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PLANT PHYSIOLOGY AND BIOCHEMISTRY · 2024 · IF 6.1

NRT2.1 mediates the reciprocal regulation of nitrate and NO/SNO in seedling leaves of Fraxinus mandshurica and Betula platyphylla

Bo Wang,Xiaoshuang Li,Shuyi Han,Haixin Yang,Yaguang Zhan,Guizhi Fan

Nitric oxide (NO) and S-nitrosothiol (SNO) are signal molecules and the products of nitrogen metabolism. Nitrate (NO 3 − ) is the main nitrogen source, and nitrate transporters (NRTs) are responsible for NO 3 − absorption or transport. However, the interactive effect between NO 3 − /NRT and NO/SNO in tree plants remains ambiguous. In the present study, 25 mmol L −1 NO 3 − and 1 mmol L −1 NO donor sodium nitroprusside (SNP) treatment that was conducted for 24 h enhanced NO/SNO and NO 3 − metabolism, whereas 2.5 mmol L −1 NO 3 − and 80 μmol L −1 N6022 (a compound that increases SNO content) treatment reduced them in seedling leaves of Fraxinus mandshurica and Betula platyphylla . Among the nine NRT family members examined, the gene expression level of NRT2.1 had a greater response to NO/SNO and NO 3 − treatment in the seedling leaves of F. mandshurica and B. platyphylla . Meanwhile, FmNRT2.1 mediated NO and SNO production in seedling leaves of F. mandshurica using Agrobacterium -mediated transient transformation. These findings shed light on the reciprocal regulation between NO 3 − and NO/SNO in seedlings of F. mandshurica and B. platyphylla , and NRT2.1 may act as a key regulatory hub.

CAS / MDL: 7757-79-1
研究领域: 植物生理学 · 分子生物学 · 植物生物化学
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JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY · 2025 · IF 4.7

A Ti3C2Tx-based nanosystem triggers in situ nitric oxide release to boost the antibacterial capability of scaffolds

Wenjie Ma,Ru Jia,Lanlan Dong,Cijun Shuai,Wurikaixi Aiyiti,Chongxian He

Transplant-associated bacterial infections, especially the formation of bacterial biofilms, frequently lead to persistent infections and even transplant failure. Herein, a near-infrared laser-triggered nanosystem with antibacterial and anti-biofilm activities is constructed by loading S-nitrosothiols (RSNO) onto Ti 3 C 2 T x nanosheets, which are then mixed with poly-L-lactic acid (PLLA) powders to prepare porous PLLA/Ti 3 C 2 T x -SNO scaffolds. Especially, the excellent photothermal property of the scaffold is expected not only to eliminate bacterial biofilms but also to trigger RSNO molecules to in situ release nitric oxide (NO) gas under near-infrared laser irradiation. Moreover, the removal of the biofilms facilitates more NO to enter and kill the deep bacteria through nitridation damage, thus realizing the synergistic antibacterial capabilities of photothermal and NO gas therapies. The experimental results showed that the photothermal conversion efficiency of the scaffold reached 39 %. Combining with the in situ NO release, the scaffold presented excellent anti-biofilm and antibacterial activities, with antibacterial rates of 93.6 % and 94.9 % against E. coli and S. aureus , respectively. This work is expected to solve the dilemma of treating bacterial infections in deep tissues, providing reference for the clinical treatment of transplant-associated bacterial infections and even extending to the treatment of other deep refractory infections.

研究领域: 纳米技术 · 抗菌治疗 · 光热治疗 · 生物材料 · 传染病
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REACTIVE & FUNCTIONAL POLYMERS · 2023 · IF 5.1

Noninterventional target-embolization combined with NO gas therapy for solid tumors by pH-responsive poly(amino acid)s with S-nitrosothiols group

Zhengpeng Chen,Lei Wang,Yuanyuan Jin,Hongyun Guo,Yongdong Zhang,Mingzhong Ma,Xiaobo Wang,Xing Zhou,Ziqiang Lei,Dedai Lu

Gas therapy and embolization are important treatment methods for solid tumors. In order to improve the efficacy of NO therapy and simplify the operation of interventional embolization, we designed and prepared the microacidic-gelled poly[(L-Glutamic acid- ran -L-Tyrosine)- b -L-Threonine- b -L-S-nitrosocysteine]s (PGTTSNCs, obtained by the reaction of tert-butyl nitrite with thiol side groups of poly[(L-Glutamic acid- ran -L-Tyrosine)- b -L-Threonine- b -L-Cysteines]s, PGTTCs.) for noninterventional embolization combined with NO gas therapy for solid tumors. The results of in vivo experiments indicated that PGTTSNCs from PGTTCs-6.4 (the gelled-pH value is 6.4) has significant target-accumulation and therapy effects, and at 10 days post-injection only scars were found at the tumor site. After 20 days, the tumors of model mice were completely disappeared. The method is extremely simple and efficient for solid tumors, which is not only a great innovation of tumors theranostic, but also a qualitative development in nanomaterials .

