EUROPEAN JOURNAL OF PHARMACOLOGY
·
2022
·
IF 5.195
Hongyu Zhou,Yang Zhang,Yuan Tian,Yushi Sun,Yajuan Chen,Yanli Zhang,Qin Zhu,Junfang Pan,Chen Qing
9-nitrocamptothecin (9-NC), an active derivative of camptothecin (CPT), demonstrated antitumor effect on experimental tumors in mice by topoisomerase I (Topo I) inhibition. However, under human physiological conditions, the rapid opening of lactone ring of 9-NC resulting in the formation of inactive and high toxic carboxylate limited its clinical efficacy. Therefore, strategies aimed to maintain the active closed-lactone form of 9-NC in the plasma were developed, such as prodrugs . In our study, 9-nitro-20(S)-carbonate-camptothecin (NCP4), a novel prodrug of 9-NC, was designed and synthesized. A preclinical evaluation of the chemotherapeutic potential of NCP4 was performed in vitro and in vivo . In cytotoxicity assay against six human cancer cells, the cytotoxic effect of NCP4 was slightly weaker than 9-NC. In addition, our data showed that 9-NC can be converted from NCP4 in vivo , and that the intracellular conversion of NCP4 to its active metabolites was correlated well with its cytotoxicity, demonstrating that NCP4 could serve as a prodrug of 9-NC. In human hepatoma Bel-7402 xenografts, NCP4 by intravenous injection showed more potent antitumor efficacy than 9-NC. Mechanistically, NCP4 induced cell apoptosis by increasing the expressions of caspase-3 and Bax in tumor tissues. In human hepatoma Hep G2 xenografts, NCP4 by oral administration significantly inhibited tumor growth. Importantly, the toxic effect of NCP4 on mice was much lower than 9-NC, demonstrating improved safety of NCP4. Overall, our study indicated that NCP4 would be a promising anticancer candidate and worthy of further investigation.
研究领域:
肿瘤学
·
药理学
·
分子生物学
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DOI
PubMed
高影响因子
CERAMICS INTERNATIONAL
·
2023
·
IF 5.2
Hailong Pan,Shijie Yan,Yiyun Zhang,Jialun Du,Xiaoyu Zhang,Pijun Gong,Haitao Wu,Huanrong Tian,Michael Wübbenhorst
A series of Ce 2 [Zr 1- x (A) x ] 3 (MoO 4 ) 9 (A = Sr 1/3 Ta 2/3 , Sr 1/3 Sb 2/3 ; x = 0.02, 0.04, 0.06, 0.08 and 0.10) (abbreviated as CZ 1- x T x and CZ 1- x S x ) microwave dielectric ceramics were studied systematically with respect to microstructures, sintering behaviors, crystal structures, microwave dielectric properties and infrared vibrational modes. Density measurements and scanning electron microscopy (SEM) reveal the dense and homogeneous microstructures. X-ray diffraction (XRD) results confirm the formation of solid solutions belonging to the hexagonal system with a R 3 ‾ c space group, and the lattice volume increases with raising the doping content. Furthermore, the complex chemical bond theory was used to calculate the intrinsic bond parameters, and the correlations between the microwave dielectric properties and intrinsic bond parameters were established. Finally, far infrared (FIR) spectra reveal that the main polarization contribution stems from the absorptions of the phonon oscillations in these two groups of ceramics. Typically, the optimum microwave dielectric properties are achieved for CZ 0.9 T 0.1 and CZ 0.94 S 0.06 ceramics with ε r = 10.24, Q × f = 92,009 GHz (at 9.70 GHz), τ f = −8.84 ppm °C −1 and ε r = 10.40, Q × f = 82,696 GHz (at 9.69 GHz) and τ f = −8.04 ppm °C −1 , respectively. Interestingly, the CZ 0.9 T 0.1 ceramic exhibits the maximum Q × f value in the ion doped Ce 2 Zr 3 (MoO 4 ) 9 ceramics while retaining a good τ f = −8.84 ppm °C −1 .
