NEW JOURNAL OF CHEMISTRY
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2023
·
IF 3.3
Guili Ge,Hanyu Tu,Dan Wang,Mingjian Chen,Zhaoyang Zeng,Can Guo,Xu Wu,Wei Xiong
Fe-CDs-PEG, leading to the occurrence of excess iron, iron metabolism disorder, GSH consumption, reactive oxygen species (ROS) accumulation, and activated the ferroptosis pathway, can enhance radiotherapy sensitivity by inducing ferroptosis in lung cancer cells. This study provides a new idea for effective therapy of lung cancer.
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Pharmaceutics
·
2023
·Vol. 16
·期 1
·45
·
IF 5.4
Xiaowei Zhang,Rundong Zhu,Xingzhi Wang,Hao Wang,Zushun Xu,Yongan Wang,Dongqin Quan,Liao Shen
Local chemotherapy is an alternative therapeutic strategy that involves direct delivery of drugs to the tumor site. This approach avoids adverse reactions caused by the systemic distribution of drugs and enhances the tumor-suppressing effect by concentrating the drugs at the tumor site. Drug-loaded microspheres are injectable sustained-release drug carriers that are highly suitable for local chemotherapy. However, a complex preparation process is one of the main technical difficulties limiting the development of microsphere formulations. In this study, core-shell structured microspheres loaded with paclitaxel (PTX; with a core-shell structure, calcium alginate outer layer, and a poly (lactic acid-co-glycolic acid) copolymer inner layer, denoted as PTX-CA/PLGA-MS) were prepared using coaxial electrostatic spray technology and evaluated in vitro and in vivo. PTX-CA/PLGA-MS exhibited a two-stage drug release profile and enhanced anti-tumor effect in animal tumor models. Importantly, the preparation method reported in this study is simple and reduces the amount of organic solvent(s) used substantially.Keywords:chemotherapy;controlled drug-release;microspheres;electrostatic spray
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FOOD AND CHEMICAL TOXICOLOGY
·
2021
·
IF 6.025
Bangrong Cai,Mengya Liu,Jinxing Li,Dujuan Xu,Jiansheng Li
Chronic obstructive pulmonary disease (COPD) is widely recognized as a global public health problem and the third leading cause of mortality worldwide by 2020. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a dual-specificity protein and lipid phosphatase that plays an important role in COPD. However, the redox regulation of PTEN in the development of COPD was poorly studied. Our results showed that cigarette smoke extract (CSE) could oxidize PTEN in a time-dependent manner in BEAS-2B cells, whereas PTEN oxidation exposed to CSE was delayed compared to that of H 2 O 2. Additionally, we found that ROS derived from DUOX1 and 2 of NADPH oxidases were mainly responsible for oxidative inactivation PTEN, also simultaneously led to Trx-1 inactivation by dimerization . Oxidative mechanism of PTEN exposed to CSE was mediated by forming a disulfide bond between Cys 71 and Cys 124 , similar to H 2 O 2 . Inactivation of PTEN resulted in the increased phosphorylation of Akt. In conclusion, CSE exposure could elevate the intracellular ROS mainly from DUOX1 and 2 to oxidize PTEN and Trx-1 resulting in Akt activation, eventually cause the occurrence of COPD, suggesting that PTEN is a potential target for new therapies in COPD.
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RSC Advances
·
2021
·Vol. 11
·期 29
·17611-17621
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IF 3.361
Yanfei Liu,Shuo Long,Shanshan Zhang,Yifu Tan,Ting Wang,Yuwei Wu,Ting Jiang,Xiaoqin Liu,Dongming Peng,Zhenbao Liu
Although berberine (BBR) shows antioxidant activity, its activity is limited. We synthesized 9-O-benzoic acid berberine derivatives, and their antioxidant activities were screened via ABTS, DPPH, HOSC and FRAP assays. The para-position was modified with halogen elements on the benzoic acid ring, which led to an enhanced antioxidant activity and the substituent on the ortho-position was found to be better than the meta-position. Compounds 8p, 8c, 8d, 8i, 8j, 8l, and especially 8p showed significantly higher antioxidant activities, which could be attributed to the electronic donating groups. All the berberine derivatives possessed proper lipophilicities. In conclusion, compound 8p is a promising antioxidant candidate with remarkable elevated antioxidant activity and moderate lipophilicity.
