Synthesis and self-assembly behavior of thermoresponsive poly(oligo(ethylene glycol) methyl ether methacrylate)-POSS with tunable lower critical solution temperature

This article reports on the synthesis of a novel amphiphilic polyhedral oligomeric silsesquioxane (POSS) end-capped poly(2-(2-methoxyethoxy)ethyl methacrylate)-co-oligo(ethylene glycol) methacrylate) (POSS-P(MEO₂MA-co-OEGMA)). These thermoresponsive organic–inorganic hybrid polymers exhibit critical phase transition temperature in water, which can be finely tuned by changing the feed ratio of OEGMA and MEO₂MA. The lower critical solution temperature (LCST) of POSS-P(MEO₂MA-co-OEGMA) increases from 31 to 59 °C with the increasing of OEGMA content. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies show that these polymers can self-assemble into spherical micelles with the thermosensitive block into the corona and the POSS forming the core, and larger aggregates are formed when the temperature values are above their LCSTs. These thermoresponsive polymers POSS-P(MEO₂MA-co-OEGMA) with self-assembly behavior and tunable tempetature-responsive property have the potential applications in material science and biotechnology.     

Synthesis and micellization of thermoresponsive galactose‐based diblock copolymers

Thermoresponsive double hydrophilic diblock copolymers poly(2‐(2′‐methoxyethoxy)ethyl methacrylate‐co‐oligo(ethylene glycol) methacrylate)‐b‐poly(6‐O‐methacryloyl‐D ‐galactopyranose) (P(MEO₂MA‐co‐OEGMA)‐b‐PMAGP) with various compositions and molecular weights were obtained by deprotection of amphiphilic diblock copolymers P(MEO₂MA‐co‐OEGMA)‐b‐poly(6‐O‐methacryloyl‐1,2:3,4‐di‐O‐isopropylidene‐D ‐galactopyranose) (P(MEO₂MA‐co‐OEGMA)‐b‐PMAlpGP), which were prepared via reversible addition‐fragmentation chain transfer (RAFT) polymerization using P(MEO₂MA‐co‐OEGMA) as macro‐RAFT agent. Dynamic light scattering and UV–vis studies showed that the micelles self‐assembled from P(MEO₂MA‐co‐OEGMA)‐b‐PMAlpGP were thermoresponsive. A hydrophobic dye Nile Red could be encapsulated by block copolymers P(MEO₂MA‐co‐OEGMA)‐b‐PMAGP upon micellization and released upon dissociation of the formed micelles under different temperatures. The galactose functional groups in the PMAGP block have specific interaction with HepG2 cells, and P(MEO₂MA‐co‐OEGMA)‐b‐PMAGP has potential applications in hepatoma‐targeting drug delivery and biodetection. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Facile preparation of core‐crosslinked micelles from azide‐containing thermoresponsive double hydrophilic diblock copolymer via click chemistry

Double hydrophilic diblock copolymer, poly(N,N‐dimethylacrylamide)‐b‐poly(N‐isopropylacrylamide‐co‐3‐azidopropylacrylamide) (PDMA‐b‐P(NIPAM‐co‐AzPAM), containing azide moieties in one of the blocks was synthesized via consecutive reversible addition‐fragmentation chain transfer polymerization. The obtained diblock copolymer molecularly dissolves in aqueous solution at room temperature, and can further supramolecularly self‐assemble into core‐shell nanoparticles consisting of thermoresponsive P(NIPAM‐co‐AzPAM) cores and water‐soluble PDMA coronas above the lower critical solution temperature of P(NIPAM‐co‐AzPAM) block. As the micelle cores contain reactive azide residues, core crosslinking can be facilely achieved upon addition of difunctional propargyl ether via click chemistry. In an alternate approach in which the PDMA‐b‐P(NIPAM‐co‐AzPAM) diblock copolymer was dissolved in a common organic solvent (DMF), the core‐crosslinked (CCL) micelles can be fabricated via “click” crosslinking upon addition of propargyl ether and subsequent dialysis against water. CCL micelles prepared by the latter approach typically possess larger sizes and broader size distributions, compared with that obtained by the former one. In both cases, the obtained (CCL) micelles possess thermoresponsive cores, and the swelling/shrinking of which can be finely tuned with temperature, rendering them as excellent candidates as intelligent drug nanocarriers. Because of the high efficiency and quite mild conditions of click reactions, we expect that this strategy can be generalized for the structural fixation of other self‐assembled nanostructures. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 860–871, 2008     