研究领域:
材料科学
·
陶瓷
·
介电材料
·
固体化学
·
微波工程
✓ 已验证
DOI
高影响因子
Nanoscale
·
2020
·Vol. 12
·期 9
·5380-5396
·
IF 6.895
Yalin Sun,Yan Liang,Na Hao,Xiaoheng Fu,Bin He,Shangcong Han,Jie Cao,Qingming Ma,Wen Xu,Yong Sun
9-Nitro-20(S)-camptothecin (9-NC) is a broad-spectrum antitumor drug used in tumor treatments, but its clinical applications and antitumor efficacy are limited by its structural instability, poor solubility, and extremely low drug utilization in tumor tissues. In this study, enzyme-sensitive nuclear-targeted dual-functional polymeric micelles were developed for 9-NC delivery with a high drug loading content (12.93 ± 0.88%), steady-state circulation, and a rapid attack at the “heart” of tumor cells. Briefly, chrysin (CHR) as a π-conjugated moiety was immobilized on the PCL terminal in the TAT–PCL amphiphiles and combined with the ALAL peptide as a linker on HA chains to yield the ultimate CHR–PCL–TAT–ALAL–HA (HATPC) amphiphiles. Spherical 9-NC-loaded micelles were obtained from the self-assembly of the dual-functional amphiphiles comprising HATPC and 9-NC with uniform nanosize (121.6 ± 5.79 nm), well-distributed morphology (PDI: 0.256), and negative surface charge (−23.2 ± 0.5 mV), yielding high stability during blood circulation. In this drug delivery system, HA acts as an active tumor-targeting instrument via CD44-receptor-mediated endocytosis; further, the ALAL peptide could be cutoff in the lysosomes of the tumor cells due to the high expression of cathepsin B, leading to lysosomal escape, while the secondary polymeric micelles targeted the tumor cell nucleus via the exposed TAT peptide. The enzyme sensitivity and nuclei targetability of the 9-NC/HATPC micelles were confirmed by dynamic light scattering and confocal laser scanning microscopy analyses. As compared to free 9-NC and traditional mPEG2k–PCL2k polymeric micelles, 9-NC/HATPC micelles were the most concentrated in the tumor cell nucleus; therefore, they exhibited the highest cytotoxicity against SKOV3 tumor cells both in vitro (IC50 = 0.03 μg mL−1) and in vivo. This enzyme-sensitive nuclear-targeted dual-functional drug delivery system involving HATPC provided a new and promising strategy for enhanced 9-NC delivery and antitumor efficacy.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Shiji Fang,Liyun Zheng,Gao-Feng Shu,Chen Xiaoxiao,Xiaoju Guo,Yiming Ding,Wenjing Yang,Jiale Chen,Zhongwei Zhao,Jianfei Tu,Minjiang Chen,Jian-Song Ji
Immunotherapy is the most promising systemic therapy for hepatocellular carcinoma. However, the outcome remains poor. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a role in altering cell-surface protein levels, potentially undermining the efficacy of immunotherapy against tumors. This highlights its potential as a target for antitumor therapy. Herein, CaCO3-based nanoparticles coencapsulated with DOX, an immunogenic cell death (ICD) inducer, and evolocumab was developed to enhanced the efficacy of immunotherapy. The obtained DOX/evolocumab-loaded CaCO3 nanoparticle (named DECP) exhibits a good capacity of acid neutralization and causes ICD of cancer cells. In addition, DECP is able to evaluate the cell-surface level of MHC-I, a biomarker that correlates positively with patients’ overall survival. Upon intravenous injection, DECP accumulates within the tumor site, leading to growth inhibition of hepa1-6 bearing subcutaneous tumors. Specifically, DECP treatment causes augmented ratios of matured dendritic cells, tumor-infiltrating CD8+ T cells and natural killing cells, while concurrently depleting Foxp3+ regulatory T cells. Peritumoral delivery of DECP enhances the immune response of distant tumors and exhibits antitumor effects when combined with intravenous αPD-L1 therapy in a bilateral tumor model. This study presents CaCO3-based nanoparticles with multiple immunomodulatory strategies against hepatocellular carcinoma by targeting PCSK9 inhibition and modulating immune homeostasis in the unfavorable TME.
