PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
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2024
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IF 2.6
Jingmou Yu,Mengqi Liu,Chao Zhang,Lizhen Cheng,Changchun Peng,Dengzhao Jiang,Wenbo Liu,Hongguang Jin,Jin Ren
Herein, we designed and synthesized novel reactive oxygen species (ROS)-responsive glycol chitosan-doxorubicin (DOX) prodrug via a ROS-cleavable thioketal (TK) linker. The obtained GC-TK-DOX formed self-assembled nanoparticles of 312 nm in aqueous media. Photosensitizers zinc phthalocyanine (ZnPc)-loaded GC-TK-DOX (GC-TK-DOX/ZnPc) nanoparticles were fabricated by using a dialysis approach. The GC-TK-DOX and GC-TK-DOX/ZnPc nanoparticles were nearly spherical by transmission electron microscopy (TEM) observation. Under 660-nm laser irradiation, GC-TK-DOX/ZnPc could generate singlet oxygen. Further, GC-TK-DOX/ZnPc nanoparticles exhibited ROS-sensitive release of DOX and ZnPc in vitro. GC-TK-DOX/ZnPc with laser irradiation showed more drug uptake and higher cytotoxic effects than GC-TK-DOX/ZnPc without irradiation, free DOX and GC-TK-DOX in HeLa tumor cells. Overall, these findings suggested that GC-TK-DOX/ZnPc could be a promising nanoarchitecture for synergetic chemo-photodynamic therapy against tumors.
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Nature Communications
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2024
·Vol. 15
·期 1
·1-13
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IF 14.7
Xia Mengmeng,Wang Qiyue,Liu Yamin,Fang Chunyan,Zhang Bo,Yang Shengfei,Zhou Fu,Lin Peihua,Gu Mingzheng,Huang Canyu,Zhang Xiaojun,Li Fangyuan,Liu Hongying,Wang Guangfeng,Ling Daishun
Targeted assembly of nanoparticles in biological systems holds great promise for disease-specific imaging and therapy. However, the current manipulation of nanoparticle dynamics is primarily limited to organic pericyclic reactions, which necessitate the introduction of synthetic functional groups as bioorthogonal handles on the nanoparticles, leading to complex and laborious design processes. Here, we report the synthesis of tyrosine (Tyr)-modified peptides-capped iodine (I) doped CuS nanoparticles (CuS-I@P1 NPs) as self-catalytic building blocks that undergo self-propelled assembly inside tumour cells via Tyr-Tyr condensation reactions catalyzed by the nanoparticles themselves. Upon cellular internalization, the CuS-I@P1 NPs undergo furin-guided condensation reactions, leading to the formation of CuS-I nanoparticle assemblies through dityrosine bond. The tumour-specific furin-instructed intracellular assembly of CuS-I NPs exhibits activatable dual-modal imaging capability and enhanced photothermal effect, enabling highly efficient imaging and therapy of tumours. The robust nanoparticle self-catalysis-regulated in situ assembly, facilitated by natural handles, offers the advantages of convenient fabrication, high reaction specificity, and biocompatibility, representing a generalizable strategy for target-specific activatable biomedical imaging and therapy.
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FOOD RESEARCH INTERNATIONAL
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2024
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IF 7
Zihuan Wu,Haiqin Chen,Bo Yang,Jianxin Zhao,Wei Chen
The study aimed to determine the chemical structures of octadecatrienoic acid isomers produced by probiotics through the bioconversion of α-linolenic acid and to assess their antioxidant capacities. The chemical structures were identified using nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS), while the antioxidant capacities were evaluated in vitro and in cellular. The NMR signals obtained allowed for definitive characterization, with the main ion fragments detected being m / z 58.0062, 59.0140, 71.0141, 113.0616, 127.0777, and 181.5833. Compounds at concentrations below 40 μM maintained the antioxidant capacity of HepG2 cells by protecting endogenous antioxidative enzymes and mitochondrial membrane potential. However, doses higher than 40 μM increase oxidative damage and mitochondrial dysfunction. These results confirmed the structure of the probiotic-derived compound as trans9, trans11, cis15-conjugated linolenic acid. Additionally, appropriate doses of CLNA can alleviate oxidative stress induced by AAPH, while high doses aggravate cellular damage. These findings provide foundational information for the further exploration of probiotic-derived edible lipids.
