The effect of polymer architecture on the nano self-assemblies based on novel comb-shaped amphiphilic poly(allylamine)

Twelve novel poly(allylamine) (PAA)-based, comb-shaped amphiphilic polymers have been developed. Hydrophobic groups of cetyl, palmitoyl and cholesteryl were randomly grafted to PAA and quaternisation was carried out on some modified polymers. Polymers were characterised using ¹H NMR, elemental analysis and differential scanning calorimetry. All polymers formed nano self-assemblies in the aqueous solution with a positive zeta potential and were able to encapsulate a hydrophobic agent, methyl orange, in the core. The critical aggregation concentration (CAC) and the microviscosity were found to be dependent on the polymer hydrophobicity. Being the most hydrophobic polymer, cholesteryl-grafted PAA had the lowest CAC (0.02 mg mL⁻¹) and the highest microviscosity. They appeared to form dense nanoparticles and were transformed into novel nanostructures in the presence of free cholesterol. Palmitoyl-grafted polymers formed nanoparticles while cetyl-grafted polymers formed polymeric micelles. The flexibility of cetyl chains possibly resulted in the formation of multicore polymeric micelles.     

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.     

Bionanoparticles of amphiphilic copolymers polyacrylate bearing cholesterol and ascorbate for drug delivery

In this study, a series of amphiphilic polymers with poly(ascorbyl acrylate) (PAAA) as hydrophilic blocks and polyacrylate bearing side-chain cholesteryl mesogens (PCholDEGA) as hydrophobic blocks were prepared using a combination of four-step reactions consisting of two consecutive reversible addition-fragmentation chain transfer (RAFT), desulfurization, and hydrogenolysis under normal pressure. The thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) as well as wide-angle X-ray diffraction (WAXD) studies showed that the copolymers with PCholDEGA as major block had relatively high stability and clear isotropization temperature (T(i)). Small-angle X-ray diffraction (SAXD) investigation exhibited that the copolymers had bilayer smectic A structure. Their self-assembly behavior was monitored by turbidity change using UV-vis spectrometer, and the morphology and size of the nanoparticles via self-assembly were detected using transmission electron microscopy (TEM) and dynamic light scattering (DLS). The entrapment efficiency and loading capacity of these amphiphilic copolymers were investigated using nile red and drug molecule Ibuprofen. These polymeric micelles with PAAA shell extending into the aqueous solution and strong hydrophobic PCholDEGA core have potential abilities to act as promising nanovehicles with high loading and targeting delivery.     

聚(辛二酸-四甘醇酯)的合成及其微相分离结构的研究

通过熔融缩聚合成了一种新型的两亲性聚酯——聚(辛二酸-四甘醇酯)(PTEGSub),利用GPC,NMR,FTIR,TG,DSC等手段对聚合物的结构进行了表征.研究发现,在25℃时,PTEGSub在水中可以形成胶束,粒径主要集中在20～120nm之间,其临界胶束浓度(CMC)随分子量的升高而降低.通过TEM观察了在选择性溶剂中的胶束形态.利用AFM研究了PTEGSub的微相分离,发现聚合物膜中存在有球状的相分离结构.     

Preparation of polymer nanoparticles by self-assembling of amphiphilic poly-<Emphasis Type="Italic">N</Emphasis>-vinylpyrrolidone derivatives in aqueous media

Amphiphilic N-vinylpyrrolidone polymers were prepared by a new one-step procedure consisting in radical polymerization of the monomer in the presence of long-chain monobasic saturated carboxylic acid chlorides as chain-transfer and chain-terminating agents. The behavior of the new amphiphilic polymers differing in the structure of the hydrophilic and hydrophobic moieties in aqueous media was studied. The synthesized polymers at definite concentrations undergo spontaneous aggregation with the formation of spherical nanosized micellar particles consisting of a hydrophobic core and a hydrophilic shell. The main characteristics of the polymer nanoparticles formed were determined, and the possibility of using them as promising carriers for the delivery of biologically active compounds and drugs was revealed.     

