COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Shu Wu,Jinjing Shi,Xia Chen,Lu Bai,Qiuhua Wu,Guolin Zhang
Novel multi-responsive drug delivery vehicles (CDs/ [email protected] ) were prepared by grafting amino-terminated poly (N-vinyl caprolactam) (PNVCL-NH 2 ) and amino-rich carbon dots (CDs) on the surface of aldehyde-functionalized HMSNs (HMSNs-CHO) via Schiff base reaction. The CDs were prepared from L -arginine and their surfaces were rich in guanidine . Doxorubicin (DOX) was loaded into the nanoparticles to form drug loaded vehicles (CDs/ [email protected] ) and the drug loading efficiency was 58.38%. The drug release behaviors of CDs/ [email protected] showed temperature and pH responsiveness due to the poly (N-vinyl caprolactam) (PNVCL) and Schiff base bond. The high concentration of NO released in high concentration H 2 O 2 of tumor site could induce tumor cells apoptosis. The multi-responsive CDs/ [email protected] are intriguing drug carriers, which combine drug delivery and NO release in one.
研究领域:
纳米技术
·
药学
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2024
·
IF 10.7
Shengnan Huang,Chenyang Zhou,Chengzhi Song,Xiali Zhu,Mingsan Miao,Chunming Li,Shaofeng Duan,Yurong Hu
Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an in situ injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor resection cavity. The MPB-NO@DOX + ATRA gel was fabricated by mixing a thrombin solution, a fibrinogen solution containing all-trans retinoic acid (ATRA), and a Mn/NO-based immune nano-activator termed MPB-NO@DOX. ATRA promoted the differentiation of cancer stem cells, inhibited cancer cell migration, and affected the polarization of tumor-associated macrophages. The outer MnO 2 shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn 2+ and produce O 2 , resulting in the release of doxorubicin (DOX). The released DOX entered the nucleus and destroyed DNA, and the fragmented DNA cooperated with Mn 2+ to activate the cGAS-STING pathway and stimulate an anti-tumor immune response. In addition, when MPB-NO@DOX was exposed to 808 nm laser irradiation, the Fe-NO bond was broken to release NO, which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment. In conclusion, the MPB-NO@DOX + ATRA gel exhibited excellent anti-tumor efficacy. The results of this study demonstrated the great potential of in situ injectable hydrogels in preventing postoperative tumor recurrence.
研究领域:
肿瘤学
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生物材料学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Li Yan,Ge Jingping,Yin Yuanyuan,He Juan,Shang Longcheng
Background: This study aimed to explore the regulatory effect of anserine on HUVEC cell injury and thrombosis in deep venous thrombosis (DVT) rats, and to elucidate the underlying molecular mechanisms.Methods: Non-targeted metabolomics data analyses were conducted using an ultra-performance liquid chromatography system Vanquish UHPLC and mass spectrometer to detect plasma metabolism profiles. The transcriptome sequencing and gene intervention experiments were performed to verify the regulatory effect. Further in vivo and in vitro experiments were performed. Enzyme-linked immunosorbent assay was used to detect the levels of P-selectin, E-selectin, and vWF, hematoxylin-eosin (HE) staining was performed to observe thrombotic and inflammatory cell infiltration, flow cytometry and TUNEL assays were performed to detect apoptosis, and qPCR and WB assays were conducted to determine the gene and protein expression.Results: Anserine alleviated HUVECs injury, reduced adhesion molecule expression, and inflammation. It decreased P-selectin, E-selectin, vWF, THBD, TFPI levels, and apoptosis while promoting NOS3, ET-1, and NO release in HUVECs. In DVT rats, anserine reduced P-selectin, E-selectin, vWF, thrombosis, cell infiltration, apoptosis, and promoted NO release. Transcriptome sequencing and gene intervention confirmed anserine’s regulation of the PI3K-Akt pathway and coagulation via MYB. CARNMT1, a regulatory enzyme for anserine metabolism, increased anserine content, inhibiting coagulation, thrombosis, cell infiltration, and promoting NO release in rats.Conclusion: This study confirmed anserine could alleviate DVT by improving the inflammatory response, inhibiting blood agglutination, and promoting vasodilation, providing new potential therapeutic targets, important scientific evidence for the development of DVT management, and new clues for an in-depth understanding of its molecular mechanisms.
