COLLOIDS AND SURFACES B-BIOINTERFACES
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2021
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IF 5.268
Ning Wang,Chenyu Liu,Weihe Yao,Hengjun Zhou,Simiao Yu,Hailiang Chen,Weihong Qiao
Constructing highly efficient and multifunctional nanoparticles to overcome the multiple challenges of targeted drug delivery is a new strategy urgently needed in tumor therapy. Here, we synthesized pH-responsive prodrug ( PEG 2K -NH -N- DOX ), GSH-responsive prodrug ( PEG 2K -S-S-CPT ), folate-receptor targeting polymers ( FA-PEG 2K -L8 , FA-PEG 2K -TOS) and T1-enhanced magnetic resonance imaging contrast agents ( Gd-DTPA-N16−16) , used to encapsulate combrestatinA4 (CA4) to prepare multifunctional nanoparticles ( FTDCAG NPs). Unlike other nanoparticles, FTDCAG NPs contains three drugs with the ability to control the release in time and space, which can maximize the effectiveness of precise cancer chemotherapy. We first confirmed that specific binding between FTDCAG NPs and overexpressed folate-receptor cells by flow cytometry and confocal laser scanning microscopy. We then investigated the spatiotemporally controlled release ability of FTDCAG NPs loaded with doxorubicin (DOX), CA4 and camptothecin (CPT). Relative to pH = 7.4, the release efficiency of CA4 in the pH = 6.5 increased by 63.4 %. The first released CA4 is able to destroy the angiogenesis and help tumor cells to be exposed to the remaining FTDCG NPs. After being internalized into the tumor cells, FTDCG NPs is disassembled and the CPT and DOX were released due to the increase of intracellular GSH concentration and the decrease of pH value. Besides, the relaxation time of FTDCAG NPs is 3.86 times that of clinical Gd-DTPA, and the in vitro and vivo T1-weighted imaging is brighter, which can be used to trace the nanoparticles by MRI. Therefore, FTDCAG NPs provide an efficient strategy for the design of multifunctional drug delivery systems for enhancing antitumor efficacy.
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Frontiers in Chemistry
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2021
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IF 5.221
Li Jianwen,Zhang Zhanxia,Deng Haibin,Zheng Zhan
Cinobufagin is used as a traditional Chinese medicine for cancer therapy. However, it has some disadvantages, such as poor water solubility, short circulating half-life, and low bioavailability. In the present study, a targeted delivery and smart responsive polydopamine (PDA)-based nanomedicine for delivering cinobufagin was rationally designed to improve the anticancer efficacy of the compound for the treatment of lung cancer. The modification of the nanomedicine using folic acid first mediated tumor targeting via the interaction between folic acid and its receptors on tumor cells. After lysosomes escape, the PDA nanomedicine was triggered by the low pH and released its cargo into the tumor microenvironment. The nanomedicine had a better therapeutic effect against lung cancer when used in combination with photothermal therapy. Compared with other nanomedicines used with photothermal therapy, this nanocarrier was not only sensitive to biologically low pH levels for on-demand drug release, but was also biodegradable, breaking down into biocompatible terminal products. Therefore, the proposed drug delivery system with targeted delivery and smart release demonstrated potential as a multifunctional nanoplatform that can enhance the bioavailability and reduce the side effects of chemotherapeutic agents.
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ACS Applied Materials & Interfaces
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2021
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IF 9.229
Yiting Jiang,Minxuan Sun,Nan Ouyang,Yuguo Tang,Peng Miao
Herein, we develop a novel and effective combination nanoplatform for cancer theranostics. Folic acid (FA) is first modified on the photothermal agent of polydopamine (PDA), which possesses excellent near-infrared (NIR) absorbance and thermal conversion features. Temperature-sensitive silver nanoclusters (AgNCs) are then synthesized on the DNA template that also loads the anticancer drug doxorubicin (Dox). After accumulation in cancer cells, PDA generates cytotoxic heat upon excitation of NIR light for photothermal therapy. On the other hand, the temperature increment is able to destroy the template of AgNCs, leading to the fluorescence variation and controlled release of Dox for chemotherapy. The combined nanosystem exhibits outstanding fluorescence tracing, NIR photothermal transduction, as well as chemo drug delivery capabilities. Both in vitro and in vivo results demonstrate excellent tumor growth suppression phenomena and no apparent adverse effects. This research provides a powerful targeted nanoplatform for cancer theranostics, which may have great potential value for future clinical applications.