研究领域: 肿瘤学 · 纳米医学 · 生物材料学
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION · 2024 · IF 3.6

Electrospun membranes of diselenide-containing poly(ester urethane)urea for in situ catalytic generation of nitric oxide

Yong Gao,Shan Bai,Kongying Zhu,Xiaoyan Yuan

Nitric oxide (NO) plays an important role as a signalling molecule in the biological system. Organoselenium-coated or grafted biomaterials have the potential to achieve controlled NO release as they can catalyse decomposition of endogenous S-nitrosothiols to NO. However, such biomaterials are often challenged by the loss of the catalytic sites, which can affect the stability in tissue repair applications. In this work, we prepare a diselenide-containing poly(ester urethane)urea (SePEUU) polymer with Se–Se in the backbone, which is further electrospun into fibrous membranes by blending with poly(ester urethane)urea (PEUU) without diselenide bonds. The presence of catalytic sites in the main chain demonstrates stable and long-lasting NO catalytic activity, while the porous structure of the fibrous membranes ensures uniform distribution of the catalytic sites and better contact with the donor-containing solution. PEUU/SePEUU50 in 50/50 mass ratio has a physiologically adapted rate of NO release, with a sustained generation of NO after exposure to PBS at 37 °C for 30 d. PEUU/SePEUU50 has a low hemolysis and protein adsorption, with mechanical properties in the wet state matching those of natural vascular tissues. It can promote the adhesion and proliferation of human umbilical vein endothelial cells in vitro and control the proliferation of vascular smooth muscle cells in the presence of NO generation. This study exhibits the electrospun fibrous membranes have potential for utilizing as hemocompatible biomaterials for regeneration of blood-contacting tissues.

CAS / MDL: 822-06-0 57564-91-7
研究领域: 生物材料科学 · 组织工程 · 生物医学工程 · 药学
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Theranostics · 2020 · IF 8.579

S-nitrosothiols loaded mini-sized Au@silica nanorod elicits collagen depletion and mitochondrial damage in solid tumor treatment

Ping Liu,Yidan Wang,Yang Liu,Fengping Tan,Jining Li,Nan Li

To a large extent, the dense extracellular matrix (ECM), which tightly connects tumor cells to arm the tumor into an intractable fortress, significantly decreases the nanoparticles delivery efficacy and overall performance in cancer treatments. Therefore, it is necessary to transform the dense stroma of solid tumors to loose state, which could realize deep penetration of nanomedicine and enhance cancer treatment effects. Here, we fabricated a protein-free collagen nanosweeper, triphenylphosphonium bromide (TPP) coated and S-nitrosothiols loaded mini-sized Au@silica nanorod (Au@SiO 2 -SNO/PEG/TPP, GSNP-TPP), to clear the transport barriers of nanoparticles as well as elevate enhanced permeability and retention (EPR) effect, thus alleviating the diffusion resistance and realizing further penetration of nanoparticles. Methods: By modifying the Au@silica with thermo-sensitive S-nitrosothiols, the carrier could release the nitric oxide (NO) due to the surface overheat as well as perform photothermal therapy (PTT) under near-infrared (NIR) laser irradiation. The level of collagen depletion was observed via western blotting and immunofluorescent staining. In addition, the dual-imaging and antitumor efficiency of GSNP-TPPs were evaluated with the HeLa tumor-bearing mouse model. Results: On one hand, the released NO could deplete collagen by activating matrix metalloproteinases (MMPs) to break collagen fibers, thus loosening the dense ECM to enhance the cellular internalization. On the other hand, with the mitochondrial-targeted effect of TPP, the diffusible NO in tumor might rapidly interact with superoxide anion (O 2 Ÿ - ) to produce highly toxic and powerful reactive nitrogen species (RNS) -- peroxynitrite (ONOO - ), which resulted in mitochondrial damage to induce cell apoptosis. With the unique properties of mini-sized gold nanorods, the formulated nanoparticles exhibited good computed tomography (CT) and multi-spectral optoacoustic tomography (MSOT) imaging effects in precisely locating and monitoring tumor. Moreover, the antitumor efficacy of GSNP-TPPs + laser group was further confirmed by ex-vivo histological analysis of tumor tissue. Conclusion: This work points out a strategy to overcome the obstacle standing in nanoparticles penetration, and opens the door of further exploitation of NO-related theranostic systems.