研究领域:
肿瘤学
·
免疫学
·
纳米技术
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
·
2022
·Vol. 2022
·期 21
·e202200176
·
IF 2.551
Guanyu Ma,Yun Tang,Leyi Chen,Lubing Qin,Quanli Shen,Likai Wang,Zhenghua Tang
Graphical We report a novel homoleptic alkynyl-protected Au(I)9-Ag(I)9 cluster, which features an intriguing ichthyomorphic assembled core structure. It shows distinct absorbance feature and luminescence properties in solution and in the solid state. Interestingly, it has excellent catalytic performance in both the hydrogen evolution reaction and the reduction of 4-nitrophenol. We report the structure analysis, optical property, and catalytic implications of homoleptic alkynyl-protected Au(I)-Ag(I) nanocluster, namely Au 9 Ag 9 (C≡CAr F ) 18 (abbreviated as Au9 Ag9 hereafter). Single crystal X-ray diffraction analysis disclosed that, the core of Au 9 Ag 9 cluster features intriguing ichthyomorphic assembled structure driven by metallophilic interactions and Au-acetylide linkages. The Au 9 Ag 9 nanocluster is fluorescent in both solution and solid state, and it has much higher quantum yield in solid state. In the electrochemical hydrogen evolution reaction (HER) test, Au 9 Ag 9 nanocluster exhibits a favorable overpotential of 274 mV at 10 mA cm −2 with a Tafel slope of 99 mV dec −1 , which markedly surpass than the [Au(C≡C-Ar F )] f and [Ag(C≡C-Ar F )] f control samples. Furthermore, Au 9 Ag 9 nanocluster shows much higher activity than the other two to catalyze the reduction of 4-nitrophenol.
✓ 已验证
产品关联
DOI
高影响因子
NEUROCHEMICAL RESEARCH
·
2016
·Vol. 41
·期 8
·2110-2118
·
IF 2.472
Zhu Mingming,Li Bingfei,Ma Xiao,Huang Cong,Wu Rui,Zhu Weiwei,Li Xiaoting,Liang Zhaofeng,Deng Feifei,Zhu Jianyun,Xie Wei,Yang Xue,Jiang Ye,Wang Shijia,Wu Jieshu,Geng Shanshan,Xie Chunfeng,Zhong Caiyun,Liu Haiyan
Aluminum (Al)-induced apoptosis is considered as the major cause of its neurotoxicity. Folic acid possesses neuroprotective function by preventing neural cell apoptosis. microRNAs (miRNAs) are important regulators of gene expression participating in cellular processes. As a key component of the miR-17-92 cluster, miR-19 is implicated in regulating apoptotic process, while its role in the neuroprotective effect of folic acid has not been investigated. The present study aimed to investigate the potential involvement and function of miR-19 in the protective action of folic acid against Al-induced neural cell apoptosis. Human SH-SY5Y cells were treated with Al-maltolate (Al-malt) in the presence or absence of folic acid. Results showed that Al-malt-induced apoptosis of SH-SY5Y cells was effectively prevented by folic acid. Al-malt suppressed the expression of miR-19a/19b, along with alterations of miR-19 related apoptotic proteins including PTEN, p-AKT, p53, Bax, Bcl-2, caspase 9 and caspase 3; and these effects were ameliorated by folic acid. miR-19 inhibitor alone induced apoptosis of SH-SY5Y cells. Combination treatment of folic acid and miR-19 inhibitor diminished the neuroprotective effect of folic acid. These findings demonstrated that folic acid protected neuronal cells against Al-malt-induced apoptosis by preventing the downregulation of miR-19 and modulation of miR-19 related downstream PTEN/AKT/p53 pathway.
