ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2019
·Vol. 411
·期 17
·3801-3810
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IF 3.286
Huang Yuanlin,Liang Guangzhao,Lin Tianran,Hou Li,Ye Fanggui,Zhao Shulin
The convenience of colorimetric sensors is useful for practical applications. In this work, we constructed a novel colorimetric sensor with magnetic separation ability that can be operated in nearly neutral conditions and achieve one-step detection of metabolites. Magnetic Cu doped Fe 3 O 4 @FeOOH magnetic nanocomposite (Cu/Fe 3 O 4 @FeOOH) with an oxygen vacancy was prepared by a one-step self-assembly hydrothermal method, and fully characterized by different methods. The oxygen vacancy generated by the incorporation of Cu 2+ cations into the Fe 3 O 4 @FeOOH structure was confirmed to be a vital reactive site for enhancing the catalytic activity, which opens up a new way of designing highly efficient enzyme mimics. Benefiting from its inherent horseradish-peroxidase-like activity, a simple and selective enzyme-based colorimetric sensor was developed for one-step detection of H 2 O 2 and cholesterol, and 3,3′,5,5′-tetramethylbenzidine was catalyzed by H 2 O 2 to generate a colored product of oxidized 3,3′,5,5′-tetramethylbenzidine for signaling. H 2 O 2 and cholesterol can be linearly detected in the same range from 0.01 to 0.4 mmol L -1 with detection limits of 0.0075 mmol L -1 and 0.0082 mmol L -1 , respectively. The proposed colorimetric sensor has satisfactory reusability, accuracy, and practicability in human serum samples, indicating its potential application for the detection of different metabolites in the fields of life science and analytical science.
Graphical abstract
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Nanoscale Research Letters
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2019
·Vol. 14
·期 1
·1-10
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IF 3.159
Zheng Qingkai,Cheng Wenjing,Zhang Xiaoping,Shao Runxia,Li Zhongdong
In this report, we present a pH-induced reversible assembly system (PIRAS) based on ferritin (Ft) for targeted tumor therapy. It has been developed to easily load and release of the anticancer drug resveratrol (RV), based on its natural pH-sensitivity and unique hollow cavity of Ft. A tumor-specific target peptide Arg-Gly-Asp (RGD) was conjugated onto the surface of RV-loaded Ft (RV@Ft), to form biocompatible nanoparticles (RV@Ft-RGD). The pH-sensitivity of Ft allows it to be denatured into a hollow porous nanosphere under acidic condition and renatured into a sealed hollow nanosphere under neutral condition. Using pH manipulation, RV@Ft-RGD, with a ~ 21 nm diameter, showed a high RV loading ratio of 79.6%. pH-triggered RV release was then measured at a ratio of 50.3% at pH5.0 over 24 h. Under neutral condition, the RV@Ft-RGD showed excellent stability over 20 days. Confocal fluorescence imaging showed that RV@Ft-RGD had a high cell uptake ratio and co-localization with the lysosome, mainly due to the RGD-mediated target effect. Based on the high drug loading, pH-triggered release, and tumor cell targeting effect, RV@Ft-RGD showed great cell-killing ability in vitro and in vivo. The biocompatibility in vitro and in vivo was also demonstrated to be excellent, without systematic toxicity. The design concept of PIRAS based on Ft significantly inhibits tumor growth and simultaneously further broadens the application of Ft in nanomedicine.
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Acta Biomaterialia
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2016
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IF 6.008
Maohua Chen,Yun Zhang,Zhoujiang Chen,Songzhi Xie,Xiaoming Luo,Xiaohong Li
Challenges remain to load and deliver two or multiple drugs of complementary effects for synergistic cancer therapies. In the current study, multiarmed amphiphilic copolymers of 4-arm poly(ethylene glycol) (PEG) and polyaspartate (PAsp) are created for conjugation of camptothecin (CPT) and condensation with tumor necrosis factor-α (TNF) plasmids. Diethylenetriamine (DET) is grafted on PAsp, and CPT is conjugated onto PAsp(DET) by disulfide linkages to form hydrophobic cores of micelles , followed by condensation with TNF plasmids to form micelleplexes. The cis -aconitic linkers are introduced between PEG and PAsp(DET) to remove PEG shells in response to acidic pH, resulting in destabilized micelleplexes and prompted endosomal escape into the cytosol. The micelleplex disintegration in response to reductive stimuli in the cytosol leads to an efficient CPT release and pDNA disassociation. The co-delivery of CPT with TNF plasmids enhances the gene transfection of micelleplexes at low N/P ratios, and shows synergetic cytotoxicities to tumor cells with 2.5 and 8 folds lower IC 50 s compared with those after treatment with CPT or TNF alone, respectively. The micelleplex treatment on 4T1 tumor models dramatically extends the animal survival and suppresses the tumor growth with 2.3 and 3 folds lower in volume compared with CPT or TNF treatment alone, respectively. Histological and biochemical analyses display TNF expressions in tumor tissues after micelleplex treatment, resulting in significantly larger necrotic regions in tumors, higher cell apoptosis rates , and no obvious sign of tumor metastasis in lungs compared with other treatment. Therefore, the multifunctional micelleplexes based on multiarmed PEG-PAsp(DET) copolymers offer the targeted drug/gene delivery, dually responsive drug/gene release and synergistic antitumor efficacy, holding great promises for combination therapies. Statement of Significance Micelleplexes are constructed from multiarmed amphiphilic copolymers with conjugation of captothecin (CPT) and condensation of tumor necrosis factor-α (TNF) plasmid. The pH/redox stimuli realize co-delivery of CPT and pDNA in a sequential manner of folate-mediated endocytosis , endosomal escape induced by PEG cleavage, reduction-sensitive release of CPT in cytosol, and pDNA release from disintegrated polyplexes after CPT release. Compared with CPT or TNF treatment alone, the micelleplexes achieve 2.5 and 8 folds higher cytotoxicities to tumor cells, and suppress the tumor growth with 2.3 and 3 folds lower in volume, respectively. It demonstrates a feasible strategy to develop multifunctional micelleplexes with simultaneous drug conjugation and pDNA condensation, dually responsive drug/gene release and synergistic antitumor efficacy, holding great promise for combinational therapies.