Novel thermo‐responsive self‐assembly micelles from a double brush‐shaped PNIPAM‐g‐(PA‐b‐PEG‐b‐PA)‐g‐PNIPAM block copolymer with PNIPAM polymers as side chains

A novel double brush‐shaped copolymer with amphiphilic polyacrylate‐b‐poly(ethylene glycol)‐b‐poly acrylate copolymer (PA‐b‐PEG‐b‐PA) as a backbone and thermosensitive poly(N‐isopropylacrylamide) (PNIPAM) long side chains at both ends of the PEG was synthesized via an atom transfer radical polymerization (ATRP) route, and the structure was confirmed by FTIR, ¹H NMR, and SEC. The thermosensitive self‐assembly behavior was examined via UV‐vis, TEM, DLS, and surface tension measurements, etc. The self‐assembled micelles, with low critical solution temperatures (LCST) of 34–38 ^°C, form irregular fusiform and/or spherical morphologies with single, double, and petaling cores in aqueous solution at room temperature, while above the LCST the micelles took on more regular and smooth spherical shapes with diameter ranges from 45 to 100 nm. The micelle exhibits high stabilities even in simulated physiological media, with low critical micellization concentration (CMC) up to 5.50, 4.89, and 5.05 mg L^?1 in aqueous solution, pH 1.4 and 7.4 PBS solutions, respectively. The TEM and DLS determination reveled that the copolymer micelle had broad size distribution below its LCST while it produces narrow and homogeneous size above the LCST. The cytotoxicity was investigated by MTT assays to elucidate the application potential of the as‐prepared block polymer brushes as drug controlled release vehicles. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis of Thermo‐Responsive Polymers With Both Tunable UCST and LCST

New water‐soluble block copolymers of 2‐(2‐methoxyethoxy)ethyl methacrylate (MEO₂MA), oligo(ethylene glycol) methacrylate (OEGMA), and N‐(3‐(dimethylamino) propyl) methacrylamide (DMAPMA) (poly(OEGMA‐co‐MEO₂MA)‐b‐poly(DMAPMA)) were prepared via sequential reversible addition‐fragmentation chain transfer (RAFT) polymerization. Selective quaternization of poly(DMAPMA) block gives poly(OEGMA‐co‐MEO₂MA)‐b‐poly((3‐[N‐(3‐methacrylamidopropyl)‐N,N‐dimethyl]ammoniopropane sulfonate)‐co‐N‐(3‐(dimethylamino) propyl) methacrylamide), such block copolymer exhibits double thermo‐responsive behavior in water, poly(MEO₂MA‐co‐OEGMA) block shows a lower critical solution temperature (LCST), and poly((3‐[N‐(3‐methacrylamidopropyl)‐N,N‐dimethyl]ammoniopropane sulfonate)‐co‐N‐(3‐(dimethylamino) propyl) methacrylamide) block shows a upper critical solution temperature (UCST). Both of LCST and UCST can be controlled: LCST could be tuned by the fraction of OEGMA units in poly(OEGMA‐co‐MEO₂MA), and UCST was found to be dependent on the degree of quaternization (DQ).

     

Design and proof of reversible micelle‐to‐vesicle multistimuli‐responsive morphological regulations

Multistimuli‐responsive precise morphological control over self‐assembled polymers is of great importance for applications in nanoscience as drug delivery system. A novel pH, photoresponsive, and cyclodextrin‐responsive block copolymer were developed to investigate the reversible morphological transition from micelles to vesicles. The azobenzene‐containing block copolymer poly(ethylene oxide)‐b‐poly(2‐(diethylamino)ethyl methacrylate‐co‐6‐(4‐phenylazo phenoxy)hexyl methacrylate) [PEO‐b‐P(DEAEMA‐co‐PPHMA)] was synthesized by atom transfer radical polymerization. This system can self‐assemble into vesicles in aqueous solution at pH 8. On adjusting the solution pH to 3, there was a transition from vesicles to micelles. The same behavior, that is, transition from vesicles to micelles was also realizable on addition of β‐cyclodextrin (β‐CD) to the PEO‐b‐P(DEAEMA‐co‐PPHMA) solution at pH 8. Furthermore, after β‐CD was added, alternating irradiation of the solution with UV and visible light can also induce the reversible micelle‐to‐vesicle transition because of the photoinduced trans‐to‐cis isomerization of azobenzene units. The multistimuli‐responsive precise morphological changes were studied by laser light scattering, transmission electron microscopy, and UV–vis spectra. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Synthesis,self‐assembly,fluorescence, and thermosensitive properties of star‐shaped amphiphilic copolymers with porphyrin core

