Oligo(ethylene Glycol) Monomethyl Ether Methacrylate Research Articles

Grafting Density Governs the Thermoresponsive Behavior of P(OEGMA-co-RMA) Statistical Copolymers.

Thermoresponsive copolymers that exhibit a lower critical solution temperature (LCST) have been exploited to prepare stimuli-responsive materials for a broad range of applications. It is well understood that the LCST of such copolymers can be controlled by tuning molecular weight or through copolymerization of two known thermoresponsive monomers. However, no general methodology has been established to relate polymer properties to their temperature response in solution. Herein, we sought to develop a predictive relationship between polymer hydrophobicity and cloud point temperature (TCP). A series of statistical copolymers were synthesized based on hydrophilic oligoethylene glycol monomethyl ether methacrylate (OEGMA) and hydrophobic alkyl methacrylate monomers and their hydrophobicity was compared using surface area-normalized partition coefficients (log Poct/SA). However, while some insight was gained by comparing TCP and hydrophobicity values, further statistical analysis on both experimental and literature data showed that the molar percentage of comonomer (i.e., grafting density) was the strongest influencer of TCP, regardless of the comonomer used. The lack of dependence of TCP on comonomer chemistry implies that a broad range of functional, thermoresponsive materials can be prepared based on OEGMA by simply tuning grafting density.

Triple Functional AB2 Unit-Modulated Facile Preparation of Bioreducible Hyperbranched Copolymers.

Facile preparation of hyperbranched polymers (HPs) has been advanced tremendously by the use of either various multifunctional agent-mediated controlled living radical polymerizations or a highly reactive ABx unit-modulated self-stepwise polymerizations. However, it remains, to our knowledge, a significant challenge to prepare HPs with simultaneously precisely controlled degree of branching (DB) and biorelevant signal-triggered degradation property for controlled release applications due to the respective limitations of the aforementioned two strategies. For this purpose, a triple functional AB2 unit, A-SS-B2 chain transfer agent (AB2 CTA), that integrates the merits of both multifunctional agents and highly reactive ABx units was designed and synthesized successfully to include a disulfide bond for reduction-triggered polymer degradation toward promoted intracellular release of encapsulated cargoes, a trithiocarbonate group for a universal reversible addition-fragmentation chain transfer (RAFT) polymerization of any vinyl-based monomer, and three terminal groups consisting of one azide and two alkyne functions for the generation of hyperbranched topology via a self-click coupling-based polymerization. A subsequent self-click polymerization of the resulting AB2 CTA by click coupling in the presence of CuSO4·5H2O and sodium ascorbate (NaVc) generated a hyperbranched polymer template (HPT) with precisely modulated DB and a plurality of CTA units for a universal reversible addition-fragmentation chain transfer (RAFT) polymerization of any vinyl-containing monomer. The HPT was next used as a multimacro-CTA for RAFT polymerization of a typical hydrophilic monomer, oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA), to demonstrate the potential of this HPT for a robust and facile production of bioreducible hyperbranched polymers for controlled release applications. The synthesized HPT-4-POEGMA can form unimolecular micelles with enhanced stability due to the hyperbranched structure, and the size of micelles varied in the range from 82.4 to 140.3 nm by a modulation of the molar feed ratio of monomer to HPT and polymerization time. More importantly, HPT-POEGMA micelles incubated with 10 mM glutathione (GSH) showed reduction-triggered cleavage of the disulfide links and polymer degradation for promoted intracellular doxorubicin (DOX) release and enhanced therapeutic efficiency. Taken together, this triple functional AB2 CTA provided a powerful means for the facile preparation of bioreducible hyperbranched polymers with precisely controlled DB for controlled release applications.

Fabrication of Acidic pH-Cleavable Polymer for Anticancer Drug Delivery Using a Dual Functional Monomer.

