Self-assembled monolayer of carboxyl-terminated poly(amido amine) dendrimer

Adlayer formation and adsorption structure of 2.5th-generation poly(amido amine) dendrimer with carboxyl-terminated groups on solid substrates were investigated by atomic force microscopy, surface plasmon resonance spectroscopy, and surface enhanced infrared absorption spectroscopy. Dendrimer molecules are not uniformly adsorbed on solid surface but form aggregates with a width of approximately 100 nm and a height less than 1 nm. Adsorption reaches in equilibrium at 100-1000 sec, depending on the dendrimer concentration. The adsorption-desorption process is considerably reproducible and repeatable. Although the adsorption at equilibrium increases with dendrimer concentration and reaches maximum at neutral pH, monolayer is always maintained after the desorption with solvent. This indicates the formation of self-assembled monolayer. Such monolayer is preserved even at the variation of pH. Although most carboxylates are protonated at acidic pH, small amount of carboxylate remains even at acidic pH. The adsorption structure of dendrimer was illustrated.     

Direct formation of platinum nanoparticles by internally isopropanol-modified dendritic poly(amido amine)

We report a reducing agent-free method for preparing platinum (Pt) nanoparticles by internally isopropanol (IPA)-modified dendritic poly(amido amine) (PAMAM). The internally modified dendritic PAMAM were synthesized via divergent strategy using 1,3-diaminopropanol as a linking spacer, and NMR analyses confirm the embedded IPA moieties within the dendrimers by the appearance of characteristic proton and carbon resonances at 3.81 and 67.9 ppm, respectively. The in situ formation of stable Pt colloids was carried out by thermal treatment in the presence of internally modified dendritic PAMAM bearing either ester or alcohol peripherals, suggesting that the internal IPA functionalities dominate the reduction of Pt4+ ions. Moreover, the overall reducing rate was accelerated with increasing pH values. This result agreed with a reaction feature for preparing metal nanocomposites through polyol process in which basic environment facilitates the thermal-promoted reduction of metal ions accompanied with the oxidation of internal hydroxyl groups. The morphology of the dendrimer/Pt composite monitored by a transmission electron microscope (TEM) exhibited narrowly dispersed and roughly spherical shaped nanoparticles with a mean diameter of 5.4 nm.     

AFM analysis of C60 and a poly(amido amine) dendrimer-C60 nanoconjugate

Atomic force microscopy (AFM) was used to study the nanoscopic structure and topography of buckminsterfullerene (C60) and a conjugate of C60 with generation four, amine-terminated, poly(amido amine) dendrimer (PAMAM-G4). The conjugate contains a PAMAM-G4 core and C60 shell formed by reacting PAMAM-G4 with an excess of C60. Fractal patterns of C60 were observed in nanoscopic AFM images when solutions of different concentrations of C60 in pyridine or toluene were dried at room temperature. In contrast, no fractal patterns were detected in the AFM images of the dendrimer-C60 nanoconjugate, prepared from pyridine solution in a similar manner. Thus, the C60-shell alone is not sufficient to impart the same fractal patterns on the conjugate.     

Reversible pH manipulation of the fluorescence emission from sectorial poly(amido amine) dendrimers

The first to fourth generation (G1-G4) of sectorial poly(amido amine) (PAMAM) dendrimers with ethanolamine core and amino terminals are synthesized by a divergent route. Blue fluorescence emission from these dendrimers is observed. It is found that there is a remarkable difference in the fluorescence behavior for these different generations of dendrimers. The emission intensity of these dendrimers is almost linearly enhanced along with the increase of their concentrations. A significant pH-dependent profile of the fluorescence intensity is also observed. As the pH value decreases from 8 to 3, the fluorescence intensity increases almost linearly. Furthermore, the fluorescence intensity of the dendrimers shows a reversible behavior depending on pH value within the pH range from 3 to 11. This property enables the reversible manipulation of the fluorescence of these dendrimers by adjusting the pH values, which contributes to a potential application of these materials in fluorescent pH sensors.     