Star‐shaped amphiphilic poly(ε‐caprolactone)‐block‐poly(oligo(ethylene glycol) methyl ether methacrylate) with porphyrin core (SPPCL‐b‐POEGMA) was synthesized by combination of ring‐opening polymerization (ROP) and atom transfer radical polymerization (ATRP). Star‐shaped PCL with porphyrin core (SPPCL) was prepared by bulk polymerization of ε‐caprolactone (CL) with tetrahydroxyethyl‐terminated porphyrin initiator and tin 2‐ethylexanote (Sn(Oct)₂) catalyst. SPPCL was converted into SPPCLBr macroinitiator with 2‐bromoisobutyryl bromide. Star‐shaped SPPCL‐b‐POEGMA was obtained via ATRP of oligo(ethylene glycol) methyl ether methacrylate (OEGMA). SPPCL‐b‐POEGMA can easily self‐assemble into micelles in aqueous solution via dialysis method. The formation of micellar aggregates were confirmed by critical micelle formation concentration, dynamic light scattering, and transmission electron microscopy. The micelles also exhibit property of temperature‐induced drug release and the lower critical solution temperature (LCST) was 60.6 °C. Furthermore, SPPCL‐b‐POEGMA micelles can reversibly swell and shrink in response to external temperature. In addition, SPPCL‐b‐POEGMA can present obvious fluorescence. Finally, the controlled drug release of copolymer micelles can be achieved by the change of temperatures. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Hybrid amphiphilic block copolymers containing polyhedral oligomeric silsesquioxane: Synthesis,characterization, and self‐assembly in solutions

In this article, the amphiphilic block copolymers containing polyhedral oligomeric silsesquioxane (POSS), namely PMAPOSS‐b‐PAA and PMAPOSS‐b‐P(AA‐co‐St), were synthesized consecutively by reversible addition–fragmentation chain transfer and selective hydrolysis, and characterized by ¹H NMR, ¹³C NMR, Fourier transform infrared spectroscopy and gel permeation chromatography. In the presence of the nearly gradient styrene distribution along the hydrophilic block with a feed molar ratio of tert‐butyl acrylate (tBA) to St being 10/1, patterned core‐corona nanoparticles (NPs) were formed from the mixture of good/selective solvents (THF/water) by a simple evaporation process at room temperature. With the extending of the co‐block length, the self‐assembled NPs exhibited phase separation behavior of spheres‐dispersed, onion‐like and onion‐cluster hierarchical structures in turn. However, while a change in the feed molar ratio occurred, it resulted in the formation of typical core‐shell micelles (20/1, tBA/St) and disordered particles (5/1, tBA/St), respectively. Furthermore, the self‐assembly behavior of PMAPOSS‐b‐P(AA‐co‐St) in DMF was investigated, which showed that it could perform a mixture morphology of well‐dispersive sphere micelles and large aggregate of micelles. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

A new thermo‐responsive block copolymer with tunable upper critical solution temperature and lower critical solution temperature in the alcohol/water mixture