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CARBOHYDRATE POLYMERS
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2022
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IF 10.723
Shumin Chen,Xiaoguo Ji,Mengyao Zhao,Jiayang Jin,Haiping Zhang,Liming Zhao
AZD9291 can prolong the survival of patients with non-small cell lung cancer. Unfortunately, resistance to AZD9291 is inevitable and hinders effectiveness. Studies showed the combination of Cyclosporin A (CsA) and AZD9291 could increase the efficacy of AZD9291, but the delivery efficiency of free drugs was limited. A chitooligosaccharide (COS) -based nanoparticle with enhanced delivery efficiency and endocytosis was constructed in this study. The results showed that this pH/redox cascade responsive nanoparticles improved therapeutic effect. The system is small and the surface charge changed from negative to positive according to the weakly acidic tumor microenvironment. After endocytosis, the nanoparticles decomposed and released AZD9291 and CsA in redox-rich cytoplasm. Experiments in vitro and in vivo proved that the nanoparticles overcame the biological barrier and significantly enhanced the anti-tumor effect of AZD9291. The novel multifunctional nanoparticle provides a way to overcome the drug resistance and the possibility of clinical application.
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CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Ding Qu,Mengying Jiao,Haijiao Lin,Chunli Tian,Guowei Qu,Jingwei Xue,Lingjing Xue,Caoyun Ju,Can Zhang
Controlled release and tumor-selective distribution are highly desirable for anticancer nanomedicines. Here, we design and synthesize an anisamide-conjugated N -octyl- N,O -maleoyl- O -phosphoryl chitosan (a-OMPC) which can form amphiphilic micelles featuring pH-responsive release and high affinity to sigma-1 receptor-overexpressed tumors for paclitaxel (PTX) delivery. Thereinto, maleoyl and phosphoryl groups cooperatively contribute to pH-responsive drug release due to a conversion from hydrophile to hydrophobe in the acidic microenvironment of endo/lysosomes. We demonstrated that PTX-loaded a-OMPC micelles (PTX-aM) enhanced the cellular internalization via the affinity between anisamide and sigma-1 receptor, rapidly released drug in endo/lysosomes and elevated the cytotoxicity against PC-3 cells. The in vivo studies further verified that PTX-aM could largely accumulate at the tumor site even after 24 h of administration, resulting in obvious inhibition effect and prolonged survival period in PC-3 tumor xenograft-bearing mice. Moreover, OMPC showed no obvious hemolytic and acute toxicity. Collectively, this chitosan derivate holds a promising potential in application of prostate cancer-targeted drug delivery system.
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BIOSENSORS & BIOELECTRONICS
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2014
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IF 6.451
Changqin Ding,Yang Tian
The dysregulated pH is working as a mark of cancer. It is a challenge for developing a biosensor for targeted imaging in cancer cells and monitoring of intracellular pH . Here, a ratiometric fluorescence biosensor for pH determination was developed with targeted imaging into folate acceptor (FR)-rich cancer cells at the same time. AuNCs protected by bovine serum albumin (BSA) worked as reference fluorophore and fluorescein-isothiocyanate (FITC) acted as the response signal for pH. For targeted imaging of cancer cells, the AuNCs were simultaneously conjugated with folic acid (FA). The developed ratiometric biosensor can monitor pH with a wide linear range from 6.0–7.8 with a pKa at 6.84. Under every different pH condition , the probe showed high selectivity over various metal ions and amino acids with its fluorescence ratio stayed almost constant (<5%). It also showed good cyclic accuracy when pH switched between 6.0 and 8.0, as well as low cytotoxicity. The AuNC-based inorganic–organic nanohybrid biosensor showed good cell-permeability, low cytotoxicity, and long-term photostability. Accordingly, the pH biosensor was employed to gain targeted imaging in FR +ve Hela cells with FR −ve lung carcinoma cells A549 as comparison, and achieved to monitor the pH changes in Hela cells.
