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H_(2)O_(2)-sensitive nanoscale coordination polymers for photoacoustic tumors imaging via in vivo chromogenic assay

Journal of Innovative Optical Health Sciences 2022年第5期15卷 1-12页

作者： Jiayue Zhao Fei Gong Nailin Yang huali lei Zhihui Han Yuqi Yang Liang Cheng Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices Institute of FunctionalNano&Soft Materials(FUNSOM)Soochow University Suzhou 215123 JiangsuP.R.China Wuhan National Laboratory for Optoelectronics and School of Optical and Electronic Information Huazhong University of Science and Technology Wuhan 430074 P.R.China

Photoacoustic(PA)imaging with much deeper tissue penetration and better spatial resolution had been widely employed for the prevention and diagnosis of many *** this study,a new type of hydrogen peroxide(H_(2)O_(2)T-activated photoacoustic nanoprobe[Mn-AH nanoscale coordination polymer nanodots(NCPs)]was successfully synthesized by a simple one-step method in water phase containing 2,20-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),horse radish peroxidase(HRP),and manganese ion(Mn^(2+).After modification by polyethylene glycol(PEG),Mn-AH NCPs exhibited excellent stability and biocompatibility for in vivo H_(2)O_(2)-responsive chromogenic assay with great speci¯city and *** the presence of H_(2)O_(2),colorless ABTS would be converted by HRP into the oxidized form with strong near-infrared(NIR)absorbance,enabling photoacoustic detection of endogenous H_(2)O_(2).Using H_(2)O_(2)-activated Mn-AH NCPs,we have successfully performed PA imaging and H_(2)O_(2)detection of subcutaneous murine colon CT26 tumor and deep-seated orthotopic bladder *** to the inherent Mn element existence inside the Mn-AH,this nanoprobe also serves as a good T1-weighted magnetic resonance imaging(MRI)contrast agent ***,after accomplishing its imaging functions,the Mn-AH NCPs could be cleared out from the body without any long-term toxicity,providing a new opportunity for cancer diagnosis and treatment.

关键词： Nanoscale coordination polymers(NCPs) PA imaging MRI H2O2 detection metabolic nanoprobes

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Biodegradable magnesium alloy with eddy thermal effect for effective and accurate magnetic hyperthermia ablation of tumors

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National Science Review 2021年第1期8卷 98-108页

作者： Nailin Yang Fei Gong Liang Cheng huali lei Wei Li Zongbin Sun Caifang Ni Zhanhui Wang Zhuang Liu Institute of Functional Nano & Soft Materials (FUNSOM) Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices Soochow University Department of Vascular Surgery and Interventional Radiology First Affiliated Hospital of Soochow University Luoyang Central Hospital affiliated to Zhengzhou University

Magnetic hyperthermia therapy (MHT) is able to ablate tumors using an alternating magnetic field (AMF)to heat up magnetocaloric agents (e.g. magnetic nanoparticles) administered into the tumors. For clinical applications, there is still a demand to find new magnetocaloric agents with strong AMF-induced heating performance and excellent biocompatibility. As a kind of biocompatible and biodegradable material,magnesium (Mg) and its alloys have been extensively used in the clinic as an implant metal. Herein, we discovered that the eddy thermal effect of the magnesium alloy (MgA) could be employed for MHT to effectively ablate tumors. Under low-field-intensity AMFs, Mg A rods could be rapidly heated, resulting in a temperature increase in nearby tissues. Such AMF-induced eddy thermal heating of MgA could not only be used to kill tumor cells in vitro, but also be employed for effective and accurate ablation of tumors in vivo. In addition to killing tumors in mice, we further demonstrated that VXtumors of much larger sizes growing in rabbits after implantation of Mg A rods could also be eliminated after exposure to an AMF, illustrating the ability of MgA-based MHT to kill large-sized tumors. Moreover, the implanted MgA rods showed excellent biocompatibility and～20%of their mass was degraded within three months. Our work thus discovered for the first time that non-magnetic biodegradable Mg A, an extensively used implant metal in clinic, could be used for effective magnetic thermal ablation of tumors under a low-field-intensity AMF. Such a strategy could be readily translated into clinical use.

