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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

pH and redox dual-responsive ZIF-8-based nanoplatform for targeted pathogens and environmental protection

Shuhui Hu,Lin-Lin Yang,Chang Yan,Yanan Xiao,Zijing Jin,Xiuhai Gan,Bo Zhang,Wenneng Wu

Environmental stimulus-responsive controlled-release nanopesticides have the ability to adapt to the specific microenvironment of pathogen outbreaks, which can improve pesticide utilization efficiency. A pH and redox dual-stimuli responsively controlled release system (ZIF-8@Hex@Fe/GA) using zeolitic imidazolate framework-8 (ZIF-8) as the support and metal-phenol complex (Fe-GA) as the capping agent was constructed to deliver hexaconazole (Hex) for management of Phomopsis sp. The ZIF-8@Hex@Fe/GA composite demonstrated a high loading capacity and effectively improved the light stability of Hex. The hydroxyl groups present in the composite facilitate its diffusion on kiwifruit leaves, improving wettability. Additionally, the large specific surface area of ZIF-8@Hex@Fe/GA provides resilience against rainwater scouring. This innovative system intelligently responds to the acidic and oxidizing conditions associated with Phomopsis sp. infections, ensuring targeted and controlled release of Hex. Bioactivity assessments revealed that ZIF-8@Hex@Fe/GA exhibited protective effects of 84.16 ± 3.37 % and 80.77 ± 2.08 % on kiwifruit fruits and leaves at a concentration of 100 mg/L, outperforming Hex emulsifiable concentrate (Hex EC) by 21.34 % and 25.39 %, respectively. The acute toxicity of ZIF-8@Hex@Fe/GA to zebrafish was reduced 9-fold compared to Hex EC. Furthermore, ZIF-8@Hex@Fe/GA showed high safety for HEK293 cells, with a cell survival rate of 81.59 ± 2.11 % after 72 h of 10 mg/L treatment, whereas the cell survival rate for Hex TC, treatment was only 1.79 ± 1.32 % after 72 h. In conclusion, ZIF-8@Hex@Fe/GA demonstrates significant potential for targeted pesticide delivery and environmental protection.

CAS / MDL: 693-98-1
研究领域: 植物病理学 · 环境科学 · 材料科学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2022 ·Vol. 23 ·期 13 ·7342 · IF 6.208

Dually Responsive Nanoparticles for Drug Delivery Based on Quaternized Chitosan

Fenghui Qiao,Zhiqi Jiang,Wen Fang,Jingzhi Sun,Qiaoling Hu

In this work, we report the fabrication and functional demonstration of a kind of dually responsive nanoparticles (NPs) as a potential drug delivery vector. The pH value, corresponding to the acidic microenvironment at the tumor site, and mannitol, to the extracellular trigger agent, were employed as the dually responsive factors. The function of dual responses was achieved by breaking the dynamic covalent bonds between phenylboronic acid (PBA) groups and diols at low pH value (pH 5.0) and/or under the administration of mannitol, which triggered the decomposition of the complex NPs and the concomitant release of anticancer drug of doxorubicin (DOX) loaded inside the NPs. The NPs were composed of modified chitosan (PQCS) with quaternary ammonium and PBA groups on the side chains, heparin (Hep), and poly(vinyl alcohol) (PVA), in which quaternary ammonium groups offer the positive charge for the cell-internalization of NPs, PBA groups serve for the formation of dynamic bonds in responding to pH change and mannitol addition, PVA furnishes the NPs with diol groups for the interaction with PBA groups and the formation of dynamic NPS, and Hep plays the roles of reducing the cytotoxicity of highly positively-charged chitosan and forming of complex NPs for DOX up-loading. A three-step fabrication process of drug-loaded NPs was described, and the characterization results were comprehensively demonstrated. The sustained drug release from the drug-loaded NPs displayed obvious pH and mannitol dependence. More specifically, the cumulative DOX release was increased more than 1.5-fold at pH 5.0 with 20 mg mL−1mannitol. Furthermore, the nanoparticles were manifested with effective antitumor efficient and apparently enhanced cytotoxicity in response to the acidic pH value and/or mannitol.Keywords:chitosan;drug delivery;nanoparticle;dual response;dynamic bond

研究领域: 生物材料学 · 药剂学 · 肿瘤学
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JOURNAL OF APPLIED POLYMER SCIENCE · 2019 ·Vol. 136 ·期 47 ·48247 · IF 2.188

Chitosan-based double network hydrogels with self-healing and dual-responsive shape memory abilities