研究领域:
药理学
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分子生物学
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心血管疾病
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血栓
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2020
·Vol. 18
·期 1
·1-25
·
IF 6.518
Zhao Baohua,Wang He,Dong Wenjing,Cheng Shaowen,Li Haisheng,Tan Jianglin,Zhou Junyi,He Weifeng,Li Lanlan,Zhang Jianxiang,Luo Gaoxing,Qian Wei
Background Infectious diseases caused by multidrug-resistant (MDR) bacteria, especially MDR Gram-negative strains, have become a global public health challenge. Multifunctional nanomaterials for controlling MDR bacterial infections via eradication of planktonic bacteria and their biofilms are of great interest.Results In this study, we developed a multifunctional platform (TG-NO-B) with single NIR laser-triggered PTT and NO release for synergistic therapy against MDR Gram-negative bacteria and their biofilms. When located at the infected sites, TG-NO-B was able to selectively bind to the surfaces of Gram-negative bacterial cells and their biofilm matrix through covalent coupling between the BA groups of TG-NO-B and the bacterial LPS units, which could greatly improve the antibacterial efficiency, and reduce side damages to ambient normal tissues. Upon single NIR laser irradiation, TG-NO-B could generate hyperthermia and simultaneously release NO, which would synergistically disrupt bacterial cell membrane, further cause leakage and damage of intracellular components, and finally induce bacteria death. On one hand, the combination of NO and PTT could largely improve the antibacterial efficiency. On the other hand, the bacterial cell membrane damage could improve the permeability and sensitivity to heat, decrease the photothermal temperature and avoid damages caused by high temperature. Moreover, TG-NO-B could be effectively utilized for synergistic therapy against the in vivo infections of MDR Gram-negative bacteria and their biofilms and accelerate wound healing as well as exhibit excellent biocompatibility both in vitro and in vivo.Conclusion sOur study demonstrates that TG-NO-B can be considered as a promising alternative for treating infections caused by MDR Gram-negative bacteria and their biofilms.
研究领域:
生物医学工程
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传染病学
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纳米技术
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微生物学
✓ 已验证
DOI
PubMed
高影响因子
INORGANIC CHEMISTRY
·
2022
·
IF 5.436
Yuhao Wu,Yirong Wang,Yun Sun,Zhen Li,Xianghong Li,Zhiguo Zhou,Dingguo Tang
A novel family of ruthenium nitrosyl complexes [Ru(bpy)(C∧N)(MeCN)NO](PF6)2 (2a–2e, bpy = 2,2′-bipyridine, HC∧N = 2-phenylpyridine and its derivatives) has been prepared by reacting cyclometalated ruthenium complexes [Ru(bpy)2(C∧N)][PF6] (1a–1e) with NO+, which were comprehensively characterized by mass, IR, NMR, and UV–vis spectra as well as the single-crystal X-ray structure determinations. Herein, the coordination geometry of Ru atoms in 2a–2e is a distorted octahedron and {RuII–NO+}6 is present in these complexes. Theoretical calculations suggest that the reactions involving dissociation of one bipyridine and coordination with NO+ proceed spontaneously (ΔG < 0) and the transformation from 1a–1e to the intermediates is dominated by substituents (ΔGRI varies from −1.19 to −1.53 eV), which influence the binding energy between Ru(II) and NO+ in complexes 2a–2e (−89.42 to −101.17 kcal/mol) and thus control the photorelease of NO on a certain scale. The weak absorption bands in the visible region could be attributed to the contribution of dπ(RuII) → π*(NO+), which were enhanced greatly under light, indicating the possible release of NO. The photoinduced NO, as well as singlet oxygen (1O2), was then confirmed by EPR spectra, and the amount of NO released from 2a–2e was estimated via Griess reagent assay. The cytotoxicity of these complexes with or without visible light irradiation was also investigated using an MTT assay.
