Polymeric Hydrogel Nanocapsules: A Thermo and pH Dual-responsive Carrier for Sustained Drug Release

Hydrogel capsules show attractive prospects in drug delivery recently because of high drug loading and sustained release behavior. In this study we reported a simple and convenient route to fabricate poly(acrylic acid)-poly(N-isopropylacrylamide)(PAA-PNIPAm) hydrogel capsules by using hydroxypropylcellulose-poly(acrylic acid)(HPC-PAA) complexes as the templates. The capsules showed a high drug loading(～280% to the weight of capsules) for Doxorubicin hydrochloride. The release of drug from the capsules was responsive to the temperature and p H of the surroundings, showing a low-rate but sustained release behavior favorable for low-toxic and long-term therapy. Together with the convenient preparation, high drug loading, dual responsivity as well as the sustained release feature, it is implied that this polymeric hydrogel capsule might be a promising candidate for new drug carriers.

SIX SIGMA OPTIMIZATION IN SHEET METAL FORMING BASED ON DUAL RESPONSE SURFACE MODEL

Iterations in optimization and numerical simulation for the sheet metal forming process may lead to extensive computation. In addition, uncertainties in materials or processing parameters may have great influence on the design quality. A six sigma optimization method is proposed, by combining the dual response surface method （DRSM） and six sigma philosophy, to save computation cost and improve reliability and robustness of parts. Using this method, statistical technology, including the design of experiment and analysis of variance, approximate model and six sigma philosophy are integrated together to achieve improved quality. Two sheet metal forming processes are provided as examples to illustrate the proposed method.

Dual-responsive fiber-reinforced hydrogel actuators by direct ion patterning

Nature inspired deformable heterogeneous smart hydrogels have attracted much attention in many fields such as biomedicine devices and soft actuators.However,normal spatial heterogeneous hydrogel structures can only respond to single factor and take one action as set in fabrication.Herein,we report a pre-stretched metal-liganded shape memory hydrogel with fiber reinforced,P(AAc-co-AAm)/CCNFs-Fe3+(CCNFs:carboxylated cellulose nanofibers,AAc:acrylic acid,AAm:acrylamide),which can conduct shape deformation by solvent induction and ultraviolet(UV)light.The deformation pattern could be programmed by the deposing of ferroin ions.Also,the pre-stretched shape memory hydrogels could effectively produce cyclic actuation or complex shape actuation by UV light.More importantly,combining the solvent response with the light response enabled complex reversible actuations,such as simulating the bending and unfolding of fingers.The addition of CCNFs significantly enhanced the mechanical properties of the hydrogels.The hydrogels with 3 wt.%CCNFs showed an elongation at break of about 500%and a significant increase in tensile strength of 8.7-fold to 1.55 MPa after coordination with metal ions,which was able to meet the mechanical requirements of the bionic actuated hydrogels.This work demonstrated that combining light-programmed and light-responsive shape-memory hydrogels,complemented by another independent response property,could achieve complex and reversible programmed actuations.

Self-adaptive hydrogel for breast cancer therapy via accurate tumor elimination and on-demand adipose tissue regeneration

The irregular defects and residual tumor tissue after surgery are challenges for effective breast cancer treatment.Herein,a smart hydrogel with self-adaptable size and dual responsive cargos release was fabricated to treat breast cancer via accurate tumor elimination,on-demand adipose tissue regeneration and effective infection inhibition.The hydrogel consisted of thiol groups ended polyethylene glycol(SH-PEG-SH)and doxorubicin encapsulated mesoporous silica nanocarriers(DOX@MSNs)double crosslinked hyaluronic acid(HA)after loading of antibacterial peptides(AP)and adipose-derived stem cells(ADSCs).A pH-cleavable unsaturated amide bond was pre-introduced between MSNs and HA frame to perform the tumor-specific acidic environment dependent DOX@MSNs release,meanwhile an esterase degradable glyceryl dimethacrylate cap was grafted on MSNs,which contributed to the selective chemotherapy in tumor cells with over-expressed esterase.The bond cleavage between MSNs and HA would also cause the swelling of the hydrogel,which not only provide sufficient space for the growth of ADSCs,but allows the hydrogel to fully fill the irregular defects generated by surgery and residual tumor atrophy,resulting in the on-demand regeneration of adipose tissue.Moreover,the sustained release of AP could be simultaneously triggered along with the size change of hydrogel,which further avoided bacterial infection to promote tissue regeneration.

