Polymer Vesicles with Upper Critical Solution Temperature for Near-infrared Light-triggered Transdermal Delivery of Metformin in Diabetic Rats

Near-infrared light(NIR)triggered transdermal drug delivery systems are of great interest due to their on-demand drug release,which enable to enhance drug treatment efficiency as well as reduce side effect.Herein,a NIR-triggered microneedle(MN)patch array has been fabricated through depositing the photothermal conversion agent and anti-diabetic drug-loaded polymer vesicles with upper critical solution temperature(UCST)into dissolvable polymer matrix.The UCST-type polymer has a clearing point temperature of 41℃ and the drug-loaded polymer vesicles present excellent NIR-triggered and temperature responsive drug release behavior in vitro due to the disassociation of polymer vesicles upon NIR irradiation.After applying MNs to diabetic rats,significant hypoglycemic effect is achieved upon interval NIR irradiation and the blood glucose concentration can decrease to normal state for several hours,which enables to achieve the goal of on-demand drug release.This work suggests that the NIR-triggered MN drug release device has a potential application in the treatment of diabetes,especially for those requiring an active drug release manner.

Visualizing phase transition of upper critical solution temperature (UCST) polymers with AIE

The stimuli-responsive polymers with upper critical solution temperatures(UCST) are highly attractive for drug delivery applications. However, the phase transition process of UCST polymer is usually characterized by turbidity measurement and electron microscopy, which are significantly restricted by low sensitivity and static observation. In contrary, the fluorescence technique has significant advantages in terms of high sensitivity, easy operation, and dynamic observation. However, the conventional fluorophores suffer from the drawbacks of aggregation-caused quenching(ACQ) after being encapsulated by UCST polymers, which are not suitable for direct visualization of the phase transition process. To tackle this challenge, we herein developed a series of UCST polymers based on polyacrylamides decorated with bile acid and aggregation-induced emission(AIE)-active tetraphenylethene(TPE) groups, which can be used for direct fluorescence monitoring of the phase transition process. Moreover, the AIE-active UCST polymers can serve as drug carriers, which can not only monitor the drug release process under thermal stimuli, but also verify the drug release by fluorescence recovery after thermal stimuli. It is expected that the AIE-active UCST polymers with self-monitoring ability are promising for biomedical applications.

Supramolecular control over thermo-responsive systems with lower critical solution temperature behavior

Lower critical solution temperature(LCST)is the critical temperature below which the solution is miscible for all compositions and above which the solution becomes a suspension.The study of LCST properties has become a central research topic due to its profound impact on the applications of stimuli-responsive materials.Inspired by the marriage between materials science and supramolecular chemistry,the introduction of supramolecular pairs and interactions into polymeric LCST systems is increasingly practiced.Especially,supramolecular interactions provide precise control over LCST behavior in both water and organic solvents.Furthermore,supramolecular interactions not only control or adjust LCST behavior(supramolecular interaction controlled LCST),but also induce LCST phase behavior in species lack of thermo-sensitive properties(supramolecular interaction induced LCST).In this review,we summarize the applications of supramolecular interactions in LCST systems.By examining the relationship between supramolecular interactions and LCST changes,we further discuss the differences between supramolecular interaction controlled LCST and supramolecular interaction induced LCST.We hope this review will give our readers a snapshot on how the supramolecular interactions influence the LCST behavior in various systems,and benefit them with different applications.

INFINITELY MANY SOLUTIONS FOR A NONLINEAR ELLIPTIC EQUATION INVOLVING CRITICAL SOBOLEV EXPONENT

In this paper, it is proved that the following boundary value problem [GRAPHICS] admits infinitely many solution for 0 < lambda < lambda-1, n greater-than-or-equal-to 5 and for ball regions OMEGA = B(R)(0).

The Influence of Ce(NO_3)_3·6H_2O on the Inhibitive Effect of Ca(NO_2)_2 in Simulated Concrete Pore Solution

The effects of cerium nitrite on corrosion behaviors of carbon steel in simulated concrete pore solutions were studied with the methods of linear polarization, electrochemical impedance spectroscopy and surface analysis. In pore solutions in the presence of Ce（NO3）3？6H2O, the corrosion potential, polarization resistance and impedance of carbon steel obviously increased in contrast to the situation in the absence of cerium salts. The pore solution with [NO2-] / [Cl-] = 0.3 and 0.1% Ce（NO3）3？6H2O, carbon steel shows better corrosion resistance than that in the pore solution with [NO2-] / [Cl-] = 0.6, which indicates that a small amount of Ce（NO3）3？6H2O in pore solutions can effectively promote passivation of the steel and reduce the threshold [NO2-] / [Cl-] ratio for corrosion control. The surface layer formed in cerium salt containing pore solutions is more compact and smooth and 1.36%Ce is examined on the sample surface. The addition of 0.1% Ce（NO3）3？6H2O in pore solutions can decrease the corrosion rate of steel in pore solutions and has little influence on pH change of the solutions. However, more cerium nitrate addition above 0.1% may result in pH decrease of the solution.