CAS / MDL: 1336-21-6
研究领域: 癌症治疗 · 纳米技术 · 生物医学工程 · 药学
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2022 · IF 9.965

Pillar[5]arene based glyco-targeting nitric oxide nanogenerator for hyperthermia-induced triple-mode cancer therapy

Yang Wang,Yafei Wen,Yun Qu,Zhichao Pei,Yuxin Pei

Nitric oxide (NO)-mediated gas therapy (GT) and alkyl radical (R•) therapy (ART) are emerging cancer therapy modes, and multi-mode therapy has been recognized as an attractive strategy for enhancing anti-cancer efficacy. In this work, a thermal-responsive R• initiator 2,2′-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIBI)-loaded glycol-targeting NO nanogenerator was constructed by first the covalent conjugation of thermal-responsive NO donor of S-nitrosothiols (RSNO) on the surface of mesoporous silica-coated gold nanorods ( [email protected] ), then the coating of a supramolecular complex of amino pillar[5]arene (NP5) and galactose derivative (G), and finally the loading of AIBI. The glycol-targeting NO nanogenerator demonstrated specific targeting ability to HepG2 cells owing to the recognition between galactose residues and asialoglycoprotein receptors (ASGPR). Specially, upon 808 nm near-infrared (NIR) irradiation, the AIBI-loaded NO nanogenerator generated hyperthermia to achieve photothermal therapy (PTT), and further GT and ART resulted from the thermal responsiveness of RSNO and AIBI, respectively. In vitro experiments revealed that the AIBI-loaded glyco-targeting NO nanogenerator had good biocompatibility and exhibited effective inhibition to the proliferation of HepG2 cells. This work provides a novel way to supramolecular hybrid drug delivery systems for triple-mode targeting therapy of PTT/GT/ART.

研究领域: 癌症治疗 · 纳米技术 · 药学 · 材料科学 · 生物医学工程
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Nano Today · 2022 · IF 18.962

NIR responsive nitric oxide nanogenerator for enhanced biofilm eradication and inflammation immunotherapy against periodontal diseases

Manlin Qi,Xuan Ren,Wen Li,Yue Sun,Xiaolin Sun,Chunyan Li,Siyao Yu,Lin Xu,Yanmin Zhou,Shuyan Song,Biao Dong,Lin Wang

Periodontal disease is one of the most common oral infectious diseases and closely related to many systemic diseases which is in urgent need of novel and effective drugs. In particular, the problems of deep lesion location and synchronization of antibacterial and anti-inflammatory needs to be addressed. Herein, near infrared (NIR) light triggered nanoplatform with antibacterial and anti-inflammatory dual-functions by antibacterial photodynamic therapy (aPDT), photothermal therapy (PTT) and gas therapy was realized by loading S-nitrosothiols (SNO) and ICG into mesoporous silica-coated gold nanorods . Using a single 808 nm NIR light, the excellent antibacterial efficacy can be achieved not only by aPDT-induced bacteria killing but also by PTT-triggered biofilm dispersal. Furthermore, SNO molecules would also be thermally activated to release nitric oxide (NO) gas molecules at the site of periodontal disease, exerting inflammation inhibition by suppressing the assembly of pro-inflammatory factors and NLRP3 inflammasome. Additionally, such nanoplatform could validly combat pathogenic bacterial biofilm, and modulate the inflammatory immunity, leading to favorable therapeutics on animal models with periodontal diseases. Hence, this design provides an effective solution to solve the problems of deep tissue treatment along with simultaneously antibacterial/anti-inflammatory capabilities, which provides a bright prospect for clinical treatment of periodontal diseases, even extended to other refractory infections in deep sites.

CAS / MDL: 2044-85-1 5471-63-6
研究领域: 牙科学 · 药学 · 生物医学工程 · 免疫学
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