Robust optimization of the billet for isothermal local loading transitional region of a Ti-alloy rib-web component based on dual-response surface method

Billet optimization can greatly improve the forming quality of the transitional region in the isothermal local loading forming （ILLF） of large-scale Ti-alloy ribweb components. However, the final quality of the transitional region may be deteriorated by uncontrollable factors, such as the manufacturing tolerance of the preforming billet, fluctuation of the stroke length, and friction factor. Thus, a dual-response surface method （RSM）-based robust optimization of the billet was proposed to address the uncontrollable factors in transi- tional region of the ILLF. Given that the die underfilling and folding defect are two key factors that influence the forming quality of the transitional region, minimizing the mean and standard deviation of the die underfilling rate and avoiding folding defect were defined as the objective function and constraint condition in robust optimization. Then, the cross array design was constructed, a dual-RSM model was established for the mean and standard deviation of the die underfilling rate by considering the size parameters of the billet and uncontrollable factors. Subsequently, an optimum solution was derived to achieve the robust optimization of the billet. A case study on robust optimization was conducted. Good results were attained for improving the die filling and avoiding folding defect, suggesting that the robust optimization of the billet in the transitional region of the ILLF was efficient and reliable.

Hyaluronic acid-based dual-responsive nanomicelles mediated mutually synergistic photothermal and molecular targeting therapies

Precise clinical treatment of triple-negative breast cancer(TNBC)is an obstacle in clinic.Nanotechnology-assisted photothermal therapy(PTT)is a superior treatment modality for TNBC in terms of precision.However,thermoresistance arising from PTT and insufficient drug release from nanocarriers decrease the efficacy of PTT.AT13387 is a novel HSP90 inhibitor that can weaken thermoresistance and undergoing clinic II phase study,showing satisfactory antitumour activity through molecularly targeted therapy(MTT).Whereas,it has poor solubility.Hence hyaluronic acid and stearic acid were connected by hydrazone bonds and disulfide bonds,forming an amphipathic copolymer that could self-assembled into nanomicelles,followed by encapsulating Cypate and AT13387.These nanomicelles exhibited great features,including achieving mutually synergistic PTT/MTT for overcoming thermoresistance and promoting translocation of drugs,increasing the solubility of Cypate and AT13387,showing a pH/redox dual response that contributes to drug release,and having the ability of active targeting.Thus,the nanomicelles developed in this study may be a promising strategy for the precise treatment of TNBC.

Self-assembly of supra-amphiphile of azobenzene-galactopyranoside based on dynamic covalent bond and its dual responses

In this paper, dynamic covalent bond has been employed to construct supra-amphiphile of carbohydrate for the first time. In neutral environment, the molecule was fabricated by reacting a hydrophobic building block bearing benzoic aldehyde with a hydrophilic building block bearing hydrazine to form a sugar-containing supra-amphiphile based on acylhydrazone bond, The obtained azobenzene- galactopyranoside （Azo-Gal） supra-amphiphile self-assembled to fibrillar structure in water, which showed dual responses to UV light and pH.