The multi‐thermo‐responsive block copolymer of poly[2‐(2‐methoxyethoxy)ethyl methacrylate]‐block‐poly[N‐(4‐vinylbenzyl)‐N,N‐diethylamine] (PMEO₂MA‐b‐PVEA) displaying phase transition at both the lower critical solution temperature (LCST) and the upper critical solution temperature (UCST) in the alcohol/water mixture is synthesized by reversible addition‐fragmentation chain transfer polymerization. The poly[2‐(2‐methoxyethoxy)ethyl methacrylate] (PMEO₂MA) block exhibits the UCST phase transition in alcohol and the LCST phase transition in water, while the poly[N‐(4‐vinylbenzyl)‐N,N‐diethylamine] (PVEA) block shows the UCST phase transition in isopropanol and the LCST phase transition in the alcohol/water mixture. Both the polymer molecular weight and the co‐solvent/nonsolvent exert great influence on the LCST or UCST of the block copolymer. By adjusting the solvent character including the water content and the temperature, the block copolymer undergoes multiphase transition at LCST or UCST, and various block copolymer morphologies including inverted micelles, core‐corona micelles, and corona‐collapsed micelles are prepared. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4399–4412     

Synthesis,self‐assembly,and thermosensitivity of amphiphilic POEGMA‐PDMS‐POEGMA triblock copolymers

In this article, the synthesis and self‐assembly of a novel well‐defined biocompatible amphiphilic POEGMA‐PDMS‐POEGMA triblock copolymer were studied. The copolymer was synthesized by atom transfer radical polymerization of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) using α,ω‐dibromo polydimethylsiloxane macroinitiator (Br‐PDMS‐Br). Br‐PDMS‐Br was synthesized through the esterification of α,ω‐hydroxypropyl polydimethylsiloxane and 2‐bromoisobutyryl bromide. The structures of the copolymers were confirmed by proton nuclear magnetic resonance spectroscopy, and gel permeation chromatography. The copolymers showed reversible aggregation in response to temperature cycles with a lower critical solution temperature (LCST) between 61 and 66 °C, as determined by ultraviolet‐visible spectrophotometry and dynamic light scattering. The LCST values increased in proportion to the length of the hydrophilic block and were lower than that of the POEGMA homopolymer. The self‐assembly behavior of the copolymers in aqueous solution was investigated by fluorescence spectroscopy and transmission electron microscopy. The critical micelle concentration value (1.08–0.26 10^?6 mol L^?1) decreased as the length of the POEGMA chain increased. The POEGMA‐PDMS‐POEGMA copolymers can easily self‐assemble into spherical micelles in aqueous solution. Such biocompatible block copolymers may be attractive candidates as ‘‘smart'' thermo‐responsive drug delivery systems. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2684‐2691     

Synthesis,Self‐Assembly,and Multi‐Stimuli Responses of a Supramolecular Block Copolymer

A supramolecular block copolymer is prepared by the molecular recognition of nucleobases between poly(2‐(2‐methoxyethoxy)ethyl methacrylate‐co‐oligo(ethylene glycol) methacrylate)‐SS‐poly(ε‐caprolactone)‐adenine (P(MEO₂MA‐co‐OEGMA)‐SS‐PCL‐A) and uracil‐terminated poly(ethylene glycol) (PEG‐U). Because the block copolymer is linked by the combination of covalent (disulfide bond) and noncovalent (A U) bonds, it not only has similar properties to conventional covalently linked block copolymers but also possesses a dynamic and tunable nature. The copolymer can self‐assemble into micelles with a PCL core and P(MEO₂MA‐co‐OEGMA)/PEG shell. The size and morphologies of the micelles/aggregates can be adjusted by altering the temperature, pH, salt concentration, or adding dithiothreitol (DTT) to the solution. The controlled release of Nile red is achieved at different environmental conditions.

     

K+‐Responsive Block Copolymer Micelles for Targeted Intracellular Drug Delivery

In this work, a novel type of block copolymer micelles with K⁺‐responsive characteristics for targeted intracellular drug delivery is developed. The proposed smart micelles are prepared by self‐assembly of poly(ethylene glycol)‐b‐poly(N‐isopropylacry‐lamide‐co‐benzo‐18‐crown‐6‐acrylamide) (PEG‐b‐P(NIPAM‐co‐B18C6Am)) block copolymers. Prednisolone acetate (PA) is successfully loaded into the micelles as the model drug, with loading content of 4.7 wt%. The PA‐loaded micelles display a significantly boosted drug release in simulated intracellular fluid with a high K⁺ concentration of 150 × 10⁻³m , as compared with that in simulated extracellular fluid. Moreover, the in vitro cell experiments indicate that the fluorescent molecules encapsulated in the micelles can be delivered and specifically released inside the HSC‐T6 and HepG2 cells responding to the increase of K⁺ concentration in intracellular compartments, which confirms the successful endocytosis and efficient K⁺‐induced intracellular release. Such K⁺‐responsive block copolymer micelles are highly potential as new‐generation of smart nanocarriers for targeted intracellular delivery of drugs.     