Biodegradable poly(amine-co-ester) terpolymers for targeted gene delivery

Many synthetic polycationic vectors for non-viral gene delivery show high efficiency in vitro, but their usually excessive charge density makes them toxic for in vivo applications. Here we describe the synthesis of a series of high molecular weight terpolymers with low charge density, and show that they exhibit efficient gene delivery, some surpassing the efficiency of the commercial transfection reagents Polyethylenimine and Lipofectamine 2000. The terpolymers were synthesized via enzyme-catalyzed copolymerization of lactone with dialkyl diester and amino diol, and their hydrophobicity adjusted by varying the lactone content and by selecting a lactone comonomer of specific ring size. Targeted delivery of the pro-apoptotic TRAIL gene to tumour xenografts by one of the terpolymers results in significant inhibition of tumour growth, with minimal toxicity both in vitro and in vivo. Our findings suggest that the gene delivery ability of the terpolymers stems from their high molecular weight and increased hydrophobicity, which compensates for their low charge density.     

Influence of highly branched poly(amido amine) on the properties of hyperbranched polyurethane/clay nanocomposites

The fascinating architecture of hyperbranched polymer imparts a truck load of novel properties to the material. Epoxy resin modified Mesua ferrea L. seed oil based hyperbranched polyurethane (MHBPU) nanocomposites were prepared by in situ technique using s-triazine based highly branched poly(amido amine) (HBPAA) modified organo-nanoclay. The HBPAA was synthesized by A₂ + B₃ technique with good yield (>75%) using urea and s-triazine. The formation of the polymer was confirmed with the help of ¹H NMR, FTIR, UV spectroscopic, and measurements of solution viscosity with other physical properties. This HBPAA was successfully utilized to swell the montmorillonite organo-nanoclay as the interlayer gallery distance increases up to 8.2 Å, obtained by XRD study. The FTIR further confirmed the presence of interactions of the HBPAA moiety with the organo-clay layers. The formation of nanocomposites was confirmed by FTIR, XRD, SEM, TEM and rheological studies. The improvements of tensile strength (1.7 times) and scratch hardness (2.3 times) along with the dramatic enhancement of thermostability and flame retardancy without compromising impact resistance, bending, and elongation at break of the nanocomposites compared to pristine MHBPU thermoset are the noticeable credits of the present investigation. The results signify the great potential of the studied materials for various advanced applications.     

Electrical and magnetic properties of electro-oxidative polymerized poly(tris(thienylphenyl)amine)s

Electro-oxidative polymerized poly(tris(thienylphenyl)amine)s, which have the hyperbranched (dendritic) structure (PTPA) and linear type (PMeTPA), were investigated for their electrical and magnetic properties. The conductivity PTPA showed was almost one order higher than that of PMeTPA. From the solid state ESR measurements of the polymers, observation of ESR signal at g = 2.0027 and 2.0030 indicated the formation of a triphenylamine cation radical. The normalized magnetization plots (M/M_s) for PTPA and PMeTPA are close to the theoretical Brillouin curves for S = 1, indicating a magnetic interaction between the spin centers in PMeTPA. The spin concentrations determined by the M_s values of PTPA and PMeTPA were 7.3–7.4 and 1.3–1.4%, respectively. This large difference in the spin concentration of the polymers according to the structure resulted from a different spin conformation by the radical structure.     

O-Carboxymethyl-chitosan/organosilica hybrid nanoparticles as non-viral vectors for gene delivery

Polymeric non-viral vectors, such as chitosan nanoparticles show good biocompatibility, but low transfection efficiency. The objective of this study was to improve the transfection efficiency of chitosan based non-viral vectors by using o-carboxymethyl-chitosan which is a kind of water-soluble chitosan derivative and also has good biocompatibility. O-Carboxymethyl-chitosan-organosilica hybrid nanoparticles (CMG NPs) were synthesized through a rapid one-step aqueous synthetic approach for gene delivery. The size of nanoparticles was 276 ± 25 nm and zeta potential was 31.6 ± 0.4 mV in deionized water. Zeta potential increased with the decrease of pH, and it had been discovered that pH = 5.5 is the best point for CMG NPs to bond with plasmid DNA. DNA inclusion and integrity was evaluated by gel electrophoresis, and it is indicated that CMG NPs could protect DNA against DNase I and serum degradation. The results of MTT for cell viability and in vitro transfection also support the idea that CMG NPs could be used as efficient and safe vectors for gene delivery.     