关键词： magnesium alloy eddy thermal effect alternating magnetic field hyperthermia tumor ablation biodegradation

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An anti-inflammatory and neuroprotective biomimetic nanoplatform for repairing spinal cord injury

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Bioactive Materials 2022年第12期7卷 569-582页

作者： Xiang Gao Zhihui Han Cheng Huang huali lei Guangqiang Li Lin Chen Dandan Feng Zijie Zhou Qin Shi Liang Cheng Xiaozhong Zhou Department of Orthopedics The Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu215004China Institute of Functional Nano&Soft Materials(FUNSOM) Collaborative Innovation Center of Suzhou Nano Science and TechnologySoochow UniversitySuzhouJiangsu215123China Department of Orthopedics The First Affiliated Hospital of Soochow UniversityOrthopedic InstituteSoochow University188 Shizi Road215006SuzhouJiangsuChina

Spinal cord regeneration after a spinal cord injury (SCI) remains a difficult challenge due to the complicated inflammatory microenvironment and neuronal damage at the injury sites. In this study, retinoic acid (RA) and curcumin (Cur) were co-loaded with bovine serum albumin (BSA) self-assembly to obtain RA@BSA@Cur nanoparticles (NPs) for SCI treatment. Cur, as an antioxidant drug, facilitated reactive oxygen species (ROS) scavenging, and decreased the amount of inflammatory factors secreted by macrophages, while RA could enhance neurite extensions and neural differentiation. The constructed RA@BSA@Cur NPs not only induced polarization of macrophages toward pro-regenerative phenotypes and markedly reduced the inflammatory response of macrophages or microglia, but also increased neurite length in PC12 cells and neuronal differentiation of bone marrow mesenchymal stem cells, improved the differentiation of neural stem cells (NSCs) into β3- tubulin+ neurons, and reversed the pro-astrocyte differentiation effect of inflammatory cytokines on NSCs. In vivo experiments revealed that RA@BSA@Cur NPs regulated the phenotypic polarization of macrophages, inhibited the release of inflammatory mediators, promoted functional neuron regeneration and motor function, and further inhibited scar tissue formation. This study highlighted that the BSA-based biomimetic nanomaterials could be used as ROS scavengers and nerve regeneration promoters for treating SCI.

关键词： Biomimetic nanomaterials ROS scavenging Anti-inflammatory Spinal cord injury Neuro-protective

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Titanium carbide nanosheets with defect structure for photothermal-enhanced sonodynamic therapy

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Bioactive Materials 2022年第2期7卷 409-419页

作者： Guangqiang Li Xiaoyan Zhong Xianwen Wang Fei Gong huali lei Yangkai Zhou Chengfei Li Zhidong Xiao Guoxi Ren Liang Zhang Zhiqiang Dong Zhuang Liu Liang Cheng College of Science State Key Laboratory of Agricultural MicrobiologyHuazhong Agricultural UniversityWuhan430070China Institute of Functional Nano&Soft Materials(FUNSOM) Jiangsu Key Laboratory for Carbon-Based Functional Materials&DevicesSoochow UniversitySuzhou215123China Department of Toxicology School of Public HealthMedical College of Soochow UniversitySuzhou215123China State Key Laboratory of Functional Materials for Informatics Shanghai Institute of Microsystem and Information TechnologyChinese Academy of SciencesShanghai200050China College of Biomedicine and Health College of Life Science and TechnologyHuazhong Agricultural UniversityWuhanHubei430070China

Sonodynamic therapy(SDT)has attracted widespread interest in biomedicine,owing to its novel and noninvasive therapeutic method triggered by ultrasound(US).Herein,the Ti_(3)C_(2) MXene nanosheets(Ti_(3)C_(2) NSs)are developed as good sonosensitizers via a two-step method of chemical exfoliation and high-temperature *** the high-temperature treatment,the oxygen defect of Ti_(3)C_(2) MXene nanosheets(H-Ti_(3)C_(2) NSs)is greatly ***,the electron(e^(-))and hole(h^(+))generated by US can be separated faster due to the improved degree of oxidation,and then the recombination of e^(-)-h^(+)can be prevented with the abundant oxygen defect under US irradiation,which induced the sonodynamic efficiency greatly to improve around 3.7-fold compared with Ti_(3)C_(2) NSs without high-temperature *** PEGylation,the H-Ti_(3)C_(2)-PEG NSs show good stability and *** vitro studies exhibit that the inherent property of mild photothermal effect can promote the endocytosis of H-Ti_(3)C_(2)-PEG NSs,which can improve the SDT *** vivo studies further display that the increased blood supply by the mild photothermal effect can significantly relieve hypoxia in the tumor microenvironment,showing photothermal therapy(PTT)enhanced *** importantly,the H-Ti_(3)C_(2)-PEG NSs can be biodegraded and excreted out of the body,showing no significant long-term *** work develops the defective H-Ti_(3)C_(2) NSs as high-efficiency and safe sonosensitizers for photothermal-enhanced SDT of cancer,extending the biomedical application of MXene-based nanoplatforms.