The preparation of tumor acidic pH-cleavable polymers generally requires tedious postpolymerization modifications, leading to batch-to-batch variation and scale-up complexity. To develop a facile and universal strategy, we reported in this study design and successful synthesis of a dual functional monomer, a-OEGMA that bridges a methacrylate structure and oligo(ethylene glycol) (OEG) units via an acidic pH-cleavable acetal link. Therefore, a-OEGMA integrates (i) the merits of commercially available oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA) monomer, i.e., hydrophilicity for extracellular stabilization of particulates and a polymerizable methacrylate for adopting controlled living radical polymerization (CLRP), and (ii) an acidic pH-cleavable acetal link for efficiently intracellular destabilization of polymeric carriers. To demonstrate the advantages of a-OEGMA ( Mn = 500 g/mol) relative to the commercially available OEGMA ( Mn = 300 g/mol) for drug delivery applications, we prepared both acidic pH-cleavable poly(ε-caprolactone)21- b-poly( a-OEGMA)11 (PCL21- b-P( a-OEGMA)11) and pH-insensitive analogues of PCL21- b-P(OEGMA)18 with an almost identical molecular weight (MW) of approximately 5.0 kDa for the hydrophilic blocks by a combination of ring-opening polymerization (ROP) of ε-CL and subsequent atom transfer radical polymerization (ATRP) of a-OEGMA or OEGMA. The pH-responsive micelles self-assembled from PCL21- b-P( a-OEGMA)11 showed sufficient salt stability, but efficient acidic pH-triggered aggregation that was confirmed by the DLS and TEM measurements as well as further characterizations of the products after degradation. In vitro drug release study revealed significantly promoted drug release at pH 5.0 relative to the release profile recorded at pH 7.4 due to the loss of colloidal stability and formation of micelle aggregates. The delivery efficacy evaluated by flow cytometry analyses and an in vitro cytotoxicity study in A549 cells further corroborated greater cellular uptake and cytotoxicity of Dox-loaded pH-sensitive micelles of PCL21- b-P( a-OEGMA)11 relative to the pH-insensitive analogues of PCL21- b-P(OEGMA)18. This study therefore presents a facile and robust means toward tumor acidic pH-responsive polymers as well as providesone solution to the trade-off between extracellular stability and intracellular high therapeutic efficacy of drug delivery systems using a novel monomer of a-OEGMA with dual functionalities.

Increasing the anticancer performance of bufalin (BUF) by introducing an endosome-escaping polymer and tumor-targeting peptide in the design of a polymeric prodrug.

A well-defined multifunctional brush-type polymeric prodrug covalently linked with an anticancer drug (bufalin, BUF), a tumor-targeting peptide (RGD), and an endosome-escaping polymer, poly(N,N-diethylaminoethyl methacrylate-co-butyl methacrylate (P(DEA-co-BMA)), was developed. Its anticancer performance against colon cancer was investigated in vitro and in vivo. Reversible addition-fragmentation transfer (RAFT) polymerization of oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA), 2-((3-(tert-butoxy)-3-oxopropyl)thio)ethyl methacrylate (BSTMA), and 2-(2-bromoisobutyryloxy)ethylmethacrylate (BIEM) afforded the multifunctional random copolymer, P(OEGMA-co-BSTMA-co-BIEM), in which hydrophilic POEGMA can stabilize nanoparticles in water, PBSTMA can be converted into carboxyl groups, and PBIEM can be employed as a macromolecular atom radical transfer polymerization (ATRP) initiator. The ATRP of DEA and BMA using P(OEGMA-co-BSTMA-co-BIEM) as a macromolecular ATRP initiator led to the formation of the pH-responsive brush-type copolymer, P(OEGMA-co-BSTMA)-g-P(DEA-co- BMA). After hydrolysis by trifluoroacetic acid and post-functionalization the final polymeric prodrug, P(OEGMA-co-BUF-co-RGD)-g-P(DEA-co-BMA), was obtained with a drug content of ∼7.8 wt%. P(OEGMA-co-BUF-co-RGD)-g-P(DEA-co-BMA) can be assembled into nanoparticles (BUF- NP-RGD) in aqueous solution with a diameter of 148.4 ± 0.7 nm and a zeta potential of -7.6 ± 0.4 mV. BUF-NP-RGD exhibited controlled drug release in the presence of esterase. Additionally, P(OEGMA-co- BSMA)-g-P(DEA-co-BMA) showed a significant hemolysis effect at a pH comparable to that of endosomes/lysosomes. Cell viability and a tumor-bearing nude mouse model were employed to evaluate the anticancer efficacy of BUF-NP-RGD. It was revealed that BUF-NP-RGD showed improved anticancer performance compared with that of free BUF both in vitro and in vivo. Histological and immunochemical analysis further demonstrated that BUF-NP-RGD exhibited improved cell apoptosis, angiogenesis inhibition, and an anti-proliferation effect.