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Biomaterials Science
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2020
·Vol. 8
·期 20
·5739-5750
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IF 6.183
Sihui Wei,Guilan Quan,Chao Lu,Xin Pan,Chuanbin Wu
Photothermal therapy (PTT) based on aggregation-induced emission luminogen (AIEgen) is very promising for superficial tumor therapy due to the superior photostability and photothermal conversion efficiency of AIEgens. However, the systemic administration of AIEgen remains challenging, mainly because of solubility dissatisfaction and biodistribution. Here, a dissolving microneedle (MN) system loaded with AIEgen (NIR950) was developed for topical administration to treat malignant skin tumor melanoma. Firstly, NIR950-loaded polymeric micelles (NIR950@PMs) were prepared via a nanoprecipitation method to increase the drug solubility. Then, micelles were concentrated on needle tips of MN (NIR950@PMs@MN) by a two-step molding method. NIR950@PMs showed no distinct decline in emission intensity under continuous laser irradiation for an hour. Moreover, the pH-responsive micelles can be protonated in an acidic tumor microenvironment to facilitate the intracellular uptake. By virtue of dissolving MN, NIR950@PMs could rapidly accumulate at the tumor site and reach a suitable temperature for killing cancer cells under laser irradiation. With only single administration and one-time laser irradiation, the NIR950@PMs@MN could notably eliminate melanoma tumors with a low dose of NIR950. Overall, this dissolving MN system loaded with NIR950 showed remarkable photostability and also achieved a valid photothermal effect, which indicate great potential for clinical superficial tumor therapy.
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INTERNATIONAL JOURNAL OF HYDROGEN ENERGY
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2020
·
IF 4.939
Ruisong Li,Feng-Yi Zheng,Xiaohan Zhang,Jiadan Hu,Congying Xu,Yucang Zhang
Various catalysts were synthesized by incorporating phosphorus and iron into nitrogen-containing carbon derived from shrimp shell with pyrolysis . These catalysts had high specific surface area, uniform atomic doping and various active sites, which resulted in the high kinetics activity towards oxygen reduction reaction (ORR) under various pH conditions . Based on different doping sources to analyse ORR activity, phosphorus-doped catalyst was suitable for alkaline medium and iron doping for acidic medium, while their synergistic effect induced the highest ORR activity in neutral medium. Besides, the stability measurements investigated their abilities for application. Introducing iron into nitrogen-containing carbon could gradually strengthen the long-term stability for different catalysts in various pH conditions. Especially, phosphorus doping promoted the best ORR performance in alkaline condition with an extremely poor stability, which could be overcome by further adding iron. This work provides a strategy for the doped biomass-based carbon to accommodate different fuel cells.
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FOOD HYDROCOLLOIDS
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2017
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IF 4.747
Enmin Chen,Shan Wu,David Julian McClements,Bin Li,Yan Li
Cinnamaldehyde (CA), a common hydrophobic flavor, was encapsulated in oil-in-water emulsions that were stabilized by whey protein isolate (WPI). The impact of CA content and pH on the physical stability and lipolysis of the emulsions was then investigated. The presence of CA gave the emulsions a creamy yellow color, which became darker during storage. Emulsions formed using only CA as the oil phase contained large droplets that were physically unstable to particle growth and phase separation. The addition of medium chain triglyceride oil (MCT) improved the stability of emulsions containing CA, which was attributed to inhibition of Ostwald ripening effects. Fluorescent microscopy indicated that the adsorption of the protein to the droplet surfaces led to a thicker adsorbed layer in the presence of CA. The stability of the emulsions to droplet flocculation and coalescence depended on the CA level in the oil phase and the pH of the aqueous phase. An in vitro model was used to assess the impact of oil phase composition and pH on lipid hydrolysis and emulsion microstructure under simulated gastrointestinal tract conditions. The rate of lipid hydrolysis was highly dependent on CA level and pH. These results may facilitate the fabrication of emulsions with controlled GIT fate that are suitable for use in functional foods and beverages.