Fully biodegradable polymeric micelles based on hydrophobic‐ and hydrophilic‐functionalized poly(lactide) block copolymers

Novel amphiphilic diblock copolymers from a combination of hydrophobic‐functional poly(lactides) (PLAs) with hydrophilic‐functional PLAs or poly(malic acid), respectively, toward fully biodegradable materials for medical applications, such as micellar drug delivery systems, are reported for the first time. The presented PLA‐based polymeric micelles are characterized by their small size below 100 nm, low critical micellar concentrations, good in vitro stabilities at room and body temperature, and efficient incorporation capability of hydrophobic compounds, particularly with regard to potential drug substances. Moreover, the advantage of being totally degradable with different rates at different pH values, as investigated in medical cancer treatment, is demonstrated. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3244–3254, 2010     

Innovative amphiphilic cellulose nanobiostructures: Physicochemical,spectroscopic, morphological,and hydrophilic/lipophilic properties

The amphiphilic character of cellulosic copolymers offers the opportunity to employ their derivatives as novel bio-friendly stable amphiphilic agents. It can be speculated that the synthesized nanobiostructures with hydrophilic and hydrophobic segments will have micellar features. Our investigations, for the first time, demonstrate that the amphiphilic nature of the synthesized macromolecules based on hydrophobic cellulose triacetate (CTA) and hydroxyl terminated oligomeric species of CTA (HCTA) by using hydrophilic polyethylene glycol (PEG) with M_n 600 and 2000 D as CTA-g-PEG, 600; CTA-g-PEG, 2000; HCTA-b-PEG, 600; and HCTA-b-PEG, 2000. The characteristic features of the copolymers were determined by XRD, differential scanning calorimeter, ¹H NMR, FTIR, GPC, dynamic light scattering measurements, and transmission electron microscopy. In addition, their critical micelle concentrations were evaluated. The obtained results indicated that the hydrophobic blocks make a significant influence on the micellar characteristics of the surfactants. A comparison of the micellar behavior of a hydrophobic species, like pyrene, incorporated in the synthesized systems indicated that the incorporation content of the surfactants is influenced by the hydrophobic and hydrophilic chain lengths. Therefore, it is possible to design the diversity of the surfactants based on various hydrophilic/lipophilic balance.     

Amphiphilic poly-n-vinyl-2-pyrrolidone: Synthesis,properties, nanoparticles

Water-soluble amphiphilic polymers based on N-vinyl-2-pyrrolidone (Amph-PVP) have been synthesized. Amphiphilic diblock polymers have been obtained via a single-step technique. For the synthesized amphiphilic polymers, the critical concentrations of mycelium formation (CCM) have been determined. The structure of the polymers obtained was confirmed by IR and NMR spectroscopy. The critical concentration of micelle formation (CCM) for the synthesized polymers has been found to be in the micromolar range. The fluorescent dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (Dil) was chosen as a model substance for the synthesis of nanoparticles. Micellar particles were obtained via an ultrasonic technique followed by evaporation of the organic solvent (emulsion method).     

Polymeric Nanovectors Incorporated with Ganciclovir and HSV-tk Encoding Plasmid for Gene-Directed Enzyme Prodrug Therapy

In the area of gene-directed enzyme prodrug therapy (GDEPT), using herpes simplex virus thymidine kinase (HSV-tk) paired with prodrug ganciclovir (GCV) for cancer treatment has been extensively studied. It is a process involved with two steps whereby the gene (HSV-tk) is first delivered to malignant cells. Afterward, non-toxic GCV is administered to that site and activated to cytotoxic ganciclovir triphosphate by HSV-tk enzyme expressed exogenously. In this study, we presented a one-step approach that both gene and prodrug were delivered at the same time by incorporating them with polymeric micellar nanovectors. GCV was employed as an initiator in the ring-opening polymerization of ε-caprolactone (ε-CL) to synthesize hydrophobic GCV-poly(caprolactone) (GCV–PCL), which was furthered grafted with hydrophilic chitosan to obtain amphiphilic polymer (GCV–PCL–chitosan) for the fabrication of self-assembled micellar nanoparticles. The synthesized amphiphilic polymer was characterized using Fourier transform infrared spectroscopy and proton nuclear magnetic resonance. Micellar prodrug nanoparticles were analyzed by dynamic light scattering, zeta potential, critical micelle concentration, and transmission electron microscopy. Polymeric prodrug micelles with optimal features incorporated with HSV-tk encoding plasmids were cultivated with HT29 colorectal cancer cells and anticancer effectiveness was determined. Our results showed that prodrug GCV and HSV-tk cDNA encoded plasmid incorporated in GCV–PCL–chitosan polymeric nanocarriers could be delivered in a one-step manner to HT-29 cells and triggered high cytotoxicity.     