Construction of temperature responsive hybrid crosslinked self‐assemblies based on PEG‐b‐P(MMA‐co‐MPMA)‐b‐PNIPAAm triblock copolymer: ATRP synthesis and thermoinduced association behavior

A novel amphiphilic thermosensitive poly(ethylene glycol)₄₅‐b‐poly(methyl methacrylate₄₆‐co‐3‐(trimethoxysilyl)propyl methacrylate)₂‐b‐poly(N‐isopropylacrylamide)₄₂₉ (PEG₄₅‐b‐P(MMA₄₆‐co‐MPMA₂)‐b‐PNIPAAm₄₂₉) triblock copolymer was synthesized via consecutive atom transfer radical polymerization techniques. The thermoinduced association behavior of the resulting triblock copolymers in aqueous medium was further investigated in detail by ¹H NMR, transmission electron microscopy, and dynamic light scattering. The results showed that at the temperature (25 °C) below the LCST, PEG₄₅‐b‐P(MMA₄₆‐co‐MPMA₂)‐b‐PNIPAAm₄₂₉ triblock copolymers self‐assembled into the core crosslinked micelles with the hydrophobic P(MMA‐co‐MPMA) block constructing a dense core, protected by the mixed soluble PEG and PNIPAAm chains acting as a hydrophilic shell simultaneously. With an increase in temperature, the resulting core‐shell micelles converted into a new type of micelles with the hydrophilic PEG chains stretching out from the hydrophobic core through the collapsed PNIPAAm shell. On the other hand, at the temperature (40 °C) above the LCST, such triblock copolymers formed the crosslinked vesicles with the hydrophobic PNIPAAm and P(MMA‐co‐MPMA) blocks constructing a membrane core and the soluble PEG chains building the hydrophilic lumen and the shell. On further decreasing the temperature, the resulting vesicles underwent transformation from the shrunken to the expanded status, leading to the formation of swollen vesicles with enlarged size. This study is believed to present the first formation of two types of hybrid crosslinked self‐assemblies by thermoinduced regulation. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Synthesis of chiral amphiphilic diblock copolymers via consecutive RAFT polymerizations and their aggregation behavior in aqueous solution

Two chiral amphiphilic diblock copolymers with different relative lengths of the hydrophobic and hydrophilic blocks, poly(6‐O‐p‐vinylbenzyl‐1,2:3,4‐Di‐O‐isopropylidene‐D ‐galactopyranose)‐b‐poly(N‐isopropylacrylamide) or poly(VBCPG)‐b‐poly(NIPAAM) and poly(20‐(hydroxymethyl)‐pregna‐1,4‐dien‐3‐one methacrylate)‐b‐poly(N‐isopropylacrylamide) or poly(MAC‐HPD)‐b‐poly(NIPAAM) were synthesized via consecutive reversible addition‐fragmentation chain‐transfer polymerizations of VBCPG or MAC‐HPD and NIPAAM. The chemical structures of these diblock copolymers were characterized by ¹H nuclear magnetic resonance spectroscopy. These amphiphilic diblock copolymers could self‐assemble into micelles in aqueous solution, and the morphologies of micelles were investigated by transmission electron microscopy. By comparison with the lower critical solution temperatures (LCST) of poly(NIPAAM) homopolymer in deionized water (32 °C), a higher LCST of the chiral amphiphilic diblock copolymer (poly(VBCPG)‐b‐poly(NIPAAM)) was observed and the LCST increased with the relative length of the poly(VBCPG) block in the copolymer from 35 to 47 °C, respectively. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7690–7701, 2008     

Molecular dynamics simulations of PNIPAM‐co‐PEGMA copolymer hydrophilic to hydrophobic transition in NaCl solution