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Food Analytical Methods
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2024
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IF 2.6
Hu Rui,Wu Yijun,He Haoliang,Chen Wentao,Xiang Leiwen,Huang Dihui
A reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed to quantify nine gout-related compounds: uric acid, guanine, hypoxanthine, adenine, xanthine, inosine, guanosine, xanthosine, and adenosine. Separation was achieved using a Supersil AQ-C18 column with mobile phase solution A (water:triethylamine:phosphoric acid, 950:11:5, pH 3.93) and solution B (water:acetonitrile, 90:10). The method demonstrated good linearity with linear ranges for nucleosides (1.06–17.00 μg mL −1 ), purines (3.13–50.00 μg mL −1 ), and uric acid (12.50–200.00 μg mL −1 ). The recoveries of analytes in spiked samples ranged from 99.97 to 103.30%. The limit of detection was 1.45 μg mL −1 . This method is characterized by high precision and accuracy, a wide linear range, good reproducibility, and effective quantification of the nine gout-related compounds. The method has been successfully applied to the detection and evaluation of the representative Min cuisine dish, “Buddha Jumps Over the Wall.”
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Marine Drugs
·
2025
·Vol. 23
·期 4
·146
·
IF 5.4
Jingjing Du,Xuening Zhang,Kaiqiang Guo,Wanjun Lin,Wenjian Lan,Zi Wang,Meina Shi,Zifeng Huang,Houjin Li,Wenzhe Ma
Triple-negative breast cancer (TNBC) presents a significant therapeutic challenge due to the absence of specific targeted treatments. In this study, we explored the therapeutic potential of xanthocillin X dimethyl ether (XanDME), a naturally occurring isocyanide isolated from the marine fungusScedosporium apiospermum, on TNBC. To elucidate the underlying mechanism, we initially demonstrated that XanDME directly binds to hemin, the oxidized form of heme, in vitro, corroborating previous reports. This interaction led to the depletion of intracellular regulatory heme. We further established that XanDME translocates into the mitochondria, where it interacts with crucial hemoproteins, namely cytochromes. The binding of XanDME with mitochondrial cytochromes disrupts the electron transport chain (ETC), inhibits the activity of mitochondrial complexes, and inactivates mitochondrial respiration. The inhibitory activity of XanDME on mitochondrial function significantly contributes to its anti-TNBC effects, as observed both in vitro and in vivo. Our study underscores the potential of XanDME against TNBC, warranting further investigations.
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NEW JOURNAL OF CHEMISTRY
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2024
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IF 2.7
Jiamin Wang,Hao Lin,Mengli Liu,Bo Xiong,Dingyuan He,Jiasheng Tu,Dongsheng He
Cationic polymers are a class of promising carriers for nucleic acid delivery. However, the balance between biosafety and transfection efficiency is still a major obstacle for nucleic acid delivery. Accurate structural design can effectively evaluate the relationship between structural factors and nucleic acid delivery. Previous series of vectors optimized based on artificial amino acid Stp have been shown to effectively improve gene transfection. Here, a series of sequenced-defined oligomers containing hydrophobic oleic acid with different topologies, different charge densities and with or without crosslinking cystine domains were designed and synthesized for a better understanding of the structure activity relationship. The oligomers were further mixed with either pDNA or siRNA to form polyplexes. The particle size, zeta potential, polyplexes formation properties, in vitro stability and reductive responsiveness of the polyplexes were investigated. In addition, studies regarding the transfection efficiency, cellular uptake, cellular trafficking, cytotoxicity and hemolysis were performed. The resulting oligomers display general good complexation ability with pDNA and siRNA with enhanced stability and redox sensitivity. some of the oligomers showed adequate or surpassed transfection efficiency compared with PEI. The polyplexes formed with oligomer #1 have good cellular uptake and endo-lysosome escape property. In addition, all the oligomers and the polyplexes showed low cytotoxicity and hemolysis, demonstrated high biocompatibility. In summary, the results evidenced that proper charge density with hydrophobic oleic acid and thiol crosslinking cystine improves the overall performance of delivering pDNA and siRNA.