Beijia Fu,Baoxiao Cheng,Xiaoqiang Jin,Xiaojiong Bao,Zhengke Wang,Qiaoling Hu

Chitosan-based single network hydrogels with imine bonds have excellent self-healing capability, while poor mechanical properties limit their applications. Here, chitosan-polyacrylamide-based double network hydrogels were prepared via in situ free-radical polymerization of acrylamide in the presence of N -carboxyethyl chitosan (CEC) and dibenzaldehyde-terminated telechelic poly(ethylene glycol), which had excellent mechanical properties, self-healing, and dual-responsive shape memory abilities. The maximum tensile strength and elongation at break could reach 460 kPa and 4600%, respectively. Meanwhile, owing to the reversibility of imine bonds, elongation and strength at break of hydrogels could heal by 84.2 and 93.2% under alkali stimulation at 35 °C, respectively. Furthermore, the hydrogels also had good shape memory abilities for pH-stimuli responsiveness of the imine bonds and metal ions stimuli responsiveness of CEC. The prepared chitosan-based functional hydrogels have great potential application prospects in tissue scaffolds, actuators, and wearable devices. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136 , 48247.

研究领域: 材料科学 · 生物医学工程
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BIOMACROMOLECULES · 2016 · IF 5.583

Double-Cross-Linked Hyaluronic Acid Nanoparticles with pH/Reduction Dual-Responsive Triggered Release and pH-Modulated Fluorescence for Folate-Receptor-Mediated Targeting Visualized Chemotherapy

Xubo Zhao,Xu Jia,Lei Liu,Jin Zeng,Kun Tian,Tingting Zhou,Peng Liu

A versatile folate-receptor-mediated targeting tumor theranostics has been designed for pH/reduction dual-responsive controlled anticancer drug release and pH-modulated fluorescent tumor imaging via facile ionic (pH sensitive) and covalent (reduction responsive) double-cross-linking (DCL) of the folic acid (FA) and Rhodamine 6G modified hyaluronic acid (HA) (FA-HA-Rh 6G). After optimizing the morphology and diameter of the resultant nanoparticles (DCL FA-HA-Rh 6G NPs) via modulating the concentration of the ionic and covalent cross-linking agents, the one with Ca and S contents of 1.70 and 2.84 wt % and an average hydrodynamic diameter of 154 nm was chosen as the desired drug delivery system (DDS) for DOX. They not only had high drug loading capacity and drug encapsulation efficiency (716 ± 34 mg/g and 71.6 ± 3.4%) but also possessed perfect triggered release and strong fluorescence intensity in the stimulated tumor microenvironment. The MTT assay and CLSM analysis revealed that the proposed double-cross-linked HA-based DDS had favorable cytocompatibility and folate-receptor-mediated targeting functionality to the HeLa cells and could obviously enhance the anticancer efficiency of DOX. The integration of the pH and reduction dual-responsiveness, folate-receptor-mediated targeting functionality, and pH-dependent fluorescence intensity into the biodegradable and biocompatible HA nanoparticles make the DCL FA-HA-Rh 6G NPs significant potential for future visualized chemotherapy of cancers.

CAS / MDL: 6066-82-6
研究领域: 生物材料 · 纳米医学 · 肿瘤学
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POLYMER · 2020 · IF 4.231

Facile preparation of pH/reduction dual-stimuli responsive dextran nanogel as environment-sensitive carrier of doxorubicin

Kun Yu,Xiyao Yang,Lihua He,Rong Zheng,Jie Min,Hongying Su,Shaoyun Shan,Qingming Jia

Dual and multi-stimuli responsive polymeric nanoparticles that can respond to two or more signals have been demonstrated as prospective drug carriers with enhanced tumor accumulation and on-demand drug release profiles. In this study, dextran-based (Dex-SS) nanogels were developed via a facile method based on the disulfide containing Schiff base formation between polyaldehyde dextran and cystamine in water-in-oil inverse microemulsion . Acidic and reductive (GSH) environment sensitive degradation behaviors of the resulted nanogels were investigated by morphology analysis of the treated nanogels using SEM imaging. Doxorubicin (DOX) was covalently conjugated into the dextran nanogels via Schiff base linkages, and pH/GSH dual sensitive drug release profiles were demonstrated. Effective cell uptake of the DOX-loaded nanogels was finally identified by human cancer cell line of H1299. Take advantage of the acidic and reductive tumor microenvironment, the dual-stimuli responsive Dex-SS nanogels can serve as microenvironment-sensitive drug delivery systems for tumor therapy.