Molecularly imprinted biocompatible magnetic nanoparticles for specific recognition of Ochratoxin A

In this paper, we synthesized highly selective oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA) based molecularly imprinted polymers for carcinogenic mycotoxin Ochratoxin A (OTA) on the surface of magnetic nanoparticles (MIP MNPs) via surface initiated atom transfer radical polymerization (SI-ATRP). Functional monomer OEGMA, crosslinker 1,2-ethyleneglycoldimethacrylate (EGDMA), template molecule OTA, initiator 3-bromopropyltrimethoxysilane (BPTS), Cu(I)Br and 2,2′-bipyridyl (2,2′-bpy) were selected for synthesis the MIP layer onto the surface of MNPs. After removing the template, the molecularly imprinted magnetic nanoparticles was used to detect OTA using UV–vis spectrophotometer. According to results, MIP MNPs showed fast adsorption, large adsorption capacity and highly selectivity toward to OTA. Also, the recovery of OTA in the spiked grape juice samples ranged from 97.1% to 97.4% with the relative standard deviation changed from 4.13% to 6.25%. As a result, MIP MNPs demonstrate high affinity to OTA targets have significant potential for clean-up applications in food samples

Photo-Triggered Release of Caged Camptothecin Prodrugs from Dually Responsive Shell Cross-Linked Micelles

We report on the fabrication of dynamic covalent shell cross-linked (SCL) micelles with hydrophobic cores conjugated with photocaged chemotherapeutic drugs and coronas functionalized with ligands for tumor cell targeting. Two types of amphiphilic diblock copolymers, P(CL-g-CPT)-b-P(OEGMA-co-MAEBA)-CPT and PCL-b-P(OEGMA-co-MAEBA-co-FA), were synthesized via the combination of ring-opening copolymerization (ROP) of e-caprolactone (CL) and 2-bromo-e-caprolactone (CL-Br), atom transfer radical polymerization (ATRP) of oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA) and p-(methacryloxyethoxy) benzaldehyde (MAEBA) comonomers, and “click” post-functionalization with photocaged camptothecin (CPT) prodrug and alkynyl-functionalized folic acid (FA) moieties, respectively. Mixed micelles coassembled from PCL-b-P(OEGMA-co-MAEBA-co-FA) and P(CL-g-CPT)-b-P(OEGMA-co-MAEBA)-CPT possess hydrophobic cores conjugated with photocaged CPT prodrugs and hydrophilic outer coronas covalently attached with aldehyde gr...

Thiol and pH dual-responsive dynamic covalent shell cross-linked micelles for triggered release of chemotherapeutic drugs