研究领域:
神经科学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2019
·Vol. 37
·期 7
·664-673
·
IF 2.804
Liu Ya-Di,Zhang Qiang,Yu Xin-Hong,Liu Jian-Gang,Han Yan-Chun
For poly(9,9-dioctylfuorene) (PFO), β phase (coplanar conformation with the intra-chain torsion angle of 165°) has a greater conjugation length and higher degree of order compared to those of α phase, which favors charge carrier transport. However, the highest content of β phase obtained so far is 45%. We propose to increase the content of β phase by promoting the solution aggregation of PFO molecules and extending film-forming time. For this purpose, 1,8-diiodooctane (DIO) is added to PFO o -xylene solution, which enhances the interaction of PFO chains and improves the planarity of PFO backbone, resulting in the formation of ordered aggregation. The aggregates act as nucleation centers to promote the formation of β phase. The content of β phase increases with increasing DIO concentration and reaches a platform of 39% as DIO is more than 4 vol%. Furthermore, the film is kept in a sealed environment with o -xylene atmosphere for 3 h, thus the PFO molecules have enough time to diffuse to the crystallization front and achieve disorder-order transition. As a result, the crystallinity of PFO is improved significantly and the content of β phase increases to 52%, reaching the highest value reported so far.
研究领域:
高分子化学
·
材料科学
·
凝聚态物理
·
纳米技术
·
光电材料
·
有机电子学
✓ 已验证
DOI
高影响因子
JOURNAL OF MEMBRANE SCIENCE
·
2022
·
IF 10.53
Yirong Sun,Jundong Zhong,Ziyu Lin,Ruiyin Sun,Liyuan Chen,Zhenhua Jiang,Jinhui Pang
Interfacial polymerization has always been a research hotspot for the preparation of polyamide (PA) membranes for molecular sieving. In previous reports, water-soluble amines (such as piperazine (PIP), m-phenylenediamine (MPD), etc.) were mostly used as monomers containing amino functional groups in the aqueous phase to conduct interfacial polymerization with 1,3,5-mesotribenzoyl chloride (TMC) in hexane , resulting in a dense PA film. However, this approach limits the diversity of polymer structures in PA films. To introduce water-insoluble 9,9-Bis(4-aminophenyl)fluorene (BAF) with a rigid twisted structure into interfacial polymerization, this study reports the interfacial polymerization of BAF in DMF/water solution with TMC in n-hexane. BAF-PA films with a larger free volume compared with MPD-PA were successfully prepared. The anomalous interfacial diffusion phenomenon was explained by the interfacial properties and molecular diffusion mechanism of the two-phase solvent and was confirmed by observing the microscopic morphology of the film. Since the structure of BAF-PA has a larger free volume, the BAF-PA film prepared by co-solvent interfacial polymerization has higher permeance to methanol (23.88 L m −2 h −1 bar −1 ). Meanwhile, it has more than 90% rejection of dyes with molecular weights of 585 Da and above. The large free volume PA film prepared with DMF/water mixed solvent exhibited excellent performance in organic solvent nanofiltration . This method also offers the possibility of introducing other water-insoluble amines into the interfacial polymerization to prepare PA films.
研究领域:
材料科学
·
化学工程
✓ 已验证
产品关联
DOI
高影响因子
POLYMER
·
2012
·
IF 3.438
Changwei Huang,Nianfa Yang,Anlin Zhang,Liwen Yang
Optically active helical poly[( R or S )-3-(9-alkylfluoren-9-yl)propene oxide]s (poly-AFPOs) were used to induce the enantioselective addition of methyllithium to aldehydes. The addition of methyllithium to 4-methoxybenzaldehyde gave the highest enantioselectivity (88% ee) under the inducement of poly-AFPOs. Poly-AFPOs could be recovered simply by pouring the reaction mixture into methanol in the end of the reaction and separating the precipitated polymer via filtration. The recovered poly-AFPOs could be reused for many times to induce the enantioselective addition of methyllithium to aldehyde without losing their enantioselective inducement ability. The investigation of the optical rotation and the MALDI-ToF MS confirmed that, in the enantioselective addition induced by poly-AFPOs, the lithium cation was embedded in the hole of the helical column of poly-AFPOs, leaving the negative methyl ion outside the one-handed helical column. The methyl anion abutted tightly against the helical polymer and acquired a chiral environment. It was this helically chiral environment that resulted in the enantioselective inducement of the addition reaction.