研究领域: 药剂学 · 生物材料学 · 肿瘤学
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2024 · IF 4.9

pH- and temperature-dual responsive polymer emulsion for rapid release of drag reducer

Yong Zhang,Caifu Zhi,Jie Qi,Yang Wu,Li Wang,Shanshan Dai,Hongsheng Lu

Slick water fracturing fluid is widely used in major oil fields due to its low cost and high drag reduction. Polyacrylamide emulsions drag reducers play a decisive role in slick water fracturing. The dissolution rate of polymer emulsions drag reducers was increased by adding hydrophilic surfactants, but the stability of the emulsions is poor, which limits its wide application. In order to solve the contradiction between the stability of polymer emulsion and rapid release of drag reducer. Here, a P(AA-AM-AMPS) polymer emulsion drag reducer with dual stimulation response of pH and temperature was designed. Surfactant (D400/OA) with dual responses to pH and temperature is synthesized by using oleic acid (HOA) and polyether amine 400 (D400). D400/OA shows a remarkable pH- and temperature-responsive behavior due to the pH- and temperature-induced structural transformation of D400/OA. Interestingly, D400/OA-stabilized monomer emulsion exhibits an obvious pH- and temperature-induced structural transformation. Meanwhile, The D400/OA-stabilized monomer emulsion has remarkable stability, which benefits the inverse emulsion polymerization of P(AM-AA-AMPS) polymer. The obtained P(AM-AA-AMPS) polymer emulsion maintain stability whose particle size nearly unchanged by storing for 15 days. Interestingly, P(AM-AA-AMPS) polymer emulsion can be released completely by changing the pH or temperature of the aqueous solution. The apparent viscosity of P(AM-AA-AMPS) polymer, in either the alkaline (pH=10.31) solution of 25±2 °C or neutral (pH=7) solution of 70±2 °C, respectively required 40 s and 8 min to reached a maximum value of 96 mPa·s. The release rate of P(AM-AA-AMPS) polymer emulsion is further enhanced under the dual responsive of temperature (70±2 ℃) and pH (10.31) and it takes only 20 s, In addition, the drag reduction rate of P(AM-AA-AMPS) polymer emulsion is 72 % when completely released under the dual responsive of temperature and pH, showing a remarkable drag reduction property. The D400/OA-stabilized P(AM-AA-AMPS) polymer emulsion are expected to meet the demand for the production enhancement of the oil and gas reservoirs.

研究领域: 材料科学 · 石油工程
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Materials · 2020 ·Vol. 13 ·期 6 ·1279 · IF 3.057

pH and Redox Dual-Responsive MSN-S-S-CS as a Drug Delivery System in Cancer Therapy

Yanqin Xu,Liyue Xiao,Yating Chang,Yuan Cao,Changguo Chen,Dan Wang

In order to achieve a controlled release drug delivery system (DDS) for cancer therapy, a pH and redox dual-responsive mesoporous silica nanoparticles (MSN)-sulfur (S)-S- chitosan (CS) DDS was prepared via an amide reaction of dithiodipropionic acid with amino groups on the surface of MSN and amino groups on the surface of CS. Using salicylic acid (SA) as a model drug, SA@MSN-S-S-CS was prepared by an impregnation method. Subsequently, the stability, swelling properties and drug release properties of the DDS were studied by x-ray diffraction, scanning electron microscopy, Fourier transform infrared microspectroscopy, size and zeta potential as well as Brunauer–Emmett–Teller surface area. Pore size and volume of the composites decreased after drug loading but maintained a stable structure. The calculated drug loading rate and encapsulation efficiency were 8.17% and 55.64%, respectively. The in vitro drug release rate was 21.54% in response to glutathione, and the release rate showed a marked increase as the pH decreased. Overall, double response functions of MSN-S-S-CS had unique advantages in controlled drug delivery, and may be a new clinical application of DDS in cancer therapy.Keywords:mesoporous silica nanoparticles;double response;drug delivery;drug release

研究领域: 生物材料学 · 癌症治疗 · 纳米医学
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RSC Advances · 2022 ·Vol. 12 ·期 7 ·3871-3882 · IF 4.036

DNA aptamer-based dual-responsive nanoplatform for targeted MRI and combination therapy for cancer

Mingming Zhao,Xiaoxi Song,Jiahui Lu,Siwen Liu,Xuan Sha,Qi Wang,Xu Cao,Kai Xu,Jingjing Li