关键词： Ti_(3)C_(2)MXenes Oxygen defect Sonosensitizers Sonodynamic therapy Biosafety

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Manganese molybdate nanodots with dual amplification of STING activation for“cycle”treatment of metalloimmunotherapy

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Bioactive Materials 2024年第1期31卷 53-62页

作者： huali lei Quguang Li Guangqiang Li Tianyi Wang Xinjing Lv Zifan Pei Xiang Gao Nailin Yang Fei Gong Yuqi Yang Guanghui Hou Minjiang Chen Jiansong Ji Zhuang Liu Liang Cheng Institute of Functional Nano&Soft Materials(FUNSOM) Jiangsu Key Laboratory for Carbon-Based Functional Materials and DevicesSoochow UniversitySuzhou215123China Department of Neurosurgery The First Affiliated Hospital of Soochow UniversitySuzhou215000China Children’s Hospital of Soochow University Pediatric Research Institute of Soochow UniversitySuzhou215123China Department of Orthopedics The Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu215004China Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research Fifth Affiliated Hospital of Wenzhou Medical UniversityLishui323000ZhejiangChina

Certain types of cationic metal ions,such as Mn^(2+)are able to activate immune functions via the stimulator of interferon genes(STING)pathway,showing potential applications in eliciting antitumor *** anionic ions interact with immune cells remains largely ***,selecting from a range of cationic and anionic ions,we were excited to discover that MoO_(4)^(2-)could act as a cGAS-STING agonist and further confirmed the capability of Mn^(2+)to activate the cGAS-STING *** by such findings,we synthesized manganese molybdate nanoparticles with polyethylene glycol modification(MMP NDs)for cancer ***,MMP NDs could consume glutathione(GSH)over-expressed in tumors and induce ferroptosis owing to high-valence Mo and Mn to elicit tumor-specific immune responses,which was further amplified by MMP-triggered the cGAS-STING *** turn,activated CD8+T cells to secrete high levels of interferonγ(IFN-γ)and reduced GPX4 expression in tumor cells to trigger ferroptosis-specific lipid peroxidation,which constituted a“cycle”of *** a result,the metalloimmunotherapy with systemic administration of MMP NDs offered a remarkable tumor inhibition effect for a variety of tumor *** work for the first time discovered the ability of anionic metal ions to activate the immune system and rationally designed bimetallic oxide nanostructures as a multifunctional therapeutic nanoplatform for tumor immunotherapy.

关键词： Metalloimmunotherapy Manganese molybdate nanoparticles cGAS-STING pathway DCs maturation Ferroptosis

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Tumor microenvironment-responsive contrast agents for specific cancer imaging:a narrative review

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Journal of Bio-X Research 2020年第4期3卷 144-156页

作者： Xianwen Wang Xiaoyan Zhong huali lei Nailin Yang Xiang Gao Liang Cheng Institute of Functional Nano&Soft Materials(FUNSOM) Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices Department of Toxicology School of Public HealthJiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric DiseasesMedical College The Second Affiliated Hospital of Soochow University SuzhouJiangsu ProvinceChina

Molecular imaging is of great significance for early diagnosis and timely treatment of cancer and disease,as well as basic medical and biological *** personalized cancer treatment has become increasingly popular,the demand for more advanced imaging technologies has also significantly *** advantage of differences between the tumor microenvironment and normal tissue cells,tumor microenvironment-responsive or"turn-on"contrast agents have a higher signal-to-noise ratio and lower background interference compared with"turn-off"probes,which can remarkably improve the performance of tumor ***,tumor microenvironment-responsive contrast agents can not only detect changes in the tumor microenvironment,but also have important significance for tumor diagnosis,prediction of invasion potential,evaluation of treatment effectiveness,planning of therapeutic regimens,and tumor ***,this review focuses on recent research progress of tumor microenvironment-responsive intelligent probes,and highlights future research directions of tumor microenvironment-responsive contrast agents for precision diagnostics.

