International Journal of Nanomedicine
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2020
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IF 5.115
Yan Liang,Jing Zhang,Baocheng Tian,Zimei Wu,Darren Svirskis,Jingtian Han
Aim Sequential treatment with paclitaxel (PTXL) and gemcitabine (GEM) is considered clinically beneficial for non-small-cell lung cancer. This study aimed to investigate the effectiveness of a nano-system capable of sequential release of PTXL and GEM within cancer cells.Methods PTXL-ss-poly(6-O-methacryloyl-d-galactopyranose)-GEM (PTXL-ss-PMAGP-GEM) was designed by conjugating PMAGP with PTXL via disulfide bonds (-ss-), while GEM via succinic anhydride (PTXL:GEM=1:3). An amphiphilic block copolymer N-acetyl-d-glucosamine(NAG)-poly(styrene-alt-maleic anhydride)58-b-polystyrene130 acted as a targeting moiety and emulsifier in formation of nanostructures (NLCs).Results The PTXL-ss-PMAGP-GEM/NAG NLCs (119.6 nm) provided a sequential in vitro release of, first PTXL (redox-triggered), then GEM (pH-triggered). The redox- and pH-sensitive NLCs readily distributed homogenously in the cytoplasm. NAG augmented the uptake of NLCs by the cancer cells and tumor accumulation. PTXL-ss-PMAGP-GEM/NAG NLCs exhibited synergistic cytotoxicity in vitro and strongest antitumor effects in tumor-bearing mice compared to NLCs lacking pH/redox sensitivities or free drug combination.Conclusion This study demonstrated the abilities of PTXL-ss-PMAGP-GEM/NAG NLCs to achieve synergistic antitumor effect by targeted intracellularly sequential drug release.
研究领域:
肿瘤学
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药剂学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
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IF 6.2
Xi Zhou,Qi Chu,Xin Zhang,Feifei Chen,Kequan Chen,Alei Zhang
In this study, a semirational design strategy integrating sequence and structural analyses was utilized to improve the thermostability of the highly active chitinase Chi1. Comprehensive screening for thermostability and enzymatic activity led to the identification of a beneficial mutant, D615S. Thermostability evaluations demonstrated that the half-life of the D615S mutant at 40 and 45 °C was prolonged by 3.6-fold and 24-fold, respectively, compared to that of the wild-type (WT) enzyme, while its melting temperature (Tm) was increased by 6.0 °C. Molecular dynamics (MD) simulations demonstrated that the D615S mutant significantly reduced local structural fluctuations and improved overall structural stability compared to the WT enzyme, leading to a remarkable enhancement in thermostability. Furthermore, the D615S mutant sustained the efficient enzymatic degradation of chitin powder via an integrated affinity adsorption-enzymatic catalysis approach, achieving a degradation rate of 50.3% within 120 h. Subsequent separation and purification processes yielded N-acetylglucosamine (NAG) and its dimer (NAG2) with purities exceeding 95%. These findings underscore the potential of the D615S mutant for industrial applications, particularly in the field of chitin degradation.
研究领域:
酶工程
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蛋白质稳定性
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结构生物学
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工业生物技术
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碳水化合物代谢
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2022
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IF 6.51
Yan Liang,Ping-Yu Wang,You-Jie Li,Ze-Yun Liu,Ran-Ran Wang,Guang-Bin Sun,Hong-Fang Sun,Shu-Yang Xie
Reduced drug uptake and elevated drug efflux are two major mechanisms in cancer multidrug resistance (MDR). In the present study, a new multistage O 2 -producing liposome with NAG/R8-dual-ligand and stimuli-responsive dePEGylation was developed to address the abovementioned issues simultaneously. The designed C-NAG-R8-PTXL/MnO 2 -lip could also achieve magnetic resonance imaging (MRI)-guided synergistic chemodynamic/chemotherapy (CDT/CT). In vitro and in vivo studies showed that C-NAG-R8-PTXL/MnO 2 -lip enhanced circulation time by PEG and targeted the tumor site. After tumor accumulation, endogenous l -cysteine was administered, and the PEG-attached disulfide bond was broken, resulting in the dissociation of PEG shells. The previously hidden positively charged R8 by different lengths of PEG chains was exposed and mediated efficient internalization. In addition, the oxygen (O 2 ) generated by C-NAG-R8-PTXL/MnO 2 -lip relieved the hypoxic environment within the tumor, thus reducing the efflux of chemotherapeutic drug. O 2 was able to burst liposomes and triggered the release of PTXL . The toxic hydroxyl radical (·OH), which was produced by H 2 O 2 and Mn 2+ , strengthened CDT/CT. C-NAG-R8-PTXL/MnO 2 -lip was also used as MRI contrast agent , which blazed the trail to rationally design theranostic agents for tumor imaging.
研究领域:
药学
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生物医学工程
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癌症研究
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Alei Zhang,Runke Wang,Xi Zhou,Quanzhen Liu,Xin Zhang,Feifei Chen,Kequan Chen
In this work, a GH18 chitinase (Chi1) with highly hydrolytic activity was identified from Chitinibacter sp. GC72 and successfully cloned and expressed in Escherichia coli BL21(DE3). The recombinant Chi1 exhibited specific activities of 362.6 U/mg against colloidal chitin and 56.7 U/mg against raw α-chitin. Analysis of hydrolysis pattern showed that Chi1 is a multifunctional chitinase, which mainly exhibited processive exo-acting activity with some endo-acting and N -acetyl glucosaminidase activities. Structural analysis and molecular docking were conducted to explore the potential mechanism underlying the highly and multiple activities. Furthermore, Chi1 was utilized to convert raw α-chitin into reducing sugar affording 48.6% ( w / w ) yield of total sugar with a 1:4 molar ratio of NAG to NAG 2 , while also displaying hydrolysis activity to chitinous biomass with 4.1% sugar yield. This study provides a potent chitinase to hydrolyze chitinous resource with unusual product pattern, showing great potential for further industrial applications.
研究领域:
微生物学
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分子生物学
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生物技术
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酶学
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生物信息学
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环境生物技术
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工业生物技术
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结构生物学
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产品关联
DOI
PubMed
高影响因子
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