Accurate drug delivery is a common topic, and it has always been an aim that scientists strive to achieve. To address this need, multifunctional and stimulus-sensitive nanoplatforms have attracted significant attention. Here we fabricated a glutathione (GSH) and adenosine-5′-triphosphate (ATP) dual-sensitive nanoplatform for controlled drug release and activatable MRI of tumors based on DNA aptamer and manganese dioxide (MnO2) nanosheets. Cleverly utilizing the DNA tunability, AS1411 aptamer which binds nucleolin, a protein specifically expressed on tumor-associated endothelial cells, was designed with ATP aptamer and its cDNA to load the anticancer drug, doxorubicin (Dox). The formed DNA-Dox complex was delivered to the tumor region with the help of MnO2 nanosheets and AS1411 aptamer. Then, the on-demand drug release in tumor cells was realized with the co-effect of the ATP aptamer and GSH reduction. It was found that without the structure of the MnO2 nanosheets being broken by GSH, Dox almost could not be released even in the presence of ATP. Similarly, without ATP, Dox was still maintained in the duplex even with GSH. Further combining the MRI ability and chemodynamic therapy of the produced Mn2+, an improved effect of the inhibition of tumor growth and imaging was achieved. Our designed DNA aptamer-based dual-responsive nanoplatform can realize the targeted drug delivery and MRI of breast tumor cells both in vitro and in vivo.

研究领域: 生物医学工程 · 肿瘤学 · 纳米医学
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BIOMACROMOLECULES · 2021 · IF 6.988

Poly(l-cysteine) Peptide Amphiphile Derivatives Containing Disulfide Bonds: Synthesis, Self-Assembly-Induced β-Sheet Nanostructures, pH/Reduction Dual Response, and Drug Release

Liang Dong,Hui Chen,Ting Liu,Junming Zhu,Min Yu,Qingmei Yuan

Three disulfide bond-containing peptide amphiphiles (PA1–3) with different lengths of alkyl tails (PA1 for C6, PA2 for C12, and PA3 for C18) were synthesized by ring-opening polymerization of α-amino acid N-carboxyanhydride followed by post-polymerization modification. The peptide segments were composed of 3-mercaptopropionic acid-modified poly(l-cysteine) [P(Cys-SS-CH2CH2COOH)]. We characterized the chemical structure and molecular parameters by 1H NMR, 13C NMR, gel permeation chromatography, Fourier transform infrared spectroscopy, and circular dichroism spectroscopy. It is found that alkyl-P(Cys-SS-CH2CH2COOH) mainly presents a β-sheet conformation at the solid state. However, the PAs present predominant random coils at pH 7.4 in aqueous solutions. The β-sheet conformation increased dramatically when the concentration of the PA exceeded its critical micelle concentration (ca. 0.3 mg/mL for PA3), indicating the formation of self-assembly-induced β-sheet nanostructures. Elongation of the alkyl chain length or a decrease of the pH of the PA solution can promote the formation of the β-sheet conformation. The three PAs can self-assemble into spherical micelles or nanofibrous hydrogels, which can be utilized as nanocarriers for systemic drug delivery or implants for localized drug delivery, respectively. Cisplatin (CDDP) was loaded as a model medicine to examine the drug delivery potential of PA3. We found that the CDDP-loaded PA3 micelles are stable at pH 7.4, have a spherical morphology with a hydrodynamic diameter of ca. 52 nm, and accomplish pH/reduction dual-responsive release of CDDP. In addition, alkyl-P(Cys-SS-CH2CH2COOH) can self-assemble into nanofibrous hydrogels at pH 5.0–6.0 or upon the addition of certain metal ions and show excellent dynamic reversibility. Moreover, the CDDP-loaded PA3 hydrogel exhibits a sustained release profile and a nearly linear release over 48 h. In vitro cytotoxicity of PA3 also indicates its nontoxicity. Thus, our findings suggest that alkyl-P(Cys-SS-CH2CH2COOH) has great potential for both systemic and localized delivery of therapeutics.

研究领域: 生物材料学 · 药剂学 · 纳米医学
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JOURNAL OF MOLECULAR LIQUIDS · 2020 · IF 5.065

Self-assembly and in vitro drug release behaviors of amphiphilic copolymers based on functionalized aliphatic liquid crystalline polycarbonate with pH/temperature dual response

Xiaofeng Liu,Zhihao Guo,Tiejun Ge,Jianshe Hu,Jiwei Wang,Liqun Yang

Amphiphilic copolymers Pn (n = 1–3) with mPEG as hydrophilic segment and aliphatic polycarbonate as hydrophobic segment were designed and synthesized successfully, and the results of POM, XRD and DSC showed that only P3 showed liquid crystalline (LC) phase. Due to the carboxyl and cholesteric LC groups in the side chain of the polycarbonate, the micelles prepared in this study were endowed with pH and temperature dual response. The effects of different conditions such as selective solvents, copolymer concentration, pH, temperature, the structure and LC mesophase on the self-assembly behavior and drug loading properties of the copolymer micelles were explored. It was found that the critical water concentration for self-assembly, the particle size and morphology of the micelles could be effectively controlled by changing the above conditions. Moreover, introducing LC properties into the copolymer could effectively decrease the critical water concentration for self-assembly and elevate the drug loading content. The DOX was conjugated to the copolymers by hydrogen bonds , and the copolymer P3 could form regular fusiform micelles after loading with DOX. Moreover, P3-DOX micelles could be endocytosed into cells and the drug release behavior could be triggered by the weak acid condition and elevated temperature. Therefore, the P3-DOX micelles could achieve a pH-triggered rapid drug release under weakly acidic conditions of the tumor cells. This kind of controllable micelles will have a potential application as drug-carriers in drug delivery.