Polymeric micelle systems of hydroxycamptothecin based on amphiphilic N-alkyl-N-trimethyl chitosan derivatives

This research investigated the possible utilization of amphiphilic N-octyl-N-trimethyl chitosan (OTMCS) derivatives in solublization and controlled release of 10-hydroxycamptothecin (10-HCPT), a hydrophobic anticancer drug. The release behavior of the 10-HCPT-OTMCS micelles was measured and compared to that of a commercial 10-HCPT lyophilized powder in vitro and in vivo. This research also examined the effects of chemical structure of the chitosan derivatives and the micellar preparation conditions on the encapsulation efficiency, drug loading content, and particle size of the polymeric micelles. The results showed that these chitosan derivatives were able to self-assemble and form spherical shape polymeric micelles with an average particle size range of 24–280 nm and a drug loading content of 4.1–32.5%, depending on the modified structures and loading procedures. The solubility of 10-HCPT in aqueous fluid was increased about 80,000-fold from 2 ng/ml in water to 1.9 mg/ml in OTMCS micellar (degree of octyl and trimethyl substitution is 8% and 54%, respectively) solution. In addition, OTMCS was able to modulate the in vitro release of 10-HCPT and improve its pharmacokinetic properties and lactone ring stability in vivo. These data suggested the possible utilization of the amphiphilic micellar chitosan derivatives as carriers for hydrophobic drugs for improving their delivery and release properties.     

Drug-loaded and superparamagnetic iron oxide nanoparticle surface-embedded amphiphilic block copolymer micelles for integrated chemotherapeutic drug delivery and MR imaging

We report on the fabrication of organic/inorganic hybrid micelles of amphiphilic block copolymers physically encapsulated with hydrophobic drugs within micellar cores and stably embedded with superparamagnetic iron oxide (SPIO) nanoparticles within hydrophilic coronas, which possess integrated functions of chemotherapeutic drug delivery and magnetic resonance (MR) imaging contrast enhancement. Poly(ε-caprolactone)-b-poly(glycerol monomethacrylate), PCL-b-PGMA, and PCL-b-P(OEGMA-co-FA) amphiphilic block copolymers were synthesized at first by combining ring-opening polymerization (ROP), atom transfer radical polymerization (ATRP), and post- modification techniques, where OEGMA and FA are oligo(ethylene glycol) monomethyl ether methacrylate and folic acid-bearing moieties, respectively. A model hydrophobic anticancer drug, paclitaxel (PTX), and 4 nm SPIO nanoparticles were then loaded into micellar cores and hydrophilic coronas, respectively, of mixed micelles fabricated from PCL-b-PGMA and PCL-b-P(OEGMA-co-FA) diblock copolymers by taking advantage of the hydrophobicity of micellar cores and strong affinity between 1,2-diol moieties in PGMA and Fe atoms at the surface of SPIO nanoparticles. The controlled and sustained release of PTX from hybrid micelles was achieved, exhibiting a cumulative release of ~61% encapsulated drugs (loading content, 8.5 w/w%) over ~130 h. Compared to that of surfactant-stabilized single SPIO nanoparticles (r(2) = 28.3 s(-1) mM(-1) Fe), the clustering of SPIO nanoparticles within micellar coronas led to considerably enhanced T(2) relaxivity (r(2) = 121.1 s(-1) mM(-1) Fe), suggesting that hybrid micelles can serve as a T(2)-weighted MR imaging contrast enhancer with improved performance. Moreover, preliminary experiments of in vivo MR imaging were also conducted. These results indicate that amphiphilic block copolymer micelles surface embedded with SPIO nanoparticles at the hydrophilic corona can act as a new generation of nanoplatform integrating targeted drug delivery, controlled release, and disease diagnostic functions.     