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MOLECULAR PHARMACEUTICS
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2020
·
IF 4.321
Ying-Zheng Zhao,Meng-Ting Lin,Qing-Hua Lan,Yuan-Yuan Zhai,He-Lin Xu,Jian Xiao,Longfa Kou,Qing Yao
Disulfiram (DSF) is an FDA-approved anti-alcoholic drug that has recently proven to be effective in cancer treatment. However, the short half-life in the bloodstream and the metal ion-dependent antitumor activity significantly limited the further application of DSF in the clinical field. To this end, we constructed a silk fibroin modified disulfiram/zinc oxide nanocomposites (SF/DSF@ZnO) to solubilize and stabilize DSF, and, more importantly, achieve pH triggered Zn2+ release and subsequent synergistic antitumor activity. The prepared SF/DSF@ZnO nanocomposites were spherical and had a high drug loading. Triggered by the lysosomal pH, SF/DSF@ZnO could induce the rapid release of Zn2+ under the acidic conditions and caused nanoparticulate disassembly along with DSF release. In vitro experiments showed that cytotoxicity of DSF could be enhanced by the presence of Zn2+, and further amplified when encapsulated into SF/DSF@ZnO nanocomposites. It was confirmed that the significantly amplified cytotoxicity of SF/DSF@ZnO was resulted from pH-triggered Zn2+ release, inhibited cell migration, and increased ROS production. In vivo study showed that SF/DSF@ZnO nanocomposites significantly increased the tumor accumulation and prolonged the retention time. In vivo antitumor experiments in the xenograft model showed that SF/DSF@ZnO exerted the highest tumor-inhibition rate among all the drug treatments. Therefore, this exquisite study established silk fibroin-modified disulfiram/zinc oxide nanocomposites, SF/DSF@ZnO, where ZnO not only acted as a delivery carrier but also served as a metal ion reservoir to achieve synergistic antitumor efficacy. The established DSF nanoformulation displayed excellent therapeutic potential in future cancer treatment.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2020
·
IF 3.99
Hongzhi Gu,Qingwei Huang,Jinli Zhang,Wei Li,Yan Fu
Heparin serves as both reductant and stabilizer for biogenic synthesis of ultrasmall Pt nanoclusters. The surface remaining heparin enhances the affinity of Pt nanoclusters with the substrate 3,3′,5,5′-tetramethylbenzidine, thereby contributing to outstanding peroxidase mimicking activity in near-neutral media. Heparin-reduced Pt nanoclusters exclusively exhibit peroxidase mimicking activities without oxidase-like characteristics. The most efficient Pt nanozyme was reduced at 80 °C by adopting the [K 2 PtCl 4 ]/[heparin] of 1, showing the K m of 165 mM for H 2 O 2 and 0.016 mM for TMB. This developed Pt nanozyme displays a marked superior in both peroxidase-like activity and peroxidase specificity under near-neutral environment over previously reported Pt nanozymes. Based on these two considerable features of heparin-Pt nanozyme, a colorimetric test was developed for directly monitoring glucose at pH 6. This work proposes an efficient way to construct peroxidase mimetics at near-physiological pH without the interference of dissolved oxygen.
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SCIENCE AND TECHNOLOGY OF ADVANCED MATERIALS
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2019
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IF 3.585
Jiajie Chen,Jiaxing Liu,Yaping Hu,Zhengfang Tian,Yufang Zhu
In nanoplatform-based tumor treatment, combining chemotherapy with hyperthermia therapy is an interesting strategy to achieve enhanced therapeutic efficacy with low dose of delivery drugs. Compared to photothermal therapy, magnetic hyperthermia has few restrictions on penetrating tissue by an alternating magnetic field, and thereby could cure various solid tumors, even deep-tissue ones. In this work, we proposed to construct magnetic nanocomposites (Fe3O4@PDA@ZIF-90) by the external growth of metal-organic framework ZIF-90 on polydopamine (PDA)-coated Fe3O4 nanoparticles for synergistic magnetic hyperthermia and chemotherapy. In such multifunctional platform, Fe3O4 nanoparticle was utilized as a magnetic heating seed, PDA layer acted as an inducer for the growth of ZIF-90 shell and porous ZIF-90 shell served as drug nanocarrier to load doxorubicin (DOX). The well-defined Fe3O4@PDA@ZIF-90 core-shell nanoparticles were displayed with an average size of ca. 200 nm and possessed the abilities to load high capacity of DOX as well as trigger drug release in a pH-responsive way. Furthermore, the Fe3O4@PDA@ZIF-90 nanoparticles can raise the local temperature to meet hyperthermia condition under an alternating magnetic field owing to the magnetocaloric effect of Fe3O4 cores. In the in vitro experiments, the Fe3O4@PDA@ZIF-90 nanoparticles showed a negligible cytotoxicity to Hela cells. More significantly, after cellular internalization, the DOX-loaded Fe3O4@PDA@ZIF-90 nanoparticles exhibited distinctively synergistic effect to kill tumor cells with higher efficacy compared to chemotherapy or magnetic hyperthermia alone, presenting a great potential for efficient tumor therapy.
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