Polyethylenimine functionalized magnetic nanoparticles as a potential non-viral vector for gene delivery

Polyethylenimine (PEI) functionalized magnetic nanoparticles were synthesized as a potential non-viral vector for gene delivery. The nanoparticles could provide the magnetic-targeting, and the cationic polymer PEI could condense DNA and avoid in vitro barriers. The magnetic nanoparticles were characterized by Fourier transform infrared spectroscopy, X-ray powder diffraction, dynamic light scattering measurements, transmission electron microscopy, vibrating sample magnetometer and atomic force microscopy. Agarose gel electrophoresis was used to asses DNA binding and perform a DNase I protection assay. The Alamar blue assay was used to evaluate negative effects on the metabolic activity of cells incubated with PEI modified magnetic nanoparticles and their complexes with DNA both in the presence or absence of an external magnetic field. Flow cytometry and fluorescent microscopy were also performed to investigate the transfection efficiency of the DNA-loaded magnetic nanoparticles in A549 and B16-F10 tumor cells with (+M) or without (?M) the magnetic field. The in vitro transfection efficiency of magnetic nanoparticles was improved obviously in a permanent magnetic field. Therefore, the magnetic nanoparticles show considerable potential as nanocarriers for gene delivery.     

Nano-sized calcium phosphate (CaP) carriers for non-viral gene deilvery

Gene therapy has garnered much interest due to the potential for curing multiple inherited and/or increases in the acquired diseases. As a result, there has been intense activity from multiple research groups for developing effective delivery methods and carriers, which is a critical step in advancing gene delivery technologies. In order for the carriers to effectively deliver the genetic payloads, multiple extracellular and intracellular barriers need to be overcome. Although overcoming these challenges to improve the effectiveness is critical, the development of safe gene delivery agents is even more vital to assure its use in clinical applications. The development of safe and effective strategies has therefore been a major challenge impeding gene therapy progress. In this regard, calcium phosphate (CaP) based nano-particles has been considered as one of the candidate non-viral gene delivery vehicles, but has been plagued by inconsistent and low transfection efficiencies limiting its progress. There has been major research effort to improve the consistency and effectiveness of CaP based vectors. Currently, it is therefore thought that by controlling the various synthesis factors such as Ca/P ratio, mode of mixing, and type of calcium phosphate phase, such variability and inefficiency could be modulated. This review attempts to provide a comprehensive analysis of the current research activity in the development of CaP based ceramic and polymer-ceramic hybrid systems for non-viral gene delivery. Preliminary transfection results of hydroxyapatite (HA or NanoCaPs), amorphous calcium phosphate (ACP) and brushite phases are also compared to assess the effect of various CaP phases, and correspondingly, changes in the dissolution characteristic of the pDNA-CaP complex on the gene transfection efficiency.     

Structural characterization of novel gemini non-viral DNA delivery systems for cutaneous gene therapy

The structural and physicochemical properties of novel cationic lipid-based DNA complexes have been investigated for the purpose of designing micro/nano-scale self-assembling delivery systems for cutaneous gene therapy. DNA/gemini surfactant (spacer n?=?3–16; chain m?=?12 or 16) complexes (1?:?10 charge ratio), with or without dioleoylphosphatidyl-ethanolamine (DOPE), designed for cellular transfection, were generally in the range of 100–200?nm as demonstrated by atomic force microscopy and particle size analysis. Small-angle X-ray scattering measurements indicated that the DNA/gemini complexes lacked long-range order, whereas DNA/gemini/DOPE complexes exhibited lamellar and polymorphic phases other than hexagonal. Correlation studies using transfection efficiency data in PAM 212 keratinocytes and in vitro skin absorption indicated that formulations containing gemini surfactants having the ability to induce structures other than lamellar in the resulting complexes, generally exhibited greater transfection activity and cutaneous absorption.     

Characterizing poly(epsilon-caprolactone)-b-chitooligosaccharide-b-poly(ethylene glycol) (PCP) copolymer micelles for doxorubicin (DOX) delivery: effects of crosslinked of amine groups