Thermoresponsive amphiphilic symmetrical triblock copolymers with a hydrophilic middle block made of poly(N-isopropylacrylamide): synthesis, self-organization, and hydrogel formation

Several series of symmetrical triblock copolymers were synthesized by the reversible addition fragmentation chain transfer method. They consist of a long block of poly(N-isopropylacrylamide) as hydrophilic, thermoresponsive middle block, which is end-capped by two small strongly hydrophobic blocks made from five different vinyl polymers. The association of the amphiphilic polymers was studied in dilute and concentrated aqueous solution. The polymer micelles found at low concentrations form hydrogels at high concentrations, typically above 30–35 wt.%. Hydrogel formation and the thermosensitive rheological behavior were studied exemplarily for copolymers with hydrophobic blocks of polystyrene, poly(2-ethylhexyl acrylate), and poly(n-octadecyl acrylate). All systems exhibited a cloud point around 30 °C. Heating beyond the cloud point initially favors hydrogel formation but continued heating results in macroscopic phase separation. The rheological behavior suggests that the copolymers associate into flower-like micelles, with only a small share of polymers that bridge the micelles and act as physical cross-linkers, even at high concentrations.     

Research on association between multi-sticker amphiphilic polymer and water-soluble β-cyclodextrin polymer

The host cyclodextrin polymer-P(AM/A-β-CD/NaA) is prepared by redox free-radical copolymerization. Additionally, the multi-sticker amphiphilic polymer-P(AM/BHAM/NaA) as a guest polymer is synthesized using micellar polymerization. The copolymer structures are characterized by ¹H NMR. Subsequently, all the polymers and inclusion complexes are evaluated in terms of apparent viscosity, optical absorption spectra and rheological property. The results indicate that the inclusion association between the cyclodextrin group (CD) and multi-sticker hydrophobic monomer (BHAM) is in accordance with ternary interaction (CD/BHAM?=?2:1). Because of the inclusion association between the host and guest polymers, the solution of inclusion complex has much higher viscoelasticity even under the low amphiphilic polymer concentration. When the molar ratio of CD to BHAM is 1:1, the critical aggregation concentration (CAC) of the inclusion complex solution still remains. Furthermore, above the CAC, two types of associations, inclusion association and inter-molecular hydrophobic association, can occur in the complex solution and these interactions were also verified by fluorescence spectroscopy and atomic force microscopy (AFM). In this paper, the inclusion rule of cyclodextrin polymer with the multi-sticker amphiphilic polymer is discussed, and the rule of the enhanced solution viscosity is further explored.     

Synthesis of Y-shaped poly(solketal acrylate)-containing block copolymers and study on the thermoresponsive behavior for micellar aggregates

One novel type of Y-shaped amphiphilic copolymers with two hydrophobic poly(solketal acrylate) (PSA) branches and one hydrophilic monomethoxy poly(ethylene glycol) (MPEG) block was synthesized by atom transfer radical polymerization (ATRP). These Y-shaped polymers can disperse in aqueous media to self-assemble into micellar aggregates with a spherical core-shell structure. The aqueous copolymer solutions exhibited transmittancy transition in the temperature range of 30-60 °C via optical transmittance measurements. An interesting thermo-dependent size of the micellar aggregates was observed by dynamic light scattering techniques and transmission electron microscopy, which showed that the micelle diameters were decreased with temperature increasing. The nile red release from the micelles at 25 °C and 37 °C under various pHs showed that temperature has great influence on release behavior. With good biocompatibility, the micellar aggregates formed from MPEG-block-(PSA)(2) may serve as one promising thermosensitive nanovehicle for targeted drug delivery.     