研究领域:
有机化学
·
高分子化学
✓ 已验证
产品关联
DOI
高影响因子
Food & Function
·
2026
·
IF 6.3
Yang Liu,Xin Zhang,Jiaying Yu,Wangge Xiong,Yaqi Li,Jinsheng Zhang,Jing Guo
This study utilized scanning electron microscopy (SEM), enzymatic kinetics, multispectral analysis, and molecular simulations to explore the effects of theaflavins (TFs) on Streptococcus mutans (S. mutans) biofilms and matrix metalloproteinase-9 (MMP-9) and the TF–MMP-9 interaction mechanism. The results demonstrated that TFs can disrupt the biofilms of S. mutans and reversibly and competitively inhibit MMP-9. TFs can spontaneously bind to MMP-9, with hydrogen bonds being the primary driving forces. Furthermore, fluorescence spectroscopy revealed that the fluorescence quenching mechanism of TFs on MMP-9 is static quenching, and this interaction alters the microenvironmental characteristics of tyrosine and tryptophan residues within MMP-9. Importantly, TFs induce a transformation of the secondary structure of MMP-9 into a more ordered and compact conformation. Interestingly, the inhibitory activity followed the order: theaflavin (TF1) < theaflavin-3-gallate (TF2A) ≈ theaflavin-3′-gallate (TF2B) < theaflavin-3,3′-digallate (TF3), suggesting that the number of galloyl groups positively correlates with the inhibitory effect. These findings indicate that TFs have great potential for application in preventing and slowing down the progression of dental caries.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2022
·Vol. 46
·期 36
·17374-17385
·
IF 3.925
Sidra Mushtaq,Shuai Bi,Fan Zhang,Muhammad Moazzam Naseer
Conjugated microporous polymers (CMPs) are highly desirable materials with larger surface areas, open channels, and semiconducting properties, which enable them to remove various hazardous pollutants from wastewater via adsorption or photocatalytic degradation. This study reports a novel monomer 9,9′-bifluorenylidene (9,9′-BF) as a versatile building block for the synthesis of CMPs via Yamamoto and Suzuki polymerization. The synthesized CMP-P1 and CMP-P2 with fully unsaturated π-conjugated backbones showed strong visible-light absorption, semiconducting nature, and high porosities. These fascinating properties allow these polymers to efficiently catalyze dye degradation under visible light. The photocatalytic results of both CMP-P1 and CMP-P2 showed a higher degradation efficiency for methylene blue (MB), rhodamine B (RhB), and methyl orange (MO), even better than those of most of the reported polymer photocatalysts. The higher photocatalytic degradation ability of CMP-P1 as compared to CMP-P2 might be due to a higher apparent surface area of 1257 m2 g−1 and a narrower bandgap (1.74 eV). Most importantly, these CMPs selectively degraded MB in the mixtures of MB + RhB and MB + MO. The photocatalytic mechanism study indicated the involvement of oxygen and electrons as the main reactive species in the degradation process. The excellent photodegradation results of these new photocatalysts indicate their high potential in water purification applications.
研究领域:
材料科学
·
环境科学
✓ 已验证
DOI
高影响因子
Polymer Chemistry
·
2022
·Vol. 13
·期 23
·3506-3512
·
IF 5.364
Yuanzuo Zou,Dan Wang,Jingzhou Guo,Junwei Yang,Yuan Pu,Jian-Feng Chen
One of the most suitable methods for synthesizing conjugated polymers is the Suzuki cross-coupling reaction because of its high tolerance and stability. Herein, we report an improved strategy to synthesize conjugated polymers via Suzuki cross-coupling polymerization in a rotating packed bed (RPB) reactor. The synthesis of poly(9,9-dioctylfluorene) (PFO) was systematically investigated. The enhancement of mixing and mass transfer from the RPB ensured the uniformity of the contact probability of active functional groups and the consistency of the growth rate of molecular chains. Therefore, under the optimized experimental parameter of 2.0 mmol monomer equivalents, the polydispersity index (PDI) of the PFO synthesized in the RPB was maintained at about 2.0, which was much lower than that of the traditional synthesis method in stirred reactors. Further, the performance of polymer light-emitting diodes prepared using PFO with a low PDI was more stable.
研究领域:
材料科学
·
化学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）