Salt Effect on the Phase Transition Behavior of Thermo-sensitive Polyamide

Phase transition behavior and influence of ions on the thermo-sensitive polyamide with polyethylene glycol as the main chain were studied in detail. By measuring the light transmission rates of polymer solutions, the change of its lower critical solution temperature （LCST） in the salt solution was investigated. It was found that a reversible phase transition of the polyamide occurred at the LCST and finished in a narrow temperature range. The LCST was associated with species of ions in salt solution. Anions had a great impact on the phase transition performance of the thermo-sensitive polyamide, while the cations had a slight influence on the phase transition. Different anions had different coagulation ability to ‘salt-out＇ the polyamide. The order was： CO2-3〉SiO2-3〉HPO2-4〉OH-〉Cl-〉HCO3-〉HSOa-〉NO2-〉NO3-.

Synthesis and Properties of Poly (N-isopropylacrylamide) and Poly (N-isopropylacrylamide-co-acrylamide) Hydrogels

The thermosensitive poly （ N-isopropylacrylamide ） （PNIPAAm） and poly （N-isopropylacrylamide-co-acrylamide） [ poly （NIPAAm-co-AAm） ] hydrogels with different acrylamide molar percentage are prepared by radiation polymerization using Co^60 γ-ray. Their swelling equilibrium data in the media of deionized water, NaCl aqueous solutions and different pH buffer solutions are determined. It appears that lower critical solution temperature （LCST） of the hydrogels will drop with the increase of ionic strength and increase with the rising of acrylamide content, A semi-empirical formula is set up with the experimental results. Moreover, it also indicates that this copolymer is pH-sensitive, which is similar to the homopolymer of PNIPAAm.

The Existence of a Weak Solution of Inhomogeneous Quasilinear Elliptic Equation with Critical Growth Conditions

In this paper, we get the existence of a weak solution of the following inhomogeneous quasilinear elliptic equation with critical growth conditions: where N≥2, f（x,u）～|u|m-1eb|u|γat +∞, with γ=N/N-1, m≥1, b】0.

pH-sensitive tunable thermochromic hydrogel with carbon quantum dots for smart windows

Thermoresponsive hydrogels have been designed for smart windows to dynamically modulate solar radiation,but their inherent drawbacks of long response time and imperfectly matched phase transition temperature have limited their wide applications.This work reports a novel composite hydrogel consisting of hydroxypropyl cellulose,polyacrylic acid,and carbon quantum dots with intriguing features of tunable transition temperature and enhanced switching speed.The composite hydrogel demonstrated flexible tunability in transition temperature by controlling the hydrogen ion concentration and a fast response speed by dopping with carbon dots for efficient photothermal conversion.The building energy simulation was carried out to investigate the impacts of transition temperature variations and solar regulations on the space cooling/heating loads under different climate conditions,revealing the necessity of tunability of both transition temperature and solar transmittance in thermochromic smart windows.This novel design of thermochromic composite hydrogel provides insight into theoretical and experimental support for future adaptive building envelopes.

Large number of bubble solutions for the equation ?u + K(y)u^((N+2)/(N- 2)± ε)= 0 on R^N

This paper concerns the following nonlinear elliptic equation:{?u + K(y)u^((N+2)/(N-2)±ε)= 0, u > 0, y ∈ R^N,u ∈ D^(1,2)(R^N),where ε > 0, N≥5, K(y) is positive and radially symmetric. We show that, under some local conditions on K(y), this problem has large number of bubble solutions if ε is small enough. Moreover, for each m ∈ [2, N- 2),there exists solutions whose functional energy is in the order of ε^(-(N-2-m)/((N-2)~2)).

Multiple Solutions for a Quasilinear Second Order Differential Equation Depending on a Parameter

The purpose of this paper is to use a very recent three critical points theorem due to Bonanno and Marano to establish the existence of at least three solutions for the quasilinear second order differential equation on a compact interval[a,b] R{-u＇＇=（λf（x,u）＋g（u））h（u＇）,in（a,b）,u（a）=u（b）=0under ppropriate hypotheses.We exhibit the existence of at least three（weak）solutions and,and the results are illustrated by examples.