研究领域:
无机化学
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配位化学
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光化学
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生物化学
✓ 已验证
DOI
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Mengsi Zhang,Hao Jin,Yi Liu,Lanlan Wan,Shuwei Liu,Hao Zhang
NO gas therapy is a supplementary approach for tumor treatment due to the advantages of minimal invasion, little drug resistance, low side effect and amplified efficacy. l -Arginine (L-Arg), a natural NO source with good biocompatibility, can release NO under the stimulation of H 2 O 2 in tumor microenvironment. However, the conventional l -Arg delivery systems via noncovalent loading usually lead to inevitable premature leakage of nano-cargos during blood circulation. In this work, an efficient l -Arg self-delivery supramolecular nanodrug (SDSND) for tumor treatment is demonstrated by combining Mannich reaction and π-π stacking. l -Arg links to (-)-epigallocatechin gallate (EGCG) with the assistance of formaldehyde through Mannich reaction, and then assembles into nanometer-sized particles via π-π stacking. The guanidine group of l -Arg and the phenolic hydroxyl groups of EGCG are preserved in the SDSNDs, which allows for accomplishing gas therapy by provoking tumor cell apoptosis and combining with EGCG to amplify apoptosis, respectively. In addition, the SDSNDs exhibit high biocompatibility and avoid the premature leakage of l -Arg in blood circulation, providing an alternative l -Arg delivery system for NO gas therapy. Statement of significance NO gas therapy has attracted emerging interest in tumor treatment. However, the controlled NO release and the avoidance of premature leakage of NO donors remain challenging. In this work, L-Arginine (L-Arg) self-delivery supramolecular nanodrug for efficient tumor therapy is demonstrated through the Mannich reaction of L-Arg, (-)-epigallocatechin gallate (EGCG) and formaldehyde. Stimulated by tumor microenvironment, the guanidine groups of L-Arg allow for accomplishing NO release and thus provoking tumor cell apoptosis. The nanodrug also avoids the premature leakage of L-Arg in blood circulation. Moreover, the preserved phenolic hydroxyl groups of EGCG combine with L-Arg to amplify apoptosis. The nanodrug exhibits high biocompatibility and good therapeutic effect, providing an alternative L-Arg delivery system for NO gas therapy.
研究领域:
药学
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纳米技术
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癌症治疗
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Communications
·
2024
·
IF 3.7
Shuo Yang,Nan Wang,Xiao–kun Ouyang,Yiwei Wu,Junhua Hu
Infection and inflammation are key factors affecting wound healing. Hydrogels are excellent wound dressings that provide a moist healing environment and serve as carriers for drugs or functional components. This work proposes a composite hydrogel, APLCE, composed of methyl methacrylate L-arginine (M-L-Arg) as an NO donor, synthesized through free radical polymerization with acrylamide (AM) and polyethylene glycol (PEG). The hydrogel matrix exhibits good water retention and mechanical properties. CaO 2 and ε-poly-L-arginine (EPL) are embedded in the hydrogel to form APLCE, where the hydrolysis of CaO 2 releases H 2 O 2 , triggering the release of arginine to release NO, inhibiting wound inflammation and bacterial growth. EPL added to the hydrogel synergistically with NO exhibits an antibacterial effect, with a bacterial inhibition rate exceeding 99 %. Animal experiments show that APLCE can completely eradicate bacteria in infected wounds, promote new skin formation, and achieve a wound closure rate of 94 % within 14 days. These findings emphasize the potential clinical application of APLCE as an innovative wound dressing material.