关键词： cancer imaging cancer treatment contrast agents diagnosis tumor microenvironment

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我国机会性致病真菌的耐药现状

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国际流行病学传染病学杂志 2016年第6期43卷 412-415页

作者：李凌华雷华丽唐小平广州市第八人民医院感染科 510060 广州市第八人民医院传染病研究所 510060

近年来，由于免疫缺陷疾病的增多及侵入性医疗操作的发展，我国机会性致病真菌感染的发病率和死亡率不断增加。由于临床不规范使用甚至滥用抗真菌药物，机会性真菌的治疗面临耐药的重大挑战。此文就近年来临床常见的机会性致病真菌，如... 详细信息

近年来，由于免疫缺陷疾病的增多及侵入性医疗操作的发展，我国机会性致病真菌感染的发病率和死亡率不断增加。由于临床不规范使用甚至滥用抗真菌药物，机会性真菌的治疗面临耐药的重大挑战。此文就近年来临床常见的机会性致病真菌，如念珠菌属、曲霉菌属、隐球菌属、踝节菌属及毛霉菌属的耐药现状进行综述，为临床治疗提供参考。

关键词：真菌耐药抗真菌药物

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机会性致病真菌耐药机制的研究进展

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国际流行病学传染病学杂志 2017年第4期44卷 270-273页

作者：雷华丽唐小平李凌华广州医科大学附属广州市第八人民医院传染病研究所 510060 广州医科大学附属广州市第八人民医院感染科 510060

随着免疫缺陷疾病的增多及器官移植等医疗技术的发展，机会性致病真菌感染的发病率和死亡率日渐升高。同时，由于临床上抗真菌药物的不规范使用，机会性真菌的耐药问题日渐凸显。近年来对机会性真菌耐药机制的研究成为热点，其中包括药... 详细信息

随着免疫缺陷疾病的增多及器官移植等医疗技术的发展，机会性致病真菌感染的发病率和死亡率日渐升高。同时，由于临床上抗真菌药物的不规范使用，机会性真菌的耐药问题日渐凸显。近年来对机会性真菌耐药机制的研究成为热点，其中包括药物外排的增加、药物作用靶点的改变、生物被膜的形成等，本文对以上内容进行综述。

关键词：机会致病菌感染抗真菌药物耐药

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血浆可溶性CD14在HIV-1感染者HAART中的变化和意义

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中国艾滋病性病 2017年第7期23卷 599-602,612页

作者：何耀祖李凌华雷华丽胡凤玉李永红蔡卫平唐小平中山大学附属第三医院广州510630 广州市第八人民医院广州510060

目的观察血浆可溶性白细胞分化抗原14(sCD14)在艾滋病病毒1型(HIV-1)感染者联合高效抗反转录病毒治疗(HAART)过程中表达水平的变化,探讨HAART过程中血浆sCD14的变化规律及意义。方法以26例HIV-1感染者为研究对象,20名健康献血者为对照... 详细信息