Temperature/pH dual-responsive reversible morphology evolution of block copolymer microparticles under three-dimensional confinement

Development of block copolymer(BCP)microparticles with switchable morphology in response to external stimuli is important for exploiting new intelligent materials.In this work,thermo/p H dual-responsive nanoparticles(NPs)were employed as a cosurfactant to modulate the self-assembly morphology of polystyrene-b-poly(2-vinylpyridine)(PS-b-P2VP)microparticles within confined emulsion droplets.The co-surfactant was synthesized by grafting poly(acrylic acid)-b-poly(N-isopropylacrylamide)onto the surface of Fe3O4NP.The introduction of the dual-responsive co-surfactant enabled thermo/p H dual-responsive reversible morphology transition of the PS-b-P2VP microparticles by tailoring the hydrophobicity and interfacial affinity of the cosurfactant.By using this strategy,the thermo-inert PS-b-P2VP self-assembled into pupa-like microparticles at T=10℃ and p H7.5,which could transform into tulip-like microparticles when T was increased to 50℃.When the p H value was increased to 11,the pupa-like particles turned into onion-like microparticles although the PS-b-P2VP was inert to alkali.However,the pupa-like microparticles remained unchanged when both T and p H were simultaneously increased.The PAA-b-PNIPAM-grafted Fe3O4NP surfactants showed obvious advantages over the linear PAA-b-PNIPAM surfactants in modulating the morphology transition,since the linear PAA-b-PNIPAM could not induce the reversible shape transition of microparticles.Our work provides an efficient strategy to achieve reversible shape transformation of BCP microparticles while the internal phase structure is preserved,which may be utilized to switch the structural color properties of BCP microparticles.

Synthesis of a Kind of Temperature-responsive Cell Culture Surface for Corneal Sheet

In this study, acrylic acid （AA） and 4-azidoaniline were used to modify poly （N-isopropylacrylamide） （NIPAAm） in order to fabricate temperature-responsive surface for corneal epithelia cell adhesion and detachment. First, NIPAAm was copolymerized with acrylic acid. Then, the copolymer was coupled with azidoaniline to synthesize AzPhPIA, derivative of p（NIPAAm-co-AA）, which possesses both thermo- and photo-sensitivities. Second, the synthesized copolymer was characterized by high performance liquid chromatography （HPLC）, Fourier transform infrared （FTIR） and a CHN analyzer. The thermo-sensitivity was characterized by temperature reducing experiment, contact angle measurement and low critical solution temperature （LCST） testing. Third, the derivatized copolymer was immobilized by photolithography on a polystyrene plate, and then the surface characterization of AzPhPIA-coated polystyrene plate （PSt） was measured by electron spectroscopy for chemical analysis （ESCA）. The thermo-sensitivity and cytocompatibility of the AzPhPIA-coated PSt were investigated by corneal epithelial cells culture. The results revealed that the AzPhPIA-coated PSt exhibited good cytocompatibility and cell detachability when temperature decreased.

Tunable LCST-type phase behavior of [FeCl4]--based ionic liquids in water

In this work, 16 kinds of [FeCl4]--based magnetic ionic liquids （ILs） with different cation structures have been designed and synthesized, and their structures are characterized by IR and Raman spectroscopy. Then the lower critical solution temperature （LCST）-type phase behavior of these magnetic ILs in water is investigated as a function of concentration. It is shown that cat- ion structure, alkyl chain length and molar ratio of FeCl3/chloride IL have a significant influence on the LCST of the mixtures. The phase separation temperature can be tuned efficiently by these factors. Meanwhile, the LCST-type phase separation pro- cess is also investigated by dynamic light scattering. The results support the mechanism that the hydrogen bonds of the [Fefl4]- anion with water have been gradually disrupted to form ILs aggregates with increasing temperature. In addition, the stability of the ILs in water is also examined in some details. These LCST-type phase separation systems may have potential applications in extraction and separation techniques at room temperature.

Controlling the gelation temperature of biomimetic polyisocyanides

Thermosensitive polymers show an entropy-driven transition from a well-solvated to a poorly solvated polymer chain, resulting in a more compact globular conformation. The transition at the lower critical solution temperature（LCST） is often sharp, which allows for a wide range of smart material applications.At the LCST, oligo（ethylene glycol）-substituted polyisocyanides（PICs） form soft hydrogels, composed of polymer bundles similar to biological gels, such as actin, fibrin and intermediate filaments. Here, we show that the LCST of PICs strongly depends linearly on the length of the ethylene glycol（EG） tails; every EG group increases the LCSTand thus the gelation temperature by nearly 30 ℃. Using a copolymerisation approach, we demonstrate that we can precisely tailor the gelation temperature between 10 ℃ and 60 ℃and, consequently, tune the mechanical properties of the PIC gels.