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JOURNAL OF MOLECULAR STRUCTURE
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2024
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IF 4
Hu Wang,Pengxiao Guo,Yadong Zhou,Chaochuang Yin,Yizhu Lei,Renshu Wang,Yinyan Wang,Tingting Wu,Ziao Zong
Two mononuclear Copper(II) complexes, identified as [Cu(C 10 H 8 NO 4 F)(C 6 H 7 N)] ( C1 ) and [Cu(C 10 H 8 NO 4 F)(C 12 H 8 N 2 )]·H 2 O·CH 3 OH ( C2 ), incorporating a tridentate Schiff-base ligand with an ONO coordination (C 10 H 8 NO 4 F = 5-fluoro-2-hydroxybenzylidene-L‑serine) and two unique auxiliary ligands (C 6 H 7 N = 4-methylpyridine and C 12 H 8 N 2 = 1,10-phenanthroline) were developed and detailed structurally. Density functional theory (DFT) evaluations of these complexes employed Becke's three-parameter hybrid (B3LYP) approach within the Gaussian 16 computational package. The outcomes from computational analysis corresponded with experimental data. Additionally, the inhibition capabilities of complexes C1 and C2 were evaluated in vitro targeting jack bean urease. Simultaneously, molecular docking was utilized to determine potential binding interactions. Experimental results and docking analyses showed that C1 had considerable inhibitory strength (IC 50 = 2.44 ± 0.15 μM) relative to the benchmark control, acetohydroxamic acid (IC 50 = 27.73 ± 2.93 μM). Furthermore, a 100-ns molecular dynamics assessment was performed to examine the interaction stability of urease with C1 and C2 , using the Desmond 2021 tool from Schrödinger. The correlation between structural configurations and inhibition efficacy was further explored through molecular docking, density functional theory analysis, and molecular dynamics evaluations.
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Nature Communications
·
2024
·Vol. 15
·期 1
·1-17
·
IF 14.7
Li Xi,Yu Linwei,Liu Xikai,Shi Tianyi,Zhang Yu,Xiao Yushuo,Wang Chen,Song Liangliang,Li Ning,Liu Xinran,Chen Yuchen,Petersen Robert B.,Cheng Xiang,Xue Weikang,Yu Yanxun V.,Xu Li,Zheng Ling,Chen Hong,Huang Kun
Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) are neurodegenerative disorders characterized by the accumulation of α-synuclein aggregates. α-synuclein forms droplets via liquid-liquid phase separation (LLPS), followed by liquid-solid phase separation (LSPS) to form amyloids, how this process is physiologically-regulated remains unclear. β-synuclein colocalizes with α-synuclein in presynaptic terminals. Here, we report that β-synuclein partitions into α-synuclein condensates promotes the LLPS, and slows down LSPS of α-synuclein, while disease-associated β-synuclein mutations lose these capacities. Exogenous β-synuclein improves the movement defects and prolongs the lifespan of an α-synuclein-expressing NL5901 Caenorhabditis elegans strain, while disease-associated β-synuclein mutants aggravate the symptoms. Decapeptides targeted at the α-/β-synuclein interaction sites are rationally designed, which suppress the LSPS of α-synuclein, rescue the movement defects, and prolong the lifespan of C. elegans NL5901. Together, we unveil a Yin-Yang balance between α- and β-synuclein underlying the normal and disease states of PD and DLB with therapeutical potentials.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Chaoting Wen,Jialuo Tang,Maowei Wu,Huimin Liu,Xinying Lin,Meidi Fan,Guoyan Liu,Jixian Zhang,Li Liang,Xiaofang Liu,Youdong Li,Yuqing Duan,Xin Xu
Quercetin (Que) is a polyhydroxy flavonoid with strong inhibitory activity against cancer cells. However, the poor water solubility and low bioavailability of Que. limit its application in the functional food industry. In the present study, the nanoparticle loaded with Que. was prepared with whey isolate protein (WPI) stabilized by triphenylphosphonium bromide (TPP) and pectin (P) as wall materials. The formation mechanism, release of Que., and antitumor activity of nanoparticles were investigated. The results showed that the optimal ratio of WPI: TPP: Que.: P in the preparation of nanoparticles (WPI-TPP-Que-P) was 50:8:1:20 ( w /w/ w /w). The encapsulation rate of Que. in the WPI-TPP-Que-P was 82.64 % with a particle size of 261.7 nm and a zeta potential of −42.1 mV. Compared with WPI-TPP-Que, the retention rate of WPI-TPP-Que-P increased by 4.03 % after in vitro digestion. The release kinetic result indicated that WPI-TPP-Que-P release was dominated by non-Fickian diffusion. In addition, WPI-TPP-Que-P was taken in and achieved intracellular targeting to mitochondria and promoted apoptosis (apoptosis rate: 83.6 %) by decreasing mitochondrial membrane potential and IL-10 content and improving the content of TNF-α in HepG-2 cells. This study highlights the promising application of P-modified mitochondria-targeted nanocarriers for enhanced Que. delivery.