Amphiphilic random polycarbonate self-assemble into GSH/pH dual responsive micelle-like aggregates in water

Responsive polymers have been playing an increasingly important role in a wide variety of applications,such as biomedical materials and biosensors.Herein,we reported a dual-responsive polycarbonate(poly(MN-co-MSS)) based on the macrocyclic Sulfur/Nitrogen-substituted carbonate monomer(MSS/MN) via an enzyme-catalyzed ring-opening copolymerization and Lipase CA Novozym-435 as catalyst,with the disulfide and tertiary amine groups situated on the backbone.The structure of the random copolymers was confirmed by NMR and FTIR.In addition,size exclusion chromatography(SEC) results indicated that the copolymer had a symmetric peak and a relatively narrow polydispersity.Also,the random copolymers can self-assemble into micelle-like aggregates in water due to the hydrophilicity endowed by the amino groups,and the aggregates exhibited rich pH and GSH responsive behavior,which was verified by zeta masters instrument and dynamic light scattering(DLS).Moreover,transmission electron microscopy(TEM) demonstrated the morphology of the micellar aggregates and the variation subjected to the lower pH and GSH,and the responsive mechanism was elaborated.Therefore,these results highlighted a facile synthesis of the environment-responsive polymers and provided a novel GSH/pH responsive material platform for further application.

Coordination-responsive drug release inside gold nanorod @ metal-organic framework core-shell nanostructures for near-infrared-induced synergistic chemo-photothermal therapy

Multifunctional core-shell nanostructures formed by integration of distinct components have received wide attention as promising biological platforms in recent years. In this work, crystalline zeolitic imidazolate framework-8 （ZIF-8）, a typical metal-organic framework （MOF）, is coated onto single gold nanorod （AuNR） core for successful realization of synergistic photothermal and chemotherapy triggered by near-infrared （NIR） light. Impressivel）~ high doxorubicin hydrochloride （DOX） loading capacity followed by pH and NIR light dual stimuli-responsive DOX release can be easily implemented through formation and breakage of coordination bonds in the system. Moreover, under NIR laser irradiation at 808 nm, these novel AuNR@MOF core-shell nanostructures exhibit effective synergistic chemo-photothermal therapy both in vitro and in vivo, confirmed by cell treatment and tumor ablation via intravenous injection.

A highly selective chemosensor for copper ion based on ICT fluorescence

Simple structural compounds 1 to 3 were synthesized.The presence of Cu^（2＋） resulted in the fluorescence and absorption spectra change of 1 and 2,which indicated that 1 and 2 showed a highly selective response to Cu^（2＋） over other metal ions.However,3 showed no selectivity for metal ions,which means that the compound could bind with several metal ions,such as,Ni^（2＋）,Zn^（2＋）,Cd^（2＋）.Hg^（2＋）, Pb^（2＋）,Fe^（3＋）,Mg^（2＋）,Ca^（2＋）,and Co^（2＋）,except Cu^（2＋） and Ag~＋.The different spectral responses were attributed to the difference in binding sites for 1 and 3.

High drug loading polymer micelle@ZIF-8 hybrid core–shell nanoparticles through donor–receptor coordination interaction for pH/H_(2)O_(2)-responsive drug release

Smart drug delivery nanocarriers with high drug loading capacity are of great importance in the treatment of diseases,and can improve therapeutic effectiveness as well as alleviate side effects in patients.In this work,a pH and H_(2)O_(2)-responsive drug delivery platform with high doxorubicin(DOX)loading capacity has been established through coordination interaction between DOX and phenylboronic acid containing block polymer.A composited drug nanocarrier is further fabricated by growing a zeolitic imidazolate framework 8(ZIF-8)on the surface of drug-loaded polymer micelles.The study verifies that ZIF-8 shell can act as intelligent“switch”to prevent DOX leaking from core–shell nanoparticles upon H_(2)O_(2) stimulus.However,a burst drug release is detected upon pH and H_(2)O_(2) stimuli due to the further disassociation of ZIF-8 in acid solution.Moreover,the in vitro anti-cancer experiments demonstrate that the DOX-loaded core–shell nanoparticles provide effective treatment towards cancer cells but have negligible effect on normal cells,which results from the high concentration of H_(2)O_(2) and low pH in the microenvironment of tumor cells.