研究领域:
材料科学
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生物医学工程
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药学
·
伤口愈合
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2018
·Vol. 106
·期 12
·3239-3247
·
IF 3.231
Xiuzhen Wan,Pengcheng Liu,Xingxing Jin,Xuanxuan Xin,Pengfei Li,Jiang Yuan,Jian Shen
Nitric oxide (NO)-generating materials are beneficial for vascular tissue engineering (VTE) scaffold because the produced NO would enhance endothelial cells viability while inhibit smooth muscle cell (SMC) proliferation and reduce platelet adhesion, resulting in ideal hemocompatibility and endothelialization. Herein, poly(ε-caprolactone) (PCL)/keratin biocomposite mats were first fabricated, followed by in situ gold (Au) nanoparticles loading to afford PCL/keratin/AuNPs mats. These mats were characterized using field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The PCL/keratin/AuNPs mats were demonstrated to be capable of catalyzing NO release in the mimicked blood microenvironments. The generated NO could enhance human umbilical vein endothelial cell growth and inhibit human umbilical arterial SMC viability. In addition, these mats maintained the antibacterial activity of Au nanoparticles with good blood compatibility. Taken together, these keratin-based composite mats have potential usage in the VTE. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3239–3247, 2018.
研究领域:
生物材料
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组织工程
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生物医学材料
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2021
·
IF 8.128
Mengna Li,Na Li,Weiwang Qiu,Qian Wang,Jie Jia,Xueli Wang,Jianyong Yu,Xiaoran Li,Faxue Li,Dequn Wu
Infected wounds show delayed and incomplete healing processes and even render patients at a high risk of death due to the formed bacterial biofilms in the wound site, which protect bacteria against antimicrobial treatments and immune response. Nitric oxide based therapy is considered a promising strategy for eliminating biofilms and enhancing wound healing, which encounters a significant challenge of controlling the NO release behavior at the wound site. Herein, a kind of phenylalanine based poly(ester urea)s with high thermal stability are synthesized and fabricated to electrospun films as NO loading vehicle for infected wound treatment. The resultant films can continuously and stably release nitric oxide for 360 h with a total concentration of 1.15 μmol L −1 , which presents obvious advantages in killing the bacteria and removing biofilms. The results exhibit the films have no cytotoxicity and may accelerate the wound repair without causing inflammation, hemolysis, or cytotoxic reactions as well as stimulate the proliferation of fibroblasts and increase the synthesis of collagen. Therefore, the films may be a suitable NO releasing dressing for removing biofilms and repairing infected wounds.
研究领域:
材料科学
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生物医学工程
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伤口愈合
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2020
·Vol. 12
·期 37
·19293-19307
·
IF 6.895
Fangmei Zhang,Shikai Liu,Na Zhang,Ye Kuang,Wenting Li,Shili Gai,Fei He,Arif Gulzar,Piaoping Yang
Hypoxia in tumor cells is regarded as the most crucial cause of clinical drug resistance and radio-resistance; thus, relieving hypoxia of tumor cells is the key to enhancing the efficacy of anticancer therapy. As a gas signal molecule of vasodilatation factors, nitric oxide (NO) can relieve the hypoxia status of tumor cells, thereby, enhancing the sensitivity of tumor cells to radiotherapy. However, considering complications of vascular activity, the level of NO required for radiotherapy sensitization cannot be obtained in vivo. In view of this, we design and fabricate a multifunctional bismuth-based nanotheranostic agent, which is functionalized with S-nitrosothiol and termed Bi–SNO NPs. X-rays break down the S–N bond and simultaneously trigger large amount of NO-releasing (over 60 μM). Moreover, the as-prepared Bi–SNO NPs not only possess the capability of absorbing and converting 808 nm NIR photons into heat for photothermal therapy, but also have the ability to increase X-ray absorption and CT imaging sensitivity. In addition, the collaborative radio-, photothermal-, and gas-therapy of Bi–SNO in vivo was further investigated and remarkable synergistic tumor inhibition was realized. Finally, no obvious toxicity of Bi–SNO NPs was observed in the treated mice within 14 days. Therefore, the Bi–SNO developed in this work is an effective nano-agent for cancer theranostics with well-controlled morphology and uniform size (36 nm), which could serve as a versatile CT imaging-guided combined radio-, photothermal- and gas-therapy nanocomposite with negligible side effects.