New amine-groups containing tri-block copolymers and micelles that consisting of poly(epsilon-caprolactone)-b-chitooligosaccharide-b-poly(ethylene glycol) (PCL-b-COS-b-PEG, PCP), were synthesized, characterized, and evaluated for delivering doxorubicin (DOX) with or without crosslinked amine groups by genipin. The characteristics of the PCP copolymers of Fourier-transform infrared spectrometry (FT-IR) verify the amine and ester groups of the COS and the PCL of the copolymers, respectively. 1H nuclear magnetic resonance (1H NMR) spectra verify the structures of the PCP copolymers consisting two PCL and PEG polymers reacted onto the COS block. In addition, gel permeation chromatography (GPC) determines the number average molecular weight of the tri-block copolymers (Mn) of approximately 11340 Da/mole. The PCP copolymers can self-assemble to form polymeric micelles at the critical micelle concentration (CMC) of 1.0 microM as determined by the UV-VIS absorption spectra. The mean diameter of the PCP micelles is 90 nm, as determined using a dynamic light-scattering (DLS) analyzer. Moreover, the zeta potentials of PCP micelles change from neutral to cationic state when pH of suspension mediums varied from 7.4 to 3.0. For evaluating delivery characteristics of hydrophobic DOX, it was loaded into PCP micelles with or without crosslinked by genipin. The burst release and release period of DOX for the crosslinked micelles are significantly reduced (P < 0.003, n = 3, for pH = 7.4) and sustained (e.g., 8 days), respectively, than those non-crosslinked ones (e.g., 4 days). In conclusion, new tri-block amine groups containing PCP copolymers are synthesized that can self-assemble as PCP micelles. After post-crosslinked amine groups of DOX loaded the micelles, they can effectively reduce the burst release and sustain the release of DOX at different pH dissolution mediums. Further applications of PCP copolymers and micelles for drug delivery can be explored in future.     

Kidney-specific peptide-conjugated poly(ester amine) for the treatment of kidney fibrosis

Kidney gene therapy using the hepatocyte growth factor (HGF) gene may offer new strategies for the treatment of chronic renal disease such as kidney fibrosis, because HGF has the potential to promote tubular repair and to inhibit tissue fibrosis. As a non-viral vector for gene delivery, polyethylenimine (PEI) exhibits high gene expression due to its buffering capacity with cytotoxicity, although its cytotoxicity depends on its molecular weight. In this study, to minimize the cytotoxicity of PEI with a high transfection efficiency, biodegradable poly(ester amine) (PEA) based on glycerol dimethacrylate (GDM) and low molecular weight PEI (LMW PEI) was synthesized and kidney targeting peptide was conjugated to the PEA (PEP-PEA) to give it kidney cell specificity. The PEP-PEA showed good physicochemical properties as a gene delivery carrier, such as DNA condensation ability, protection of the DNA in the complexes from enzyme degradation, and formation of nanosized complexes with spherical shapes. Higher transfection efficiency in 293T cells was achieved with the PEP-PEA than with the PEA and the PEI 25 kDa with lower cytotoxicity. Also, the HGF gene that was complexed with the PEP-PEA was specifically delivered to the obstructed kidney in the unilateral ureteral obstruction (UUO) model rats. The delivered HGF gene exhibited potency in recovering renal functions, which indicates the potential of the PEP-PEA as a safe and efficient carrier for the treatment of kidney fibrosis.     

Amphiphilic zwitterionic poly(dimethylsiloxane) (PDMS)-contained poly(ether amine) (Z-SiPEA) as the responsive polymeric dispersant

We demonstrated here a novel concept of the responsive dispersant based on the amphiphilic zwitterionic poly(ether amine) (Z-SiPEAs), which can control the dispersion of dyes and pigments in water. Z-SiPEAs are composed of short poly (dimethylsiloxane) (PDMS) chain in the backbone and Jeffamine L100 as graft chain. The amino groups in the backbone and carboxyl groups grafted to the backbone make the obtained Z-SiPEAs zwitterionic. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) results revealed that the obtained Z-SiPEAs can self-assemble into nanoparticles in water, which possessed sharp response to temperature, pH, and ionic strength with the tunable clouding point (CP). In the presence of Z-SiPEAs, not only hydrophobic dyes such as Nile Red can be dispersed in water, but the hydrophilic dye Rose Bengal (RB) can be dispersed in unpolar solvents. Further more, Z-SiPEAs can enhance the dispersion of inorganic pigments Titanium White, Iron Red and Chrome Yellow very efficiently in most solvents. It should be noted that the dispersion of organic dyes and inorganic pigments in water can be controlled by temperature in the presence of Z-SiPEAs. 1H NMR and FT-IR revealed the strong coordination between carboxyl groups in Z-SiPEAs and metal atoms of inorganic pigments. These characteristics will give Z-SiPEAs potential as the novel responsive polymeric dispersant.     