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JOURNAL OF BIOMATERIALS APPLICATIONS
·
2021
·
IF 2.646
Qiang Li,Dongsheng Fu,Jie Zhang,Tianyang Li,Huifang Wang,Wenjuan Hou,Baolong Niu,Ruijie Guo,Yiming Liu
Encapsulation of therapeutic molecules into nanocarrier is an extensively explored strategy to treat cancer more effectively. In this study, pH-responsive targeting dual-agent delivery nanoparticles were prepared, into which hydrophilic doxorubicin hydrochloride (DOX) and hydrophobic curcumin (CUR) were entrapped. Tyrosine (Tyr) was grafted onto poly(aspartic acid) (PASP) to produce PASP-Tyr, the following reaction between hyaluronic acid (HA) and ethylenediamine (EDA) modified PASP-Tyr formed the nanocarrier HA-EDA-PASP-Tyr (HEPT), and the loading capacity was up to 50.9 ± 4.3% for CUR and 26.0 ± 1.9% for DOX. The spherical HEPT with the mean particle size of 142.9 ± 11.4 nm expanded and deformed into petaloid pattern with an increased size of about 2 µm when triggered by the acidic microenvironment. In vitro anticancer activity evaluation revealed that the co-loaded (DOX+CUR)@HEPT nanoparticles presented higher cytotoxicity against HCT-116 cells compared with that of the free combination of (DOX+CUR). Confocal laser scanning microscopy observation indicated that HEPT carrier promoted cellular uptake of drugs by means of active targeting capacity of HA ligand. With high loading capacity and tailored carrier structure, the nanoparticles formulations may offer a new strategy for cancer treatment.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2021
·
IF 5.268
Qiang Li,Dongsheng Fu,Jie Zhang,Hong Yan,Huifang Wang,Baolong Niu,Ruijie Guo,Yiming Liu
In this study, a new type of polypeptide, crosslinked methoxy poly(ethylene glycol)-g-poly(aspartic acid)-g-tyrosine (CPPT), was synthesized via a green and simple one-pot polymerization method. With the disulfide-crosslinked interlayer and the CaP shell, the pH and redox dual-sensitive polypeptide-based organic-inorganic hybrid nanoparticles encapsulated curcumin (Cur) into the hydrophobic core of micelles and loaded doxorubicin hydrochloride (DOX) on the hydrophilic segment of micelles as well as CaP shell. The spherical Cur- and DOX-loaded nanoparticles (CPPT@CaP-CD) showed a hydrodynamics size of about 157.9 ± 3.9 nm. The premature leakage of drugs from the nanoparticles at physiological pH was efficiently restrained because of the enhanced structure integrity, whereas at acidic and hypoxia microenvironment the release of both drugs was promoted due to the rapid dissolution of the CaP shell and the break of the disulfide crosslinked network, facilitating the stimuli-responsive controllable drugs release. In vitro anticancer activity evaluation revealed that the co-loaded nanoparticles presented higher cytotoxicity against A549 cells compared with that of the free combination of Cur + DOX. Confocal laser scanning microscopy observation indicated that more DOX and Cur were released into the nucleus triggered by the up-regulated intracellular glutathione (GSH) concentration and decreased pH, displaying enhanced cell uptake. The self-assembling polypeptide-based dual-sensitive drug co-delivery system could be a promising platform for efficient chemotherapy.
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Biomaterials Science
·
2021
·Vol. 9
·期 11
·4054-4065
·
IF 6.843
Desheng Cao,Hua He,Wei Li,Jin Yan,Jianhua Wu,Mengyuan Yin,Yang Zhou,Zhuchao Zhou,Lichen Yin
Anti-tumor treatment based on free radicals is often inefficient in hypoxic tumors, mainly because of the oxygen-dependent generation mechanism of reactive oxygen species (ROS). Herein, we report an NIR laser-controlled nano-system that is capable of generating alkyl radicals in situ in an oxygen-independent approach. Hollow mesoporous Prussian blue nanoparticles (HPB NPs) were developed to co-encapsulate the azo initiator (AIBI) and 1-tetradecanol as the phase change material (PCM, melting point of ∼39 °C), obtaining the AP@HPB NPs. At normal body temperature, the PCM remained in the solid state to prevent the pre-leakage of AIBI. Upon NIR laser irradiation (808 nm) at the tumor site, AP@HPB NPs generated heat upon photothermal conversion, which melted the PCM to release AIBI and decomposed AIBI to produce toxicity free alkyl radicals under both normoxic and hypoxic conditions. The alkyl free radicals efficiently killed tumor cells by causing oxidative stress and damaging DNA. Meanwhile, NIR light-induced hyperthermia cooperated with free radicals to efficiently eradicate tumors. This study therefore provides a promising strategy toward oxygen-independent free radical therapy, especially for the treatment of hypoxic tumors.