We report on the fabrication of dynamic covalent shell cross-linked (SCL) micelles of amphiphilic diblock copolymers functionalized with aldehyde moieties in the hydrophilic block by utilizing difunctional crosslinkers cleavable in response to pH and thiols. Well-defined amphiphilic diblock copolymer, PCL-b-P(OEGMA-co-MAEBA), was synthesized via ring opening polymerization (ROP) of ε-caprolactone (CL) and atom transfer radical polymerization (ATRP) of oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA) and p-(methacryloxyethoxy)benzaldehyde (MAEBA) comonomers. In aqueous solution, the diblock copolymer self-assembles into micelles consisting of hydrophobic PCL cores and hydrophilic P(OEGMA-co-MAEBA) coronas covalently anchored with aldehyde groups. The subsequent shell cross-linking reaction was conducted at pH 6.2 upon addition of difunctional dithiolbis(propanoic dihydrazide) (DTP). The formation of dynamic acylhydrazone cross-linking linkages was facilitated under the catalysis of aniline. The obtained SCL micelles can be de-crosslinked via two biologically relevant modes, namely, acidic pH-triggered cleavage of acylhydrazone bonds into aldehyde and hydrazide and thiol-triggered cleavage of disulfide linkages, which have been utilized for triggered release of physically encapsulated chemotherapeutic drugs. The dual-responsive dynamic covalent SCL micelles were examined by dynamic laser light scattering (LLS), 1H NMR, Ellman's assay, and enzymatic degradation tests. In addition, camptothecin (CPT)-loaded SCL micelles were used to investigate thiol and pH-modulated CPT release profiles. Compared with CPT-loaded non-cross-linked (NCL) micelles, CPT-loaded SCL micelles can largely minimize drug leakage under physiological conditions, whilst exhibiting accelerated drug release under mildly acidic or thiol-rich microenvironments, which are relevant to those of acidic organelles (endosomes and lysosomes) or cytosol within tumor cells. Cell cytotoxicity studies revealed that drug-free SCL micelles are almost nontoxic, whereas CPT-loaded SCL micelles can efficiently deliver chemotherapeutic drug (CPT) into HepG2 cells, leading to considerable nucleic accumulation at extended incubation duration. The reported dynamic covalent shell cross-linking strategy can exert intricate control concerning the micellar stability and the release profile of encapsulated drugs in response to biological microenvironments, which augurs well for their potential use as novel smart nanocarriers for drug delivery in cancer chemotherapy.

Optimization of brush-like cationic copolymers for nonviral gene delivery.

Polyethylenimine (PEI) is one of the most broadly used polycations for gene delivery due to its high transfection efficiency and commercial availability but materials are cytotoxic and often polydisperse. The goal of current work is to develop an alternative family of polycations based on controlled living radical polymerization (CLRP) and to optimize the polymer structure for efficient gene delivery. In this study, well-defined poly(glycidyl methacrylate)(P(GMA)) homopolymers were synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization followed by decoration using three different types of oligoamines, i.e., tetraethylenepentamine (TEPA), pentaethylenehexamine (PEHA), and tris(2-aminoethyl)amine (TREN), respectively, to generate various P(GMA-oligoamine) homopolycations. The effect of P(GMA) backbone length and structure of oligoamine on gene transfer efficiency was then determined. The optimal polymer, P(GMA-TEPA)(50), provided comparable transfection efficiency but lower cytotoxicity than PEI. P(GMA-TEPA)(50) was then used as the cationic block in diblock copolymers containing hydrophilic N-(2-hydroxypropyl) methacrylamide (HPMA) and oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA). Polyplexes of block copolymers were stable against aggregation in physiological salt condition and in Opti-MEM due to the shielding effect of P(HPMA) and P(OEGMA). However, the presence of the HPMA/OEGMA block significantly decreased the transfection efficacy of P(GMA-TEPA)(50) homopolycation. To compensate for reduced cell uptake caused by the hydrophilic shell of polyplex, the integrin-binding peptide, RGD, was conjugated to the hydrophilic chain end of P(OEGMA)(15)-b-P(GMA-TEPA)(50) copolymer by Michael-type addition reaction. At low polymer to DNA ratios, the RGD-functionalized polymer showed increased gene delivery efficiency to HeLa cells compared to analogous polymers lacking RGD.