Electrospinning of novel biodegradable poly(ester urethane)s and poly(ester urethane urea)s for soft tissue-engineering applications

The development of biomimetic highly-porous scaffolds is essential for successful tissue engineering. Segmented poly(ester urethane)s and poly(ester urethane urea)s have been infrequently used for the fabrication of electrospun nanofibrous tissues, which is surprising because these polymers represent a very large variety of materials with tailored properties. This study reports the preparation of new electrospun elastomeric polyurethane scaffolds. Two novel segmented polyurethanes (SPU), synthesized from poly(ε-caprolactone) diol, 1,6-hexamethylene diisocyanate, and diester-diphenol or diurea-diol chain extenders, were used (Caracciolo et al. in J Mater Sci Mater Med 20:145–155, 2009). The spinnability and the morphology of the electrospun SPU scaffolds were investigated and discussed. The electrospinning parameters such as solution properties (polymer concentration and solvent) and processing parameters (applied electric field, needle to collector distance and solution flow rate) were optimized to achieve smooth, uniform bead-free fibers with diameter (~700 nm) mimicking the protein fibers of native extracellular matrix (ECM). The obtained elastomeric polyurethane scaffolds could be appropriate for soft tissue-engineering applications.     

Hydrophilic/lipophilic N-methylene phosphonic chitosan as a promising non-viral vector for gene delivery

Cationic amphiphilic drugs have recently been shown to inhibit receptor recycling by disrupting the assembly–disassembly of clathrin at the plasma membrane and endosomes. It is therefore proposed that amphiphilic and cationic polysaccharide macromolecule, when used as gene delivery vectors, may have potential ability to direct the disassembly process of cell membrane organization, and penetrate across the cell membrane into cell and nucleus. In the current study, N-methylene phosphonic chitosan (NMPCS), an amphiphilic macromolecule, was synthesized by incorporating the methylene phosphonic group into the amino groups of chitosan (CS) using formaldehyde as the coupling agent, and characterized with a FTIR spectrometer. NMPCS/DNA or CS/DNA complexes were prepared using a complex coacervation method, and characterized by agarose gel electrophoresis retardation assay and dynamic light scattering (DLS). MTT assay was employed to evaluate the cytotoxicity of the polymers and pGL3-control luciferase plasmid was utilized as a reporter gene to assess the transgenic efficacy of the polymers. It was demonstrated that NMPCS was able to fully entrap the DNA at N/P ratio of 2:1, whereas CS entrapped the DNA completely at N/P ratio of 1:1. DLS showed that the NMPCS/DNA or CS/DNA complexes were of mean diameters ranging from 110 to 180 nm. Neither NMPCS nor CS induced significant loss of cell viability at the concentrations ranging from 1 to 50 μg/ml, whereas PEI at 5 μg/ml started to result in significantly decreased cell viability. The expression of transgene mediated by NMPCS was much higher (more than 100-folds) than that mediated by CS, indicating that NMPCS was a more efficacious gene ferrying vector than CS.     

Transferrin-mediated PEGylated nanoparticles for delivery of DNA/PLL

The purpose of this work was to determine the stability of pDNA/poly(L-lysine) complex (DNA/PLL) during microencapsulation, prepare transferrin (TF) conjugated PEGylated nanoparticles (TF-PEG-NP) loading DNA/PLL, and assess its physicochemical characteristics and in vitro transfection efficiency. The DNA/PLL was prepared by mixing plasmid DNA (pDNA) in deionized water with various amounts of PLL. PEGylated nanoparticles (PEG-NP) loading DNA/PLL were prepared by a water-oil-water double emulsion solvent evaporation technique. TF-PEG-NP was prepared by coupling TF with PEG-NP. The physicochemical characteristics of TF-PEG-NP and in vitro transfection efficiency on K562 cells were measured. The results showed that free pDNA reserved its double supercoiled form (dsDNA) for only on average 25.7% after sonification, but over 70% of dsDNA was reserved after pDNA was contracted with PLL. The particle size range of TF-PEG-NP loading DNA/PLL was 150-450?nm with entrapment efficiency over 70%. TF-PEG-NP exhibited the low burst effect (<10%) within 1 day. After the first phase, DNA/PLL displayed a sustained release. The amount of cumulated DNA/PLL release from TF-PEG-NP with 2% polymer over 7 days was 85.4% for DNA/PLL (1:0.3 mass ratio), 59.8% and 43.1% for DNA/PLL (1:0.6) and DNA/PLL (1:1.0), respectively. To TF-PEG-NP loading DNA/PLL without chloroquine, the percentage of EGFP expressing cells was 28.9% for complexes consisting of DNA/PLL (1:0.3), 38.5% and 39.7% for DNA/PLL (1:0.6) and DNA/PLL (1:1.0), respectively. In TF-PEG-NP loading DNA/PLL with chloroquine, more cells were transfected, the percentage of positive cells was 37.6% (DNA/PLL, 1:0.3), 47.1% (DNA/PLL, 1:0.6) and 45.8% (DNA/PLL, 1:1.0), which meant that the transfection efficiency of pDNA was increased by over 50 times when PLL and TF-PEG-NP were jointly used as a plasmid DNA carrier, in particular, the maximal percentage of positive cells (47.1%) from TF-PEG-NP loading DNA/PLL (1:0.6) was about 70 times the transfection efficiency of free plasmid DNA. The average cell viability of TF-PEG-NP loading DNA/PLL was about 90%, which meant that TF-PEG-NP appeared to be safer than PLL alone. As a result, TF-PEG-NP loading DNA/PLL could be a more effective non-viral vector for the delivery of pDNA.     