Novel PEGylated Amphiphilic Copolymers as Nanocarriers for Drug Delivery: Synthesis,Characterization and Curcumin Encapsulation

Amphiphilic polymers can self assemble into micellar nano-particles and can be effectively used as nano carriers for drug delivery. A number of macromolecular delivery systems are under investigation to improve the efficacy of prospective drugs. In this study, seven new co-polymers were synthesized under mild reaction conditions in bulk (without solvent) by chemoenzymatic approach using Candida antarctica lipase (Novozyme 435) and molecular sieves, subsequently these polymers were treated with different long chain bromoalkanes and acid chlorides for attachment of the lipophilic moieties to the backbone polymer via an ether or an ester linkage, respectively in order to make them amphiphilic. These synthesized nano-particles demonstrated high drug loading capacity and have the potential to encapsulate hydrophobic drugs.     

Synthesis,surface accumulation,and micellar properties of amphiphilic block copolymers

Amphiphilic block copolymers, i.e., poly(methyl methacrylate)-b-poly(2-dimethylethylammoniumethyl methacrylate), were synthesized by the reaction between two prepolymers. Carboxyl-terminated poly(methyl methacrylate) and hydroxyl-terminated poly(2-dimethylaminoethyl methacrylate) were prepared by radical polymerization of the corresponding monomers in the presence of thioglycolic acid and 2-mercaptoethanol as a chain transfer agent, respectively. Two condensation methods, i.e., DCC and the acid chloride method, were used for the reactions of these prepolymers. The subsequent quarternization produced the amphiphilic block copolymers. Surface property of poly(methyl methacrylate) films containing this amphiphilic block copolymer was examined by measuring contact angles for water. The addition of only 0.5 wt% of the block copolymer was sufficient to make poly(methyl methacrylate) surfaces hydrophilic. The block copolymer formed a polymeric micelle in acetone–water mixed solvent.     

Water-dispersible, uniform nanospheres by heating-enabled micellization of amphiphilic block copolymers in polar solvents

Uniform nanospheres with tunable size down to 30 nm were prepared simply by heating amphiphilic block copolymers in polar solvents. Unlike reverse micelles prepared in nonpolar, oily solvents, these nanospheres have a hydrophilic surface, giving them good dispersibility in water. Furthermore, they are present as individual, separated, rigid particles upon casting from the solution other than continuous thin films of merged micelles cast from micellar solution in nonpolar solvents. These nanospheres were generated by a heating-enabled micellization process in which the affinity between the solvent and the polymer chains as well as the segmental mobility of both hydrophilic and hydrophobic blocks was enhanced, triggering the micellization of the glassy copolymers in polar solvents. This heating-enabled micellization produces purely well-defined nanospheres without interference of other morphologies. The micelle sizes and corona thickness are tunable mainly by changing the lengths of the hydrophobic and hydrophilic blocks, respectively. The heating-enabled micellization route for the preparation of polymeric nanospheres is extremely simple, and is particularly advantageous in producing rigid, micellar nanospheres from block copolymers with long glassy, hydrophobic blocks which are otherwise difficult to prepare with high efficiency and purity. Furthermore, encapsulation of hydrophobic molecules (e.g., dyes) into micelle cores could be integrated into the heating-enabled micellization, leading to a simple and effective process for dye-labeled nanoparticles and drug carriers.     