Photo‐Degradable, Protein–Polyelectrolyte Complex‐Coated, Mesoporous Silica Nanoparticles for Controlled Co‐Release of Protein and Model Drugs

The fabrication of photo-degradable, protein-polyelectrolyte complex (PPC)-coated, mesoporous silica nanoparticles (MSNs) and their controlled co-release of protein and model drugs is reported. Random copolymers composed of oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA), and a photolabile o-nitrobenzyl-containing monomer, 5-(2'-(dimethylamino)ethoxy)-2-nitrobenzyl methacrylate (DENBMA), are first anchored onto the MSNs and then quaternary aminated, to obtain positively charged P(OEGMA-co-TENBMA) which exhibits photo-induced charge conversion characteristics. PPCs consisting of P(OEGMA-co-TENBMA) and the protein bovine serum albumin (BSA) are utilized as capping agents for the nanopores of the MSNs. Upon UV irradiation, charge conversion of P(OEGMA-co-TENBMA) can lead to the disruption of PPCs on MSNs and co-release of BSA and rhodamine B by electrostatic repulsion.

Molecular Sieving on the Surface of a Protein Provides Protection Without Loss of Activity

AbstractTethering polymers to surfaces represents the cornerstone of a wide range of applications, including the stabilization of colloids/biomolecules and the preparation of functional coatings. Unfortunately, despite the prevalence of protein‐tethered polymers in the pharmaceutical sector, the analysis of such polymer monolayers on a molecular level is difficult. In this work, simple 1H NMR spectroscopy and the catalytic properties of α‐chymotrypsin are used to analyze the conformational/permeability properties of protein‐bound monolayers of poly(oligoethyleneglycol monomethylether methacrylate) (pOEGMA), a biocompatible comb‐polymer of interest in the biomedical field. By analyzing >100 distinct conjugates of α‐chymotrypsin and pOEGMA, a detailed picture of the behavior of pOEGMA on the surface of a protein was obtained. Remarkably, control of polymer conformation and inter‐penetration produced a thus far overlooked molecular sieving effect. The application of this effect for the “smart” PEGylation of proteins is portrayed, from which insight is provided for the design of other therapeutic bioconjugates and functional coatings with selective permeability properties.

AGET ATRP of oligo(ethylene glycol) monomethyl ether methacrylate in inverse microemulsion

A water soluble monomer, oligo(ethylene glycol) monomethyl ether methacrylate (OEOMA), was successfully polymerized in an inverse microemulsion system via the activator generated by electron transfer atom transfer radical polymerization (AGET ATRP) technique. Stable colloidal particles with a readily tunable size, ranging from ca. 35 to 200 nm, were obtained by adjusting the amount and the type of reducing agent used for the generation of activators in the AGET ATRP and by adjusting the aqueous phase fraction in the inverse microemulsion system. The formed particles contained well-defined water-soluble polymers with relatively narrow molecular weight distribution (Mw/Mn < 1.5). The introduction of a small amount of divinyl cross-linkers into the system allowed the synthesis of cross-linked hydrogel nanoparticles. The cross-linked particles retained their morphology when they were redispersed in methanol or water, as evidenced by the constant particle size determined by dynamic light scattering (DLS).

Amphiphilic multiarm star block copolymer-based multifunctional unimolecular micelles for cancer targeted drug delivery and MR imaging