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Food & Function
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2021
·Vol. 12
·期 4
·1580-1589
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IF 5.396
Qian Zhou,Jia-Yi Yin,Wei-Yue Liang,Dong-Mei Chen,Qing Yuan,Bao-long Feng,Ying-Hua Zhang,Yu-Tang Wang
Gout is a common inflammatory arthritis associated with various comorbidities, such as cardiovascular disease and metabolic syndrome. Xanthine oxidase inhibitors (XOIs) have emerged as effective substances to control gout. Much attention has been given to the search for natural XOIs. In this study, a molecular database of natural XOIs was created for modeling purposes. Quantitative structure–activity relationship models were developed by combining various machine learning approaches and three descriptor pools. The models revealed several features of XOIs, including hydrophobicity and steric molecular structures. Experimental results showed the xanthine oxidase (XO) inhibitory activity of predicted compounds. Vanillic acid was identified as a promising new XOI candidate, with an IC50 of 0.593 μg mL−1. The functions of hydrogen bonds and hydrophobic interactions in XO activity inhibition were confirmed by molecular docking. This study fills knowledge gaps pertaining to the discovery of natural XOIs and to the interaction mechanisms between XOIs and XO.
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SCIENCE OF THE TOTAL ENVIRONMENT
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2020
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IF 6.551
Naiyi Yin,Zeliang Han,Huili Du,Pengfei Wang,Yunpeng Li,Xiaochen Chen,Guoxin Sun,Yanshan Cui,Zhengyi Hu
To determine the effect of vitamin supplements on the oral bioaccessibility of Pb in soils, Pb bioaccessibility was measured in the presence of 9 vitamins by a physiologically based extraction test. Gastric Pb bioaccessibility (G-BA, 2.6–83.3%) was found to be mostly reduced (1.1–3.1 fold) in the presence of B vitamins, specifically vitamins B1, B6, and B9. In contrast, a significant increase in Pb G-BA was observed with vitamin C and E involved. In the small intestinal phases, Pb bioaccessibility (I-BA) ranged from 0.1% to 16.0%, being 5–50 fold lower than the corresponding G-BA values. Vitamin C supplementation showed a 7-fold increase in Pb I-BA, with a similar increase presented in approximately 30% of samples treated to vitamin B involvement. Lead liberation in gastrointestinal digests was associated with the dissolution of Fe and Mn regulated by vitamins. In conclusion, the addition of B vitamins resulted in the reduction of gastric Pb bioaccessibility, but the bioaccessibility value increased in participation of vitamin C and E. Elevated intestinal bioaccessibility was found especially for vitamin C. This should contribute to more accurate assessment of health risks from contaminated soils. Nutritional management aimed at preventing Pb-induced toxicity can benefit from knowledge of vitamin influence on soil Pb bioaccessibility.
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Frontiers in Chemistry
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2020
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IF 3.693
Zheng Zhaojuan,Xu Qianqian,Tan Huanghong,Zhou Feng,Ouyang Jia
Upgrading of furanic aldehydes to their corresponding furancarboxylic acids has received considerable interest recently. Herein we reported selective oxidation of furfural (FAL) to furoic acid (FA) with quantitative yield using whole-cells of Pseudomonas putida KT2440. The biocatalytic capacity could be substantially promoted through adding 5-hydroxymethylfurfural into media at the middle exponential growth phase. The reaction pH and cell dosage had notable impacts on both FA titer and selectivity. Based on the validation of key factors for FAL conversion, the capacity of P. putida KT2440 to produce FAL was substantially improved. In batch bioconversion, 170 mM FA was produced with selectivity nearly 100% in 2 h, whereas 204 mM FA was produced with selectivity above 97% in 3 h in fed-batch bioconversion. Particularly, the role of molybdate transporter in oxidation of FAL and 5-hydroxymethylfurfural was demonstrated for the first time. The furancarboxylic acids synthesis was repressed markedly by destroying molybdate transporter, which implied Mo-dependent enzyme/molybdoenzyme played pivotal role in such oxidation reactions. This research further highlights the potential of P. putida KT2440 as next generation industrial workhorse and provides a novel understanding of molybdoenzyme in oxidation of furanic aldehydes.