Fate of excited probes in micellar systems

This article presents studies on the photophysical and photochemical behavior of probes within micellar systems: organized emulsifier/polymer aggregates; the intra- and interpolymer association of amphiphilic polymers; monomer-swollen micelles (microdroplets); and the interfacial layer. Pyrene (Py) as a probe is particularly attractive because of its ability to measure the polarity of its microenvironment. Dipyme yields information on the microviscosity of micellar systems. Probes such as laurdan and prodan can be used to explore the surface characteristics of micelles or microdroplets. The dansyl group has a special photophysical property that gives information about the local polarity and mobility (viscosity) of the microenvironment. The organized association of amphiphilic polymer and emulsifier introduces a heterogeneity in the local concentration of the reactants. This heterogeneity also results from the attractive interaction between hydrophilic monomer and emulsifier in the case when the monomer carries a positive charge and the counterpart a negative one, and vice versa. Some emulsifiers can bind to the amphiphilic copolymers by simple partitioning between the aqueous phase and the polymer--non-cooperative association. The interaction between micelles (microdroplets) and charged polymers leads to the formation of mixed micelles. Binding emulsifiers to these polymers was detected at emulsifier concentrations much below the critical micellar concentration (CMC). Emulsifiers often interact cooperatively with polymers at the critical aggregation concentration (CAC) below the CMC, forming micelle-like aggregates within the polymer. The CAC can be taken as a measure of interaction between the emulsifier and polymer. A decrease in the monomer fluorescence intensity of probe-labeled polymer results from increased excimer formation, or higher aggregates within the unimolecular polymeric micelles. An increase in the monomer fluorescence intensity of probe-labeled polymer within the micellar system can be ascribed to shielding of the probe chromophores by emulsifier micelles. The quenching of probe emission by (un)charged hydrophilic monomer depends on partitioning of the monomer between the aqueous phase and the micelles. Penetration of reactants into the interfacial layer determines the quenching of the hydrophobic probe by hydrophilic quencher, or vice versa. Quenching depends on the thickness, density and charge of the interfacial layer. Compartmentalization prevents the carbonyl compound and unsaturated monomer from coming into sufficiently close contact to allow singlet or triplet-monomer interaction. All negatively charged carbonyl probe molecules are quenched with significantly lower rates than the parent neutral hydrophobic benzophenone molecules, which were located further inside the aggregates. This results from the different conformation and allocation of reactants within the micellar system. In the reverse micelles, quenching depends on the amount of water in the interfacial layer and the total area of the water/oil interface.     

A series of poly[N-(2-hydroxypropyl)methacrylamide] copolymers with anthracene-derived fluorophores showing aggregation-induced emission properties for bioimaging

A series of new poly[N-(2-hydroxypropyl)methacrylamide]-based amphiphilic copolymers were synthesized through a radical copolymerization of a monomeric/hydrophobic fluorophore possessing aggregation-induced emission (AIE) property with N-(2-hydroxypropyl)methacrylamide. Photophysical properties were investigated using UV-Vis absorbance and fluorescence spectrophotometry. Influences of the polymer structures with different molar ratios of the AIE fluorophores on their photophysical properties were studied. Results show that the AIE fluorophores aggregate in the cores of the micelles formed from the amphiphilic random copolymers and polymers with more hydrophobic AIE fluorophores facilitate stronger aggregations of the AIE segments to obtain higher quantum efficiencies. The polymers reported herein have good water solubility, enabling the application of hydrophobic AIE materials in biological conditions. The polymers were endocytosed by two experimental cell lines, human brain glioblastoma U87MG cells and human esophagus premalignant CP-A, with a distribution into the cytoplasm. The polymers are non-cytotoxic to the two cell lines at a polymer concentration of 1 mg/mL.     

Self-assembled micellar nanoparticles of a novel star copolymer for thermo and pH dual-responsive drug release

An amphiphilic star block copolymer comprised of a hydrophobic PMMA block and a hydrophilic tri-arm poly(NIPAAm-co-DMAEMA) block was synthesized by copolymerization of NIPAAm and DMAEMA, with Ce(4+) ions and tris(hydroxymethyl)methylamine as a redox initiatory system. The star copolymer undergoes self-assembly to the micellar nanoparticles with a core-shell structure and the thermo/pH dual-response, originated from the thermo-sensitivity of PNIPAAm and the pH-sensitivity of PDMAEMA. A fluorescence probe study showed the pH-dependent low CMCs (7.5 to 11.2 mg/L) of the micelles, confirming the formation of stable micelles. Morphological investigations showed that the blank and drug-loaded micelles both had spherical and uniform shapes. The sizes of the blank and drug-loaded nanoparticles were between 80 and 120 nm, depending on the given pH. The LCSTs of the star copolymer were determined to be 32 degrees C, 36.6 degrees C and 39.5 degrees C, corresponding to pH 5, pH 7.4 and pH 9, respectively, demonstrating a pH-dependent thermo-response. As a drug delivery, the micellar nanoparticles showed the dual-responsive release profiles in vitro, which were confirmed by the drug release studies. The obtained results showed the thermo-triggered accelerated release at pH 7.4, and the pH-triggered accelerated release at 37 degrees C, indicating the micelles nanoparticles would be a promising site-specific drug delivery for enhancing the accumulation of drug in targeting pathological areas.