We report on the fabrication of multifunctional polymeric unimolecular micelles as an integrated platform for cancer targeted drug delivery and magnetic resonance imaging (MRI) contrast enhancement under in vitro and in vivo conditions. Starting from a fractionated fourth-generation hyperbranched polyester (Boltorn H40), the ring-opening polymerization of ɛ-caprolactone (CL) from the periphery of H40 and subsequent terminal group esterification with 2-bromoisobutyryl bromide afforded star copolymer-based atom transfer radical polymerization (ATRP) macroinitiator, H40-PCL-Br. Well-defined multiarm star block copolymers, H40-PCL-b-P(OEGMA-co-AzPMA), were then synthesized by the ATRP of oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA) and 3-azidopropyl methacrylate (AzPMA). This was followed by the click reaction of H40-PCL-b-P(OEGMA-co-AzPMA) with alkynyl-functionalized cancer cell-targeting moieties, alkynyl-folate, and T1-type MRI contrast agents, alkynyl-DOTA–Gd (DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakisacetic acid), affording H40-PCL-b-P(OEGMA-Gd-FA). In aqueous solution, the amphiphilic multiarm star block copolymer exists as structurally stable unimolecular micelles possessing a hyperbranched polyester core, a hydrophobic PCL inner layer, and a hydrophilic P(OEGMA-Gd-FA) outer corona. H40-PCL-b-P(OEGMA-Gd-FA) unimolecular micelles are capable of encapsulating paclitaxel, a well-known hydrophobic anticancer drug, with a loading content of 6.67 w/w% and exhibiting controlled release of up to 80% loaded drug over a time period of ∼120 h. In vitro MRI experiments demonstrated considerably enhanced T1 relaxivity (18.14 s−1 mm−1) for unimolecular micelles compared to 3.12 s−1 mm−1 for that of the small molecule counterpart, alkynyl-DOTA–Gd. Further experiments of in vivo MR imaging in rats revealed good accumulation of unimolecular micelles within rat liver and kidney, prominent positive contrast enhancement, and relatively long duration of blood circulation. The reported unimolecular micelles-based structurally stable nanocarriers synergistically integrated with cancer targeted drug delivery and controlled release and MR imaging functions augur well for their potential applications as theranostic systems.

Responsive Polymers-Based Dual Fluorescent Chemosensors for Zn2+Ions and Temperatures Working in Purely Aqueous Media

We report on the fabrication of responsive double hydrophilic block copolymers (DHBCs)-based dual fluorescent chemosensors for Zn(2+) ions and temperatures and investigate the effects of thermo-induced micellization and detection conditions on the probing sensitivity and binding reversibility of Zn(2+) ions. A novel quinoline-based polarity-sensitive and Zn(2+)-recognizing fluorescent monomer (ZQMA, 6) was synthesized at first. Well-defined DHBCs bearing quinoline-based Zn(2+)-recognizing moieties (ZQMA) in the thermoresponsive block, PEG-b-P(MEO(2)MA-co-OEGMA-co-ZQMA), were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-(2-methoxyethoxy)ethyl methacrylate (MEO(2)MA), oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA), and ZQMA in the presence of PEG-based macroRAFT agent. The OEGMA contents in the thermoresponsive block varied in the range of 0-12.0 mol % to tune their lower critical solution temperatures (LCSTs). At 20 °C, almost nonfluorescent PEG-b-P(MEO(2)MA-co-ZQMA) molecularly dissolved in water and can selectively bind with Zn(2+) ions over other common metal ions, leading to prominent fluorescence enhancement due to the coordination of ZQMA with Zn(2+). At a polymer concentration of 0.2 g/L, the Zn(2+) detection limit can be down to ~3.0 nM. PEG-b-P(MEO(2)MA-co-ZQMA) self-assembles into micelles possessing P(MEO(2)MA-co-ZQMA) cores and well-solvated PEG coronas upon heating to above the LCST, and the fluorescence intensity exhibit ~6.0-fold increase due to the fact that ZQMA moieties are now located in a more hydrophobic microenvironment. Compared to the unimer state at 20 °C, although PEG-b-P(MEO(2)MA-co-ZQMA) micelles possess a slightly decreased detection limit for Zn(2+) (~14 nM), reversible binding between ZQMA moieties and Zn(2+) ions at 37 °C can be achieved, as evidenced by the on/off switching of fluorescence emission via the sequential addition of Zn(2+) and EDTA. In vitro fluorescence imaging studies suggested that the micelles can effectively enter into living cells and sensitively respond to Zn(2+) ions. This work represents the first example of a purely aqueous-based polymeric Zn(2+) sensing system by integrating the well-developed small molecule Zn(2+)-sensing moieties with stimuli-responsive DHBCs.