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Chem
·
2025
·
IF 19.6
Xinyuan Bi,Xiaohang Qian,Bingsen Xue,Miao Zhang,Shuyu Liu,Haoran Chen,Cheng Jin,Huidong Tang,Jian Ye
Multiplexed detection is a challenging yet essential task in analytical chemistry, especially for complex systems. Surface-enhanced Raman spectroscopy (SERS) is a promising analytical tool due to its molecular fingerprinting capability, sensitivity, low cost, and tractability. Considering the molecular profusion and diversity, SERSome, namely, spectral set, facilitates robust detection but is still challenged by spectral overlapping-induced uncertainty of molecular assignment and multiplexed quantification. Herein, we introduce molecule-resolvable (MORE) SERSome, identifying specific analytes contributing to the complex SERS spectra, which are then used in spectral decomposition for multiplexed analysis. Taking metabolic profiling for Alzheimer’s disease as a proof of concept, ten metabolites are screened in human serum. A deep-learning model enables accurate and rapid diagnosis, achieving an area under the receiver operating characteristic curve as high as 91.5%. Comparing with conventional methods, MORE SERSome presents a methodological advancement in multiplexed detection with strong potential for general applications and fundamental research in analytical chemistry.
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Cancer Communications
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2025
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IF 24.9
Jie Zhang,Chen Zhang,Ruichen Zang,Weiwu Chen,Yining Guo,Haofei Jiang,Jing Le,Kunyu Wang,Haobo Fan,Xudong Wang,Sisi Mo,Peng Gao,Wenhao Guo,Xinrong Jiang,Fengbin Gao,Junming Jiang,Juyan Zheng,Yuxing Chen,Yicheng Chen,Yanlan Yu,Guoqing Ding
Background: Only a few bladder cancer patients benefit from anti-programmed cell death protein 1/programmed cell death ligand 1 immunotherapy. The cluster of differentiation 47 (CD47) plays an important role in tumor immune evasion. CD47 is a highly glycosylated protein, however, the mechanisms governing CD47 glycosylation and its potential role in immunosuppression are unclear. Therefore, this study aimed to evaluate the function of CD47 glycosylation in bladder cancer. Methods: Western blotting, immunohistochemistry, and flow cytometry were used to measure protein expression, protein-protein interactions, and phagocytosis in bladder cancer. A murine model was employed to investigate the impact of mannosidase alpha class 1B member 1 (MAN1B1) modification of CD47 on anti-phagocytosis in vivo. An ex vivo model, patient-derived tumor-like cell clusters, was used to examine the effect of targeting MAN1B1 on phagocytosis. Results: Our research identified that aberrant CD47 glycosylation was responsible for its immunosuppression. The glycosyltransferase MAN1B1 responsible for CD47 glycosylation was highly expressed in bladder cancer. Abnormal activation of extracellular signal-regulated kinase (ERK) was significantly associated with MAN1B1 stability by regulating the interaction between MAN1B1 and the E3 ubiquitin ligase HMG-CoA reductase degradation 1 (HRD1). Mechanistically, abnormally activated ERK stabilized MAN1B1, resulting in the glycosylation of CD47 and facilitating immune evasion by enhancing its interaction with signal-regulatory protein alpha (SIRP-α). In vitro and in vivo experiments demonstrated that MAN1B1 knockout weakened CD47-mediated anti-phagocytosis. MAN1B1 inhibitors promoted phagocytosis without causing anemia, offering a safe alternative to anti-CD47 therapy. Conclusions: This comprehensive analysis uncovered that ERK activation stabilizes MAN1B1 by regulating the interaction between MAN1B1 and HRD1, facilitates immune evasion via CD47 glycosylation, and presents new potential targets and strategies for cancer immunotherapy that do not cause anemia.
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ADVANCED MATERIALS
·
2025
·
IF 26.8
Dazhi Chen,Li Yang,Shulan Ni,Chaofan Jin,Chunyi Xu,Xingjie Zan,Yang Wang,Hong Zhu
Developing high-payload systems that dynamically respond to physiological fluctuations is crucial not only for improving the precision, safety, and efficacy of protein therapies but also for addressing biosafety concerns associated with carriers, reducing administration frequency, minimizing infection risks, and enhancing patient compliance. However, achieving precise control over protein release in the high-payload carriers remain a major challenge. In this study, a physiology-responsive, high-payload insulin (Ins) granule is engineered for long-term glucose management, using Ins as a model—an essential hormone that must be released in response to blood glucose changes for effective glycemic control in diabetic patients. The [(Ins&GOx)@Zn]@[TA&Fe] granules achieve an Ins loading capacity (LC%) exceeding 80%, significantly higher than the previously reported maximum of ≈40%. These granules extend the glucose-regulating effect of free Ins, typically limited to 3 h, to 6 days with a single injection, without any observed risk of hypoglycemia. Long-term administration (28 days, 4 injection cycles, 7 days injection −1 ) shows no significant physiological toxicity or immune response. This approach offers a promising strategy for developing intelligent, high-payload delivery systems for protein-based therapeutics, advancing more precise, safe, and patient-compliant treatments.
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