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APPLIED CATALYSIS B-ENVIRONMENTAL
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2020
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IF 16.683
Wei Liu,Yusen Yang,Lifang Chen,Enze Xu,Jiaming Xu,Song Hong,Xin Zhang,Min Wei
Activation of oxygen-containing functional groups plays a key role in sustainable biomass upgrading and conversion. In this work, a NiMo intermetallic compound (IMC) catalyst was prepared based on layered double hydroxides (LDHs) precursors, which displayed prominent catalytic performance for furfural hydrodeoxygenation (HDO) to 2-methylfuran (2-MF) (yield: 99 %) at a rather low hydrogen pressure (0.1 MPa), significantly superior to NiMo alloy, monometallic Ni and other Ni-based catalysts ever reported. CO-IR, STEM, EXAFS and XANES give direct evidences that the atomically-ordered Ni/Mo sites in NiMo IMC determine the uniform bridging-type adsorption mode of C O bond in furfural whilst adsorption of furan ring is extremely suppressed. In situ FT-IR and DFT calculation further substantiate that ordered Ni-Mo bimetallic sites of IMC, in contrast to the random atomic sequence in NiMo alloy, facilitate the activation and cleavage of C OH bond in the intermediate (furfuryl alcohol, FOL), accounting for the production of 2-MF. This work demonstrates the decisive effect of atomically-ordered active sites in IMC catalyst on activation of oxygen-containing functional groups and product selectivity, which can be extended to catalytic upgrading of biomass-derived platform molecules.
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CHEMICAL ENGINEERING JOURNAL
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2020
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IF 10.652
Zhanlin Zhang,Hui Yan,Shang Li,Yuan Liu,Pan Ran,Weijia Chen,Xiaohong Li
The navigation of drug-loaded nanocarriers is confronted with series of physiological and pathological barriers in blood circulation, tissue penetration and cell internalization. In the current study, self-propelled micromotors of fiber rods are proposed to address the transportation barriers of chemotherapeutic drugs. Fiber rods with distinct Janus structure are prepared by side-by-side electrospinning, and urease and folate are conjugated on the respective sides of Janus rods (JRs) as power source and targeting ligands of Janus micromotors (JMs). The grafting density of urease determines the motion velocity and trajectory of JMs, and the high motion velocity and large mean-square displacement are detected in both phosphate-buffered saline and simulated extracellular matrices of tumor tissues. Despite no interference with the uptake pathway, the self-propelled motion promotes the folate-mediated cell internalization of JMs and maximizes the toxicities and apoptosis rate of tumor cells. The self-propulsion force from one side of JMs enhances the lateral drift and extravasation across blood vessel walls, increasing their accumulation in tumor tissues by around 2 folds and, doxorubicin accumulation, by around 2.6 folds. The treatment with JMs remarkably inhibits the tumor growth, prolongs the animal survival rate and induces strong tumor necrosis without obvious histopathological and hematological abnormalities to normal tissues. Thus, this study demonstrates a feasible strategy in combating the navigation barriers of blood vessel extravasation, tumor tissue diffusion and cell capture, effectively promoting the treatment efficacy and alleviating side effects of chemotherapeutic agents.
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Nanoscale
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2020
·Vol. 12
·期 41
·21234-21247
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IF 6.895
Jinjin Chen,Lulu Zhou,Chunhui Wang,Yunhao Sun,Yonglin Lu,Ruihao Li,Xiaochun Hu,Mengyao Chen,Lv Chen,Keke Chai,Tianming Yao,Shuo Shi,Chunyan Dong
A combination of chemotherapy and phototherapy has been proposed as a promising treatment for esophageal cancer (EC). Irinotecan as a first-line treatment option is widely prescribed for metastatic EC, however, its clinical application is extremely restricted by the low conversion rate to SN38, severe myelosuppression and diarrhea. As a more potent active metabolite of irinotecan, SN38 is a better substitution for irinotecan, but the poor water solubility and the difficulty of encapsulation hindered its medical application. Herein, a multifunctional SN38-conjugated nanosystem (FA-PDA@PZM/SN38@BSA-MnO2, denoted as FA-PPSM) is designed for overcoming the above-mentioned drawbacks and achieving collaborative chemotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT). The tumor acidic microenvironment induces decomposition of BSA-MnO2 nanoparticles into O2 and Mn2+, thus enhancing oxygen-dependent PDT efficacy; meanwhile, Mn2+ can be employed as a magnetic resonance imaging (MRI) contrast agent. Under 650 and 808 nm laser irradiation, the FA-PPSM nanocomposites exhibit superior antitumor efficacy in Eca-109-tumor bearing mice. Notably, there is low gastrointestinal toxicity and myelosuppression in the FA-PPSM treated mice compared with those treated with irinotecan (alone). Taken together, this work highlights the great potential of the FA-PPSM nanocomposites for MRI-guided chemotherapy in combination with endoscopic light therapy for esophageal cancer.
