis. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 95: 487–493, 2005     

Synthesis,characterization, and cytotoxicity of star‐shaped polyester‐based elastomers as controlled release systems for proteins

With the growing number of therapeutic proteins on the market, effective delivery systems are receiving particular attention. In this study, biodegradable elastomers, intended for protein drug delivery and based on methacrylic tripoly(ε‐caprolactone‐co‐d ,l ‐lactide) cyclic ester with different ratios of ?‐caprolactone to d ,l ‐lactide and methacrylic bipoly[?‐caprolactone‐b‐poly(ethylene glycol)‐b‐?‐caprolactone], were synthesized and characterized. The degradation behavior, bovine serum albumin (BSA)‐releasing kinetics, and cytotoxicity of the elastomers in vitro were investigated. The elastomers were degraded by the hydrolysis of the ester bond; this resulted in pH changes, which further affected the degradation rate. The BSA‐releasing behavior was strongly dependent on the diffusion mechanism. In the diffusion‐controlled period, nearly sustained and stable BSA release was achieved. Furthermore, the elastomers displayed good biocompatibility, as demonstrated by a 3‐(4,5‐dimethyl thiazol‐2‐yl)?2,5‐diphenyl tetrazolium bromide assay and inflammation–induction experiments, and are considered promising candidates for the controllable delivery of protein drugs. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43393.     

Development and characterization of gelatin–polysaccharide based phase‐separated hydrogels for prevention of sexually transmitted diseases

Bacterial vaginosis is a sexually transmitted vaginal infection prevalent in sexually active women. Gelatin–polysaccharide phase‐separated hydrogels were prepared and characterized as vaginal delivery systems for the treatment of bacterial vaginosis. Sodium carboxymethyl cellulose, maltodextrin, and dextran were used as the representative polysaccharides. The developed gels were characterized by impedance spectrometer, X‐ray diffraction (XRD) studies, and differential scanning calorimetry. The mucoadhesivity, water absorption, and hemocompatibility of the gels were also studied. The gels were electrically conductive in nature and showed a concentration‐dependent behavior. XRD study suggested the amorphous nature of the hydrogels. An increase in the polysaccharide content increased the water holding capacity of the gels. The gels were found to possess mucoadhesive property and were hemocompatible. Metronidazole, a commonly used drug for treating bacterial vaginosis, loaded gels showed diffusion‐mediated drug release. The drug‐loaded hydrogels showed good antimicrobial activity. In gist, the developed hydrogels may be tried as matrices for vaginal delivery of antimicrobials. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41785.     

Synthesis and characterization of novel biodegradable polymeric prodrugs containing 5‐fluorouracil and 4‐amino‐N‐(2‐pyrimidinyl) benzene sulfonamide terminal groups

To develop novel biodegradable polymeric prodrugs with target‐directing and drug‐active functional groups, a series of polymeric antitumor prodrugs containing sulfadiazine and 5‐fluorouracil terminal groups were prepared via the two‐step reaction of chlorinated poly(lactic acid) or chlorinated poly(lactic acid‐co‐glycolic acid) with potassium sulfadiazine (SF‐K) and 1,3‐dihydroxymethyl‐5‐fluorouracil. The synthesized polymers were characterized by means of infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, gel permeation chromatography, viscosity measurements, differential scanning calorimetry, and ultraviolet (UV) spectroscopy. The GA/LA value was varied, so that the effects of the comonomer content on the solubility, thermal properties, and degradable behaviors were examined respectively. It was found that introducing the GA units could increase the melting temperature (T_m), the hydrolytic degradation, and the hydrophilicity, while it decreased the glass transition temperature (T_g). The drug content of 5‐FU measured by UV spectra is 56.3 in maximum. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Thiol–norbornene photoclick hydrogels for tissue engineering applications

Thiol–norbornene (thiol–ene) photoclick hydrogels have emerged as a diverse material system for tissue engineering applications. These hydrogels are crosslinked through light‐mediated orthogonal reactions between multifunctional norbornene‐modified macromers [e.g., poly(ethylene glycol) (PEG), hyaluronic acid, gelatin] and sulfhydryl‐containing linkers (e.g., dithiothreitol, PEG–dithiol, biscysteine peptides) with a low concentration of photoinitiator. The gelation of thiol–norbornene hydrogels can be initiated by long‐wave UV light or visible light without an additional coinitiator or comonomer. The crosslinking and degradation behaviors of thiol–norbornene hydrogels are controlled through material selections, whereas the biophysical and biochemical properties of the gels are easily and independently tuned because of the orthogonal reactivity between norbornene and the thiol moieties. Uniquely, the crosslinking of step‐growth thiol–norbornene hydrogels is not oxygen‐inhibited; therefore, gelation is much faster and highly cytocompatible compared with chain‐growth polymerized hydrogels with similar gelation conditions. These hydrogels have been prepared as tunable substrates for two‐dimensional cell cultures as microgels and bulk gels for affinity‐based or protease‐sensitive drug delivery, and as scaffolds for three‐dimensional cell encapsulation. Reports from different laboratories have demonstrated the broad utility of thiol–norbornene hydrogels in tissue engineering and regenerative medicine applications, including valvular and vascular tissue engineering, liver and pancreas‐related tissue engineering, neural regeneration, musculoskeletal (bone and cartilage) tissue regeneration, stem cell culture and differentiation, and cancer cell biology. This article provides an up‐to‐date overview on thiol–norbornene hydrogel crosslinking and degradation mechanisms, tunable material properties, and the use of thiol–norbornene hydrogels in drug‐delivery and tissue engineering applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41563.     