Micromechanical properties of poly(N-isopropylacrylamide)hydrogel microspheres determined using a simple method

Temperature-responsive poly（N-isopropylacrylamide） （PNIPAM） hydrogel microspheres have attracted extensive attention because of their promising diverse biomedical applications. A quantitative understanding of the micromechanical properties of these microspheres is essential for their practical application. Here, we report a simple method for the characterization of the elastic properties of PNIPAM hydrogel microspheres. The results show that PNIPAM hydrogel microspheres exhibit elastic deformation and the obtained force-deformation experimental data fits the Hertz theory well. The moduli of elasticity of the PNIPAM hydrogel microspheres prepared under different conditions were systematically investigated in this work for the first time. The PN1PAM hydrogel microsphere composition significantly affects their micromechanical properties and their temperature sensitivity behavior. PNIPAM hydrogel microspheres with a larger equilibrium volume change have a lower modulus of elasticity. The modulus of elasticity of the PNIPAM hydrogel microspheres at body temperature （37 ℃, above the lower critical solution temperature （LCST） of PNIPAM） is much higher than that at room temperature （25 ℃, below the LCST of PNIPAM） because ofthermo-induced volume shrinkage and an increase in stiffness. These results provide valuable guidance for the design of smart materials for practical biomedical applications. Moreover, the simple microcompression method presented here also provides a versatile way to investigate the micromechanical properties of microscopic biomedical materials.

Supramolecular control over LCST behavior of hybrid macrocyclic system based on pillar[5]arene and crown ether

A hybrid system containing a pillar[5]arene unit and ten crown ether moieties was developed.The LCST behavior and thermo-responsive ness were successfully introduced into this pillar[5]arene-crown ether system.Both host-guest interactions and salting-out effect displayed great effects in realizing the supramolecular control over LCST properties and the rmo-re sponsiveness.Compa red with the individual macrocycles,this hybrid macrocycle system dramatically amplified the supramolecular control effect over LCST behavior.

Multifunctional Gd-CuS loaded UCST polymeric micelles for MR/PA imaging-guided chemo-photothermal tumor treatment

Hepatocellular carcinoma(HCC)is a life-threatening disease for which there is no effective treatment currently.Novel theranostics simultaneously having excellent imaging and therapeutic functions are highly desired in cancer therapy.Herein,we develop the sialic acid(SA)modified polymeric micelles at an upper critical solution temperature(UCST)of 43℃(sialic acid-poly(ethylene glycol)-poly(acrylamide-co-acrylonitrile),SA-PEG-p(AAm-co-AN)),which further encapsulated with doxorubicin(DOX)and Gd-CuS nanoparticles(Gd-CuS NPs)for chemo-photothermal treatment of HCC guided by magnetic resonance(MR)/photoacoustic(PA)dual-mode imaging.The resultant SA-PEG-p(AAm-co-AN)/DOX/Gd-CuS(SPDG)had an excellent photothermal conversion efficiency,enabling SPDG with an instantaneous release behavior of DOX under near-infrared(NIR)irradiation.This study also revealed that SPDG could actively target to HCC,which was due to that SA had a high affinity with E-selectin overexpressed at the tumor site.Moreover,benefiting from the HCC-targeted ability and NIR light-controlled on-demand delivery of DOX,SPDG showed a superior potential in MR/PA dual-mode imaging-guided chemo-photothermal treatment.Overall,our study reveals that the designed SPDG may be used as an ideal multifunctional nanoplatform for cancer theranostics.

Immunogenic-cell-killing and immunosuppression-inhibiting nanomedicine

Combining chemo-therapeutics with immune checkpoint inhibitors facilitates killing cancer cells and activating the immune system through inhibiting immune escape.However,their treatment effects remain limited due to the compromised accumulation of both drugs and inhibitors in certain tumor tissues.Herein,a new poly(acrylamide-co-acrylonitrile-co-vinylimidazole-co-bis(2-methacryloyl)oxyethyl disulfide)(PAAVB)polymer-based intelligent platform with controllable upper critical solution temperature(UCST)was used for the simultaneous delivery of paclitaxel(PTX)and curcumin(CUR).Additionally,a hyaluronic acid(HA)layer was coated on the surface of PAAVB NPs to target the CD44-overexpressed tumor cells.The proposed nanomedicine demonstrated a gratifying accumulation in tumor tissue and uptake by cancer cells.Then,the acidic microenvironment and high level of glutathione(GSH)in cancer cells could spontaneously decrease the UCST of polymer,leading to the disassembly of the NPs and rapid drug release at body temperature without extra-stimuli.Significantly,the released PTX and CUR could induce the immunogenic cell death(ICD)to promote adaptive anti-tumor immunogenicity and inhibit immunosuppression through suppressing the activity of indoleamine 2,3-dioxygenase 1(IDO1)enzyme respectively.Therefore,the synergism of this intelligent nanomedicine can suppress primary breast tumor growth and inhibit their lung metastasis.