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Nano-Micro Letters
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2020
·Vol. 12
·期 1
·1-18
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IF 12.264
Li Yang,Lin Jinyan,Wang Peiyuan,Luo Qiang,Zhu Fukai,Zhang Yun,Hou Zhenqing,Liu Xiaolong,Liu Jingfeng
A pH/ROS cascade-responsive carrier-free nanodrug with self-targeting activation and ROS regeneration abilities.
On-demand release of VES in response to intracellular ROS to accelerate drug release via positive-feedback loop.
Highly synergistic therapeutic efficiency via orchestrated cooperation of oxidation-chemotherapy.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2020
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IF 4.389
Ping Tang,Meishuang Xing,Xinyue Xing,Qiao Tao,Wendai Cheng,Shengde Liu,Xiaoxu Lu,Liyun Zhong
Phototherapy, especially the photothermal therapy (PTT) and the photodynamic therapy (PDT), have become very promising in cancer treatment due to its low invasiveness and high efficacy. Both PTT and PDT involve the utilization of light energy, and their synergistic treatment should be a good solution for cancer treatment by ingenious design. The therapeutic effect of phototherapy is closely associated with the amount and location of anticancer-nanodrugs accumulated in tumor cells, and the receptor-mediated endocytosis should be an excellent candidate for enhancing anticancer-nanodrugs internalization. Surface enhanced Raman spectroscopy (SERS) imaging is suitable for tracing nanodrugs due to its high selectivity, sensitivity and reliability. In this paper, we hope to construct a receptor-mediated PTT/PDT synergistic anticancer nanodrugs and evaluate the corresponding efficacy through SERS tracing function. Here, the receptor-mediated PTT/PDT synergistic anticancer nanodrugs are prepared by the chemical modification of gold nanorods (GNRs), involving protoporphyrin IX (PpIX), 4-mecaptobenzoic acid (MBA), and folic acid (FA). The achieved results show that the receptor-mediated endocytosis can greatly facilitate the internalized amount and intracellular distribution of the nanodrugs, thus lead to the anti-cancer efficacy improvement. Importantly, this receptor-mediated PTT/PDT synergistic treatment with SERS tracing function will provide a simple and effective strategy for the design and application of anticancer phototherapy nanodrugs.
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Frontiers in Chemistry
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2020
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IF 3.693
Niu Weina,Wang Jianguo,Wang Qinyao,Shen Jianjun
Ovarian cancer is a gynecological cancer from which it is difficult to be completely cured. It is common to use regimens as an effective treatment for ovarian cancer, but these inevitably bring serious side effects. New treatment strategies and special drugs are needed to improve the prognosis of patients. Celastrol is a natural product, isolated from traditional medicine, that has been proven to be curative for inflammation and cancers. However, the non-targeting and low solubility of celastrol limit its clinical application. We prepared celastrol-loaded nanoparticles for the efficient treatment of ovarian cancer via oxidative stress amplification. In this work, a tumor-targeted, ROS-sensitive nanoparticle was designed, synthesized, and assembled into a drug delivery system that used celastrol. Folic acid (FA) groups on the surface of nanoparticles guide them to actively target the surface of the tumor cell membrane. Thioketal (TK) bonds in nanoparticles can be oxidized and broken into -SH within the ROS level of tumor tissues, which causes the breaking of the PEG hydrophilic shell layer of nanoparticles and promotes the release of celastrol. The released celastrol further stimulated the production of ROS and amplified the intracellular ROS level to promote the apoptosis of tumor cells, thus achieving a therapeutic effect on the celastrol treated ovarian cancer.
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