Synthesis,characterization, and in vitro drug release study of 3‐arm poly‐β‐alanine

Synthesis of three arms star‐shaped poly‐β‐alanine (3‐b‐ala) based on tri(prop‐2‐yn‐1‐yl) benzene‐1,3,5‐tricarboxylate (TBT) and azido terminated poly‐β‐alanine (N₃‐P‐ala) was performed using click reaction. TBT was synthesized by nucleophilic substitution reaction between propargyl alcohol and 1,3,5‐benzenetricarbonyltrichloride. For the first time, N₃‐P‐ala was synthesized through anionic polymerization of acrylamide using sodium azide as an initiator. TBT was characterized by FT‐IR and ¹HNMR. N₃‐p‐ala was characterized by FT‐IR, GPC, and ¹HNMR and 3‐b‐ala was characterized by FT‐IR, GPC, ¹HNMR, TGA, and XRD. The synthesized 3‐b‐ala was used for drug loading and releasing studies. Polymer loaded drug (3‐b‐ala‐D) hybrid was used in in vitro studies of drug (Diclofenac sodium) release in phosphate buffer solution (PBS) at 37 ± 0.5°C and pH 7.4. The drug loading and releasing studies were analyzed by UV‐visible spectrophotometer. 3‐b‐ala‐D was examined by AFM to analyze the surface morphology and roughness. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42124.     

The architecture of hydroxy‐functionalized aPS‐b‐random copolymer‐b‐PE via one‐pot strategy combining living free radical polymerization with coordination polymerization

The copolymerization of styrene with ethylene was promoted by CpTiCl₃/BDGE/Zn/MAO catalyst system combining free radical polymerization with coordination polymerization via sequential monomer addition strategy in one‐pot. The effect of polymerization conditions such as temperature, time, ethylene pressure, and Al/Ti molar ratio on the polymerization performance was investigated. The hydroxy‐functionalized aPS‐b‐random copolymer‐b‐PE triblock copolymer was obtained by solvent extraction and determined by GPC, DSC, WAXD, and ¹³C‐NMR. The DSC result indicated that the aPS‐b‐random copolymer‐b‐PE had a T_g at 87°C and a T_m at 119°C which attributed to the T_g of aPS segment and the T_m of PE segment, respectively. The microstructure of the hydroxy‐functionalized aPS‐b‐random copolymer‐b‐PE was further confirmed by WAXD, ¹³C‐NMR, and ¹H‐NMR analysis; and these results demonstrated that the obtained block copolymer consisted of aPS segment, S‐E random copolymer segment, and crystalline PE segment. The connection polymerization of the hydroxy‐functionalized aPS with random copolymer‐b‐PE was revealed by GPC results. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

New amoxicillin–poly(lactic acid)‐based conjugates: synthesis and in vitro release of amoxicillin

Long‐term antibiotic treatments are required to cure many diseases. Coupling a bioactive compound to a biocompatible polymer offers, in general, many advantages such as better stabilization of drug and controlled release. The work reported deals with the synthesis of new conjugates based on amoxicillin and oligomers of biocompatible and biodegradable poly(lactic acid), as well as release studies of amoxicillin. These new conjugates were obtained via a Curtius rearrangement or acyl chloride activation, leading to substituted urea or amide bonds between amoxicillin and polymer, respectively. Structures of the conjugates were assessed using Fourier transform infrared and ¹H NMR spectroscopy, double‐detection size exclusion chromatography and electrospray ionization mass spectrometry. In vitro release profiles of amoxicillin in phosphate buffered saline were determined using high‐performance liquid chromatography, and the release rates of amoxicillin from the two conjugates were compared. Copyright © 2010 Society of Chemical Industry     

“One‐pot” synthesis of well‐defined functional copolymer and its application as tumor‐targeting nanocarrier in drug delivery

A one‐pot synthesis is developed for PEG₆₀₀‐b‐poly(glycerol monoacrylate) (PEG₆₀₀‐b‐PGA), by which folate and superparamagnetic iron oxide nanoparticles (SPIONs) are assembled to form folic acid‐conjugated magnetic nanoparticles (FA‐MNPs) as a tumor targeting system. The synthesis consists of a “click” reaction and atom transfer radical polymerization (ATRP) to obtain the well‐defined furan‐protected maleimido‐terminated PEG₆₀₀‐b‐poly(solketal acrylate) (PEG₆₀₀‐b‐PSA) copolymer. After deprotection, the key copolymer N‐maleimido‐terminated PEG₆₀₀‐b‐PGA is successfully conjugated with thiol derivatives of folate and FITC, respectively. FA‐MNPs are developed by assembling of the resulting polymer FA‐PEG₆₀₀‐b‐PGA with SPIONs, and characterized for their size, surface charge, and superparamagnetic properties. To investigate the cellular uptake of the nanoparticles by Hela cells and φ2 cells using fluoresce technique, FA‐FITC‐MNPs are also obtained by assembling of FA‐PEG₆₀₀‐b‐PGA, FITC‐PEG₆₀₀‐b‐PGA with SPIONs. Qualitative and quantitative determinations of FA‐FITC‐MNPs show that the particles specifically internalized to Hela cells. No significant cytotoxicity is observed for these two kinds of cell lines. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40405.