Classical molecular dynamics simulations were carried out to investigate the hydrophilic to hydrophobic transition of PNIPAM‐co‐PEGMA close to its lower critical solution temperature (LCST) in 1 M NaCl solution. PNIPAM‐co‐PEGMA is a copolymer of poly(N‐isopropylacrylamide) (PNIPAM) and poly(ethylene glycol) methacrylate (PEGMA). The copolymer consists of 38 monomer units of NIPAM with two PEGMA chains attached to the PNIAPM backbone. The PNIPAM‐co‐PEGMA was observed to go through the hydrophilic?hydrophobic conformational change for simulations at temperature slightly above its LCST. Na⁺ ions were found to bind strongly and directly with amide O, even more strongly with the O atoms on PEGAMS chains, whereas Cl^? ions only exhibit weak interaction with the polymer. Significantly a novel caged stable metal‐organic complex involving a Na⁺ ion coordinated by six O atoms from the copolymer was observed after the PNIPAM‐co‐PEGMA copolymer went through conformational transition to form a hydrophobic folded structure. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011     

Synthesis,characterization, and properties of tunable thermosensitive amphiphilic dendrimer‐star copolymers with Y‐shaped arms

Novel and well‐defined amphiphilic dendrimer‐star copolymer poly(ε‐caprolactone)‐block‐(poly(2‐(2‐methoxyethoxy)ethylmethacrylate‐co‐oligo(ethylene glycol) methacrylate))₂ with Y‐shaped arms were synthesized by the combination of ring‐opening polymerization (ROP) and atom transfer radical polymerization (ATRP). The investigation of thermal properties and the analysis of crystalline morphology indicate that the high‐branched structure of dendrimer‐star copolymers with Y‐shaped arms and the presence of amorphous P(MEO₂MA‐co‐OEGMA) segments together led to the complete destruction of crystallinity of the PCL segments in the dendrimer‐star copolymer. In addition, the hydrophilicity–hydrophobicity transition of the dendrimer‐star copolymer film can be achieved by altering the external temperatures. The amphiphilic copolymers can self‐assemble into spherical nanomicelles in water. Because the lower critical solution temperature of the copolymers can be adjusted by varying the ratio of MEO₂MA and OEGMA, the tunable thermosensitive properties can be observed by transmittance, dynamic laser light scattering, and transmission electron microscopy (TEM). The release rate of model drug chlorambucil from the micelles can be effectively controlled by changing the external temperatures, which indicates that these unique high‐branched amphiphilic copolymers have the potential applications in biomedical field. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Controlled aggregation behavior of thermoresponsive polymeric micelles by introducing hydrophilic segments as corona components

Poly[N‐isopropylacrylamide‐co‐N‐(3‐methoxypropyl)acrylamide]‐b‐poly(D,L‐lactide) (P(IPAAm‐co‐MPAAm)‐b‐PLA) as a thermoresponsive block copolymer and PMPAAm‐b‐PLA as a nonthermoresponsive block copolymer were co‐assembled into thermoresponsive polymeric micelles in water. In addition, PMPAAm‐b‐P(IPAAm‐co‐MPAAm)‐b‐PLA triblock copolymer was assembled to form thermoresponsive micelles with a hydrophilic layer on the outermost surface of the thermoresponsive corona. Using both micelles, we investigated the effects of introducing hydrophilic polymer segments on micellar aggregation behavior at temperatures above the lower critical solution temperature (LCST) of the thermoresponsive micelles. Despite the external hydrophilic PMPAAm layer on PMPAAm‐b‐P(IPAAm‐co‐MPAAm)‐b‐PLA micelles, aggregation following dehydration of the thermoresponsive segments was not significantly suppressed at temperatures above the LCST due to the instability of the core‐corona state. In contrast, intermicellar aggregation was successfully controlled by blending P(IPAAm‐co‐MPAAm) and PMPAAm in the thermoresponsive corona region, even above the LCST. In particular, PMPAAm chains longer than the P(IPAAm‐co‐MPAAm) chains could regulate the hydrodynamic diameter of micellar aggregates at temperatures above the LCST. The micelles showed enhanced drug release rates in response to temperature changes above the LCST without precipitating from solution. These results indicated that a side‐by‐side structure of hydrophilic/thermoresponsive chains in the corona region could effectively control the micellar aggregation state after a thermal phase transition. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 1695–1704     

Amphiphilic block glycopolymers via atom transfer radical polymerization: Synthesis,self‐assembly and biomolecular recognition