Fluorescent water-soluble responsive polymers site-specifically labeled with FRET dyes possessing pH- and thermo-modulated multicolor fluorescence emissions as dual ratiometric probes

We reported on the synthesis of well-defined thermoresponsive polymers labeled with fluorescence resonance energy transfer (FRET) pairs at chain middle and terminals, which can act as single chain-based dual ratiometric fluorescent probes for pH and temperature under extremely dilute conditions. Starting from difunctional initiator containing a 7-nitro-2,1,3-benzoxadiazole (NBD) moiety, the atom transfer radical polymerization (ATRP) of oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA) and di(ethylene glycol) monomethyl ether methacrylate (DEGMA), and the subsequent terminal group functionalization with Rhodamine B (RhB)-ethylenediamine derivative afforded thermoresponsive NBD-P(OEGMA-co-DEGMA)-RhB2, which were labeled with FRET donor (NBD) and acceptor moieties (RhB) at the chain middle and terminals. The fluorescence emission of terminal RhB functionalities is highly pH-dependent, i.e, non-fluorescent in neutral or alkaline media (spirolactam form) and highly fluorescent in acidic media (ring-opened acyclic form), thus the off/on switching of FRET process can be facilely modulated by solution pH. Moreover, at acidic pH and highly dilute conditions, the thermo-induced chain collapse and extension of NBD-P(OEGMA-co-DEGMA)-RhB2 can effectively modulate the spatial distance between FRET donor and acceptor moieties, leading to prominent changes in FRET efficiencies. The site-specific incorporation of one FRET donor and two pH-switchable acceptors at the chain middle and terminals of thermoresponsive polymers allows for the effective off/on switching and the modulation of efficiency of FRET processes by dually playing with solution pH and temperatures. This work represents the first report of single thermoresponsive polymer chains acting as dual ratiometric fluorescent probes under highly dilute conditions.

Fluorescent pH-Sensing Organic/Inorganic Hybrid Mesoporous Silica Nanoparticles with Tunable Redox-Responsive Release Capability

We report on the fabrication of fluorescent pH-sensing organic/inorganic hybrid mesoporous silica nanoparticles (MSN) capable of tunable redox-responsive release of embedded guest molecules. The reversible addition-fragmentation chain transfer (RAFT) copolymerization of N-(acryloxy)succinimide (NAS), oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA), and 1,8-naphthalimide-based pH-sensing monomer (NaphMA) at the surface of MSN led to fluorescent organic/inorganic hybrid MSN. The obtained hybrid MSN exhibits excellent water dispersibility and acts as sensitive fluorescent pH probes in the range pH 4-8 due to the presence of NaphMA moieties. After loading with rhodamine B (RhB) as a model drug molecule, P(NAS-co-OEGMA-co- NaphMA) brushes at the surface of hybrid MSN were cross-linked with cystamine to block nanopore entrances for the effective retention of guest molecules. Taking advantage of disulfide-containing cross-linkers, the release rate of RhB can be easily adjusted by adding varying concentrations of dithiothreitol (DTT), which can cleave the disulfide linkage to open blocked nanopores. The increase of DTT concentration from 0 to 20 mM led to 20-30 times enhancement of RhB release rate. The reported multifunctional hybrid MSN augurs well for applications in controlled-release nanocarriers, cell and tissue imaging, and clinical diagnosis.

AGET ATRP in water and inverse miniemulsion: A facile route for preparation of high‐molecular‐weight biocompatible brush‐like polymers

AbstractActivators generated by electron transfer for atom transfer radical polymerization (AGET ATRP) of oligo(ethylene glycol) monomethyl ether methacrylate (OEOMA) was investigated in homogeneous aqueous solution targeting DP = 1000, and in inverse miniemulsion targeting DP = 600, at 30 °C. Several reaction parameters were examined in the preparation of biocompatible, brush‐like, high‐molecular‐weight, water‐soluble polymers. They include concentration of ascorbic acid (AscA), ratio of water to OEOMA, mode of addition of AscA, and ratio of initiator to Cu(II) complex. The results obtained in these studies indicate that AGET ATRP retains all of the benefits of normal ATRP and, additionally, provides a facile route for the preparation of well‐controlled high‐molecular‐weight polymers because of the use of oxidatively stable catalyst precursors. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1771–1781, 2009