研究领域:
癌症治疗
·
纳米技术
·
放射学
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诊疗一体化
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2021
·
IF 4.451
Xiaoyan Su,Ming Zhao,Xinyu Fu,Xiaodan Ma,Wei Xu,Songhua Hu
Polysaccharides from Rubus chingii Hu fruits (RFPs) were extracted, purified, characterized and investigated for immunomodulatory activity. Results indicated that RFPs were heteropolysaccharides with molecular weight of 51.7 kDa and contained carbohydrate contents of 96.83%. RFPs with characteristic absorptive peaks of polysaccharide structure and α-configuration were composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose and fucose with a molecular ratio of 0.08:0.17:0.16:0.48:5.73:1.00:1.79:0.03. RFPs promoted splenocyte proliferation, NO release, cytokine production and intracellular Ca 2+ concentration. The mechanism underlying splenocyte activation by RFPs was elucidated by RNA-Seq, in which 2214 differentially expressed genes (DEGs), 2030 GO terms and 92 KEGG pathways were identified. RFPs were further proved to induce a balanced Th1/Th2/Th17 response pattern through MAPK, NF-κB, Jak-STAT and Calcium signaling pathways in splenocytes. These findings provided a fundamental basis for the further application of RFPs as immunomodulators in food and medicine.
研究领域:
免疫学
·
药理学
·
分子生物学
·
生物化学
✓ 已验证
DOI
高影响因子
Materials Today Bio
·
2022
·
IF 10.761
Yi Feng,Hanxi Zhang,Xiaoxue Xie,Yu Chen,Geng Yang,Xiaodan Wei,Ningxi Li,Mengyue Li,Tingting Li,Xiang Qin,Shun Li,Fengming You,Chunhui Wu,Hong Yang,Yiyao Liu
Therapeutic approaches of combining conventional photodynamic therapy (PDT) with other adjuvant treatments to sensitize PDT represent an appealing strategy. Herein, a novel synergetic “nanobomb” strategy based on glutathione (GSH)-responsive biodegradation was proposed to effectively destroy tumors expeditiously and accurately. This “nanobomb” was rationally constructed via the simultaneous encapsulation of methylene blue (MB) and l -arginine (L-Arg) into polyethylene glycol (PEG) modified mesoporous organosilicon nanoparticles (MON). The resulting L-Arg/ [email protected] initially exhibited prolonged blood circulation, improved bioavailability, and enhanced tumor accumulation in mice after tail vein injection according to the pharmacokinetic investigations, before the nanoparticles were entirely excreted. Under laser irradiation, L-Arg/ [email protected] produced remarkable reactive oxygen species (ROS) directly for PDT therapy, while a portion of ROS may oxidize L-Arg to generate nitric oxide (NO) not only for gas therapy (GT) but also serve as a biological messenger to regulate vasodilation to alleviate the tumor hypoxia. Subsequently, the rapidly released NO was further oxidized to reactive nitrogen species, which together with ROS promote immunogenic cell death by inducing G2/M cell-cycle arrest and apoptosis in cancer cells, and eventually resulting in enhanced anti-tumor immune responses. Moreover, the GSH depletion in tumor tissues induced by L-Arg/ [email protected] biodegradation can cooperate with GT to amplify the therapeutic effect of PDT. These results demonstrate that this “nanobomb” provides new ideas for clinical translation to treat tumor patients in terms of synergistic PDT-GT nanotherapy in hypoxic-solid tumors.
研究领域:
癌症治疗
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）