In this work the synthesis of poly(butyl acrylate)‐b‐poly(2‐{[(D ‐glucosamin‐2‐N‐yl)carbonyl]oxy}ethyl methacrylate) (PBA‐b‐PHEMAGl) diblock glycopolymer and poly(2‐{[(D ‐glucosamin‐2‐N‐yl)carbonyl]oxy}ethyl methacrylate)‐b‐poly(butyl acrylate)‐b‐poly(2‐{[(D ‐glucosamin‐2‐N‐yl)carbonyl]oxy}ethyl methacrylate) (PHEMAGl‐b‐PBA‐b‐PHEMAGl) was performed via atom transfer radical polymerization. Monofunctional and difunctional poly(butyl acrylate) macroinitiators were used to synthesize the well‐defined diblock and triblock glycopolymers by chain extension reaction with the glycomonomer HEMAGl. The self‐assembly of these glycopolymers in aqueous solution was studied by dynamic light scattering and transmission electron microcopy, showing the coexistence of spherical micelles and polymeric vesicles. In addition, the biomolecular recognition capacity of these micelles and vesicles, containing glucose moieties in their coronas, was investigated using the lectin Concanavalin A, Canavalia Ensiformis, which specifically interacts with glucose groups. The binding capacity of Concanavalin A with glycopolymer is influenced by the copolymer composition, increasing with the length of HEMAGl glycopolymer segment in the block copolymer. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Synthesis and supramolecular self‐assembly of thermosensitive amphiphilic star copolymers based on a hyperbranched polyether core

A novel amphiphilic thermosensitive star copolymer with a hydrophobic hyperbranched poly (3‐ethyl‐3‐(hydroxymethyl)oxetane) (HBPO) core and many hydrophilic poly(2‐(dimethylamino) ethyl methacrylate) (PDMAEMA) arms was synthesized and used as the precursor for the aqueous solution self‐assembly. All the copolymers directly aggregated into core–shell unimolecular micelles (around 10 nm) and size‐controllable large multimolecular micelles (around 100 nm) in water at room temperature, according to pyrene probe fluorescence spectrometry and ¹H NMR, TEM, and DLS measurements. The star copolymers also underwent sharp, thermosensitive phase transitions at a lower critical solution temperature (LCST), which were proved to be originated from the secondary aggregation of the large micelles driven by increasing hydrophobic interaction due to the dehydration of PDMAEMA shells on heating. A quantitative variable temperature NMR analysis method was designed by using potassium hydrogen phthalate as an external standard and displayed great potential to evaluate the LCST transition at the molecular level. The drug loading and temperature‐dependent release properties of HBPO‐star‐PDMAEMA micelles were also investigated by using indomethacin as a model drug. The indomethacin‐loaded micelles displayed a rapid drug release at a temperature around LCST. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 668–681, 2008     

Finely Tuned Thermo‐Responsive Block Copolymer Micelles for Photothermal Effect‐Triggered Efficient Cellular Internalization

Although biodegradable amphiphilic block copolymer micelles have been widely applied in the clinical applications as drug delivery nanocarriers, low‐efficiency cellular internalization frequently reduces therapeutic efficacy of the loaded drugs. Here, photothermal effect‐promoted cellular internalization of finely tuned thermo‐responsive amphiphilic biodegradable block copolymer nanocarriers via noninvasive stimuli of near‐infrared (NIR) light irradiation is demonstrated. Amphiphilic block copolymers, poly(ε‐caprolactone)‐block‐poly(N‐isopropylacrylamide‐co‐N,N‐dimethylacrylamide) (PCL‐b‐P(NIPAM‐co‐DMA)), are prepared with finely tuned compositions of P(NIPAM‐co‐DMA) for desirable lower critical solution temperature of the block copolymer micelles in aqueous solution. The block copolymers are then used to co‐encapsulate doxorubicin and indocyanine green, which show high encapsulation efficiency and significant photothermal effect upon exposure to NIR light irradiation. The photothermal effect‐induced collapse and hydrophilic‐to‐hydrophobic transition of P(NIPAM‐co‐DMA) shells significantly enhance the interactions between drug‐loaded micelles and cell membranes, which dramatically promote the cellular internalization of the micelles and therapeutic efficacy of loaded anticancer drugs.