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CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Wenjia Wang,Xiaoqin Zhang,Zhiqian Li,Dayi Pan,Hongyan Zhu,Zhongwei Gu,Jie Chen,Hu Zhang,Qiyong Gong,Kui Luo
To achieve target delivery of anti-tumor drugs with great biocompatibility into tumor tissues, a stimuli-responsive dendronized hyaluronic acid (HA)-docetaxel conjugate (HA-DTX-Dendron, HADD) was designed and prepared. The incorporation of HA in HADD improved the delivery of DTX to tumor cells with rich CD44 receptors. Enhanced biocompatibility and therapeutic outcomes were achieved using glyodendrons-modified HA and tumor microenvironment-responsive linkers in HADD. The glycodendron was connected with HA via GSH-responsive disulfide bonds , and the drug DTX was linked to the carrier via a cathepsin B-responsive tetrapeptide GFLG. This design resulted in self-assembly nanostructures for facilitating uptake of HADD by tumor cells and rapid release of DTX to exert its therapeutic effect. Compared to free DTX, HADD showed much higher tumor growth inhibition in the MDA-MB-231 tumor-bearing mice model (up to 99.71%), and no toxicity was observed. Therefore, HADD could be employed as an efficacious nano-agent for treating triple negative breast cancer (TNBC).
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MICROCHEMICAL JOURNAL
·
2021
·
IF 4.821
Chunhe Yu,Dongmiao Qin,Xiaohua Jiang,Xiangfei Zheng,Biyang Deng
In this work, bright yellow fluorescent nitrogen-doped carbon quantum dots (YN-CQDs) are produced by a facile, inexpensive and eco-friendly hydrothermal technique using extract of chlorophyll from lettuce leaf as precursor. The quantum yield (QY) of as-synthesized YN-CQDs was up to 38%, which was higher than the previously reported quantum yield of most CQDs prepared using other biomass. Silver ion (Ag + ) can covalently bond with carboxyl, hydroxyl and amino groups on the surface of YN-CQDs and quench the fluorescence of YN-CQDs through static quenching. Upon addition of methimazole (MZ) to the YN-CQDs/Ag + dispersion system, Ag + releases from the YN-CQDs/Ag + complex due to the high affinity of MZ for Ag + and the quenched fluorescence of the YN-CQDs was recovered. Hence, we developed an off–on sensing method for the detection of MZ using YN-CQDs/Ag + as a fluorescent probe. Under optimal conditions, with addition of MZ, the fluorescence recovery of YN-CQDs/Ag + system happens with a good linearity in the range of 0.003 ~ 60 μmol/L and a detection limit of 0.8 nmol/L. The YN-CQDs/Ag + system exhibited good MZ determination performance. The established off–on fluorescence sensing platform was successfully employed for detecting MZ in mouse plasma.