CAS / MDL: 538-75-0
研究领域: 生物材料学 · 药剂学
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CARBOHYDRATE POLYMERS · 2018 · IF 5.158

One-pot fabrication of pH/reduction dual-stimuli responsive chitosan-based supramolecular nanogels for leakage-free tumor-specific DOX delivery with enhanced anti-cancer efficacy

Jiagen Li,Peng Liu

Facile one-pot approach was established to fabricate chitosan-based supramolecular nanogels as pH/reduction dual-stimuli responsive drug delivery system (DDS) for anticancer drug (doxorubicin, DOX), by bioreducible crosslinking of the β -cyclodextrin modified chitosan (CD-CS) with disulfide bond embedded crosslinker (Ad-SS-Ad) via host-guest inclusion and simultaneous DOX loading. The DOX@Ad-SS-Ad/CD-CS supramolecular nanogels with hydrodynamic diameter ( D h ) of 140 nm and drug-loading capacity of 15.9% were obtained with the mass feeding ratio of carrier:DOX at 25:10. They were stable in the simulated physiological medium with premature drug release of only 3% over 60 h, while a high cumulative release up to 82.3% was achieved within 84 h in a sustained manner without initial burst in the simulated tumor intracellular micro-environment. The MTT assays indicated that the blank Ad-SS-Ad/CD-CS supramolecular nanogels were cytocompatible, while the proposed DOX@Ad-SS-Ad/CD-CS supramolecular nanogels possessed the enhanced antitumor efficacy in comparison with the free DOX.

研究领域: 药剂学 · 生物材料 · 肿瘤学
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2016 · IF 3.994

Coordinated pH/redox dual-sensitive and hepatoma-targeted multifunctional polymeric micelle system for stimuli-triggered doxorubicin release: Synthesis, characterization and in vitro evaluation

Lele Wang,Baocheng Tian,Jing Zhang,Keke Li,Yan Liang,Yujie Sun,Yuanyuan Ding,Jingtian Han

Multifunctional polymeric micelles self-assembled from a DOX-conjugated methoxypolyethylene glycols- b -poly (6- O -methacryloyl- d -galactopyranose)-disulfide bond-DOX (mPEG- b -PMAGP-SS-DOX) copolymer were prepared as an antitumor carrier for doxorubicin delivery, of which the chemical modification with disulfide bonds and hydrazone bonds allowed micelles to release doxorubicin (DOX) selectively at acidic pH and high redox conditions. The resulting micelles exhibited coordinated pH/redox dual-sensitive and hepatoma-targeted multifunction with sustaining stability in aqueous media. The multifunctional micelles showed spherical shapes with a mean diameter of 93   ±   2.08   nm, a low polydispersity index (PDI) of 0.21, a low CMC value of 0.095   mg/mL, a high drug grafting degree of 56.9% and a drug content of 39.0%. Remarkably, in vitro drug release studies clearly exhibited a pH and redox dual-sensitive drug release profile with significantly accelerated drug release treated with pH 5.0 and 10   mM GSH (88.4% in 72   h) without drug burst release. The tumor proliferation assays indicated that DOX-grafted micelles, along with low cytotoxicity and well biocompatibility to normal cells up to a concentration of 10   μg/mL, inhibited the proliferation of HepG2 cells in a formulation-, time- and concentration-dependent manner in comparison with MCF-7 cells which was similar to free DOX. Anticancer activity releaved that the disulfide-modified micelles possessed much higher anti-hepatoma activity with a low IC 50 value of 1.1   μg/mL following a 72   h incubation. Furthermore, the intracellular uptake tested by CLSM and FCM demonstrated that multifunctional polymeric micelles could be more efficiently taken up by HepG2 cells compared with MCF-7 cells, agreed well with MTT assays, suggesting these well-defined micelles provide a potential drug delivery system for dual-responsive controlled drug release and enhanced anti-hepatoma therapy.

研究领域: 药剂学 · 肿瘤学 · 生物材料学
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