目的观察血浆可溶性白细胞分化抗原14(sCD14)在艾滋病病毒1型(HIV-1)感染者联合高效抗反转录病毒治疗(HAART)过程中表达水平的变化,探讨HAART过程中血浆sCD14的变化规律及意义。方法以26例HIV-1感染者为研究对象,20名健康献血者为对照。用酶联免疫吸附试验(ELISA)检测健康对照组和HIV-1感染者HAART前(基线)和治疗后12、24、36及48周的血浆sCD14水平,分析sCD14表达水平变化及其与病毒学、免疫学应答的关系。结果 26例HIV-1感染者与20例对照组年龄及性别比较差异无统计学意义(t=1.813,P=0.07;χ~2=0.001,P=0.971)。HIV-1感染组基线血浆sCD14水平为(4.72±2.84)×10~6pg/mL,明显高于对照组(0.59±0.32)×10~6pg/mL(t=6.468,P<0.001),且治疗后呈明显下降趋势(F=25.975,P<0.001)。HIV-1感染组血浆sCD14在治疗12周时达(5.92±5.27)×10~6 pg/mL,与基线比较差异无统计学意义(t=1.026,P=0.315);治疗24周后迅速下降至(0.44±0.35)×10~6pg/mL,明显低于基线(t=-7.630,P<0.001),并接近对照组水平(t=1.436,P=0.158);随后血浆sCD14维持低水平,36周及48周时分别为(0.52±0.25)×10~6 pg/mL和(0.60±0.36)×10~6pg/mL,与24周及对照组比较差异均无统计学意义(t=0.825,P=0.417;t=1.558,P=0.132;t=0.863,P=0.393;t=1.80,P=0.858)。治疗24周血浆sCD14变化与Th/Ts比值变化呈负相关(r=-0.477,P=0.013),48周时血浆sCD14变化与HIV-1RNA变化呈正相关(r=0.428,P=0.029)。结论血浆sCD14在HIV-1感染者中上升,经过有效HAART后下降,有望成为HAART疗效判断的指标。

关键词：艾滋病病毒1型微生物易位血浆可溶性白细胞分化抗原14 联合高效抗反转录病毒治疗

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血清Mplp抗原检测对艾滋病合并马尔尼菲蓝状菌病的诊断价值

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中华传染病杂志 2017年第3期35卷 157-160页

作者：李凌华肖赛银何艳胡凤玉陈万山雷华丽唐小平蔡卫平广州市第八人民医院感染科 510060 江门市中心医院

目的探讨马尔尼菲蓝状菌特异性甘露糖蛋白Mplp抗原检测在诊断艾滋病合并马尔尼菲蓝状菌病中的应用价值。方法2012年1月至2015年6月广州市第八人民医院收治的艾滋病合并马尔尼菲蓝状菌病患者184例，经病原学检测均马尔尼菲蓝状菌阳性；... 详细信息

目的探讨马尔尼菲蓝状菌特异性甘露糖蛋白Mplp抗原检测在诊断艾滋病合并马尔尼菲蓝状菌病中的应用价值。方法2012年1月至2015年6月广州市第八人民医院收治的艾滋病合并马尔尼菲蓝状菌病患者184例，经病原学检测均马尔尼菲蓝状菌阳性；对照组205例包括艾滋病未合并马尔尼菲蓝状菌病患者176例和健康对照者29名。使用双抗体夹心ELISA法和荧光免疫层析技术结合双抗体夹心法检测血清Mplp抗原，分析其对诊断艾滋病合并马尔尼菲蓝状菌病的灵敏度与特异度。统计学处理采用Х^2检验和t检验。结果艾滋病合并马尔尼菲蓝状菌病患者与对照组性别和年龄比较差异无统计学意义（Х^2=0．019，P—o．889；t=1．810，P=0．07）。双抗体夹心ELISA法和荧光免疫层析技术结合双抗体夹心法诊断艾滋病合并马尔尼菲蓝状菌病的灵敏度分别为82．07％（151／184）和83．15％（153／184），两种方法比较差异无统计学意义（Х^2=0．076，P=0．783）；特异度分别为93．17％（191／205）和92．68％（190／205），两种方法比较差异无统计学意义（Х^2=0．037，P=0．847）；准确度分别为87．92％（342／389）和88．17％（343／389），两种方法比较差异无统计学意义（Х^2=0．012，P=0．912）；假阳性率分别为6．83％（14／205）和7．32％（15／205），假阴性率分别为17．93％（33／184）和16．85％（31／184），两种方法比较差异无统计学意义（Х^2=0．049，P=0．829）；阳性预测值分别为91．52％（151／165）和91．07％（153／168），两种方法比较差异无统计学意义（Х^2=0．021，P=0．886）；阴性预测值分别为85．27％（191／224）和85．97％（190／221），两种方法比较差异无统计学意义（Х^2=0．045，P=0．832）；Kappa值分别为0．83和0．80。结论血清马尔尼菲蓝状菌Mplp抗原检测的特异度和敏感度较高，可用于早期快速诊断艾滋病合并马尔尼菲蓝状菌病。

关键词：获得性免疫缺陷综合征马尔尼菲蓝状菌甘露糖蛋白Mplp 血清学诊断

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