Polyethyleneimine modified biocompatible poly(N-isopropylacrylamide)-based nanogels for drug delivery

A series of biocompatible and stimuli-sensitive poly(N-isopropylacrylamide-co-propyl acrylic acid) (P(NIPAAm-co-PAAc)) nanogels were synthesized by emulsion polymerization. In addition, polyethyleneimine (PEI) was further grafted to modify the PNIPAAm-based nanogels. The P(NIPAAm-co-PAAc)-g-PEI nanogels exhibited good thermosensitivity as well as pH sensitivity. Transmission electron microscopy (TEM) showed that the P(NIPAAm-co-PAAc)-g-PEI and P(NIPAAm-co-PAAc) nanogels displayed well dispersed spherical morphology. The mean sizes of the nanogels measured by dynamic light scattering (DLS) were from 100 nm to 500 nm at different temperatures. The cytotoxicity study indicated P(NIPAAm-co-PAAc) nanogels exhibited a better biocompatibility than both PNIPAAm nanogel and P(NIPAAm-co-PAAc)-g-PEI nanogel although all the three kinds of nanogels did not exhibit apparent cytotoxicity. The drug-loaded nanogels, especially the PEI-grafted nanogels, showed temperature-trigged controlled release behaviors, indicating the potential applications as an intelligent drug delivery system.     

Investigation of swellable poly (N-isopropylacrylamide) based hydrogels for drug delivery

The thermo-sensitive properties of poly (N-isopropylacrylamide) (PNIPA) hydrogels are modified by the addition of hydrophilic acrylamide comonomers and an interpenetrating network of sodium alginate for drug delivery applications near 37 °C. A mathematical model is presented to describe the mass transport kinetics during the hydrogel drug delivery process, which is accompanied by a volume change during phase transition. In this model, the transport in the polymer matrix is described by Fick's second law in cylindrical coordinates, with concentration dependent diffusion coefficients. The moving boundary problems caused by the polymer matrix swelling are also solved by numerical simulation. The models show that the Trypan blue release from the modified PNIPA-based hydrogels is strongly concentration dependent. The sodium alginate component is also shown to effectively facilitate the diffusion process. The results from the simulation are in good agreement with the measurements of diffusion and swelling observed from in vitro experiments. The implications of this work are also discussed for practical drug delivery systems.     

Thermosensitive Y-shaped micelles of poly(oleic acid-Y-N-isopropylacrylamide) for drug delivery

A novel thermosensitive amphiphilic copolymer comprised of two hydrophobic poly(oleic acid) (POA) segments and one hydrophilic poly(N-isopropylacrylamide) (PNIPAAm) segment was designed and synthesized. The structure of the copolymer was confirmed as Y-shaped by FTIR, 1H NMR, and SEC-MALLS analysis. A cytotoxicity study shows that the P(OA-Y-NIPAAm) copolymer exhibits good biocompatibility. The copolymer may self-assemble into micelles in water, with the hydrophobic POA segments at the cores of micelles and the hydrophilic PNIPAAm segments as the outer shells. The resulting micelles demonstrate temperature sensitivity with a lower critical solution temperature (LCST) of 31.5 degrees C and a critical micelle concentration (CMC) of 12.6 mg L(-1). Transmission electron microscopy (TEM) shows that the micelles exhibit a nanospheric morphology within a narrow size range of approximately 10-30 nm. A study of controlled release reveals that the self-assembled micelles have great potential as drug carriers.