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MOLECULES
·
2021
·Vol. 26
·期 14
·4300
·
IF 4.412
Lin Yang,Yangping Liu,Wenhui Zhang,Yujie Hua,Ban Chen,Quanzhou Wu,Dongfeng Chen,Shuqin Liu,Xican Li
The search for a safe and effective inhibitor of ferroptosis, a recently described cell death pathway, has attracted increasing interest from scientists. Two hydrolyzable tannins, chebulagic acid and chebulinic acid, were selected for the study. Their optimized conformations were calculated using computational chemistry at the B3LYP-D3(BJ)/6-31G and B3LYP-D3(BJ)/6-311 + G(d,p) levels. The results suggested that (1) chebulagic acid presented a chair conformation, while chebulinic acid presented a skew-boat conformation; (2) the formation of chebulagic acid requires 762.1729 kcal/mol more molecular energy than chebulinic acid; and (3) the 3,6-HHDP (hexahydroxydiphenoyl) moiety was shown to be in an (R)- absolute stereoconfiguration. Subsequently, the ferroptosis inhibition of both tannins was determined using a erastin-treated bone marrow-derived mesenchymal stem cells (bmMSCs) model and compared to that of ferrostatin-1 (Fer-1). The relative inhibitory levels decreased in the following order: Fer-1 > chebulagic acid > chebulinic acid, as also revealed by the in vitro antioxidant assays. The UHPLC–ESI-Q-TOF-MS analysis suggested that, when treated with 16-(2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinyloxy free radicals, Fer-1 generated dimeric products, whereas the two acids did not. In conclusion, two hydrolyzable tannins, chebulagic acid and chebulinic acid, can act as natural ferroptosis inhibitors. Their ferroptosis inhibition is mediated by regular antioxidant pathways (ROS scavenging and iron chelation), rather than the redox-based catalytic recycling pathway exhibited by Fer-1. Through antioxidant pathways, the HHDP moiety in chebulagic acid enables ferroptosis-inhibitory action of hydrolyzable tannins.Keywords:ferroptosis-inhibition;ferrostatin-1;chebulagic acid;chebulinic acid;hydrolyzable tannin;HHDP
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ANALYST
·
2021
·Vol. 146
·期 16
·5115-5123
·
IF 4.616
Haiyang Yao,Difei Jiang,Gaoqiu Dong,Jiamin Sun,Shasha Sun,Lingling Li,Fenfen Zheng,Weiwei Xiong
Dynamically monitoring intracellular glutathione (GSH), a crucial biomarker of oxidative stress, is of significance for the diagnosis and treatment of certain diseases. Although manganese dioxide (MnO2) based GSH fluorescent sensors have exhibited high sensitivity and good selectivity owing to the specific reactivity between GSH and MnO2, near-infrared (NIR) MnO2 based nanoprobes for GSH detection are scarce. Herein, we have developed a NIR activatable fluorescence nanoprobe for the imaging and determination of intracellular GSH based on a core–shell nanoparticle, consisting of NIR emitted gold nanocluster doped silica as the fluorescent core and manganese dioxide as the GSH-responsive shell (named AuNCs@MnO2). Due to the absorption competition mechanism, the outer MnO2 shell rather than the inner AuNCs core preferentially absorbed the excitation light, thus leading to fluorescence quenching of the inner AuNCs core. Upon addition of GSH, the fluorescence of the nanoprobe restored along with the reduction of MnO2 to Mn2+ because of the absorption competition disappearance-induced emission. The activatable fluorescence linearly increased upon changing the GSH concentration in the range of 2 to 5000 μM with a detection limit of 0.67 μM. The cytotoxicity test shows that the AuNCs@MnO2 nanoprobes have a good biocompatibility. After entering the cancer cells, the intracellular GSH degraded the outermost MnO2 shell and initiated the NIR fluorescence restoration of AuNCs, which can be used to monitor the dynamic change of intracellular GSH. This strategy provides an NIR-activatable way to detect GSH levels in living cells and offers a promising platform for the diagnosis and treatment of GSH-related diseases.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2021
·
IF 4.539
Shuhua Chang,Dawei Qin,Lizhen Wang,Mengli Zhang,Rongjun Yan,Cuiyun Zhao
The purpose of our research is to find a new nanoparticle to conjugate BSA with a low water-soluble antitumor compound, cinnamaldehyde (CA). In this study, a cinnamaldehyde derivative (CAH) was synthesized by reacting CA with anthraniloyl hydrazine (AH) to obtain a pharmaceutical carrier with medicinal activity, and the yield can be 95%. BSA–CAH nanoparticles (NPs) were prepared by a desolvation method. Following modification, the isoelectric point of the NPs increased to 5.5–6.0, with negative changes in tumor micro environment. The microscopy analyses revealed that the NPs were homogeneously dispersed and exhibited a circular-granular structure, with 172 nm size. The modified BSA was characterized for the structure by various spectral analysis. The results showed that the content of β-turns and the antiparallel β-sheet increased, the fluorescence intensity at 370 nm was also significantly enhanced and red-shifted, so that the degree of conjugation increased after modification. Gel permeation chromatography (GPC) revealed that the molecular weight of the NPs was 83.629 kDa, confirming that 56 CAH molecules were conjugated to one molecule of BSA. By stability analysis, in solution, the NPs were stable for 30 days at room temperature , comparing with free CA. Moreover, the cell uptake experiment revealed that BSA–CAH NPs entered cancer cells as carriers and inhibited the majority of the studied cancer cell lines by FITC label. Notably, the laryngeal cancer inhibition rate was >80%. BSA–CAH NPs prepared herein exhibited promising anticancer activity.
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