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Chinese Chemical Letters 2024年第8期35卷 128-137页

作者： Ningyue Xu Jun Wang Lei Liu changyang gong Division of Head&Neck Tumor Multimodality Treatment Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Radiotherapy(RT)is a crucial treatment for cancer;however,its effectiveness is limited by adverse effects on normal tissues,radioresistance,and tumor *** overcome these challenges,hydrogels have been employed for delivery of radiosensitizers and other therapeutic *** review summarizes recent advancements in the application of hydrogel-based local drug delivery systems for improving the therapeutic efficacy of RT in cancer ***,we introduce the classification and properties of ***,we detail hydrogel-based platforms designed to enhance both external beam radiation therapy and *** also discuss hydrogels used in combination therapy involving RT and ***,we highlight the challenges that hydrogels face in *** surveying the latest developments in hydrogel applications for RT,this review aims to provide insights into the development of more effective and targeted cancer therapies.

关键词： Radiotherapy Drug delivery systems Hydrogel Radiation sensitization Combination therapy

Recent advances in enhancing reactive oxygen species based chemodynamic therapy

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Chinese Chemical Letters 2022年第5期33卷 2213-2230页

作者： Xinchao Li Rui Luo Xiuqi Liang Qinjie Wu changyang gong State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan UniversityChengdu 610041China

Chemodynamic therapy(CDT),defined as an in situ oxidative stress response catalyzed by the Fenton or Fenton-like reactions to generate cytotoxic hydroxyl radicals(•OH)at tumor sites,exhibits conspicuous inhibition of tumor *** has attracted extensive attention for its outstanding edge in effectiveness,lower systemic toxicity and side effects,sustainability,low cost and ***,the inconfor-mity of harsh Fenton reaction conditions and tumor microenvironment hamper its further development,based on which,numerous researchers have made efforts in further improving the efficiency of *** this review,we expounded antitumor capacity of CDT in mechanism,together with its limitation,and then summarized and came up with several strategies to enhance CDT involved tumor therapy strategies by 1)improving catalytic efficiency;2)increasing hydrogen peroxide levels at tumor sites;3)reducing glutathione levels at tumor sites;4)applying external energy intervention;5)amplifying the distribu-tion of hydroxyl radicals at tumor sites;and 6)combination ***,the perspectives and challenges of CDT are further discussed to encourage more in-depth studies and rational reflections.

关键词： Chemdynamic therapy Fenton or fenton-like reactions Reactive oxygen species Increasing hydrogen peroxide levels Reducing glutathione levels External energy intervention Combination therapy

Nanomaterials for radiotherapeutics-based multimodal synergistic cancer therapy

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Nano Research 2020年第10期13卷 2579-2594页

作者： Xi Yang Ling Gao Qing Guo Yongjiang Li Yue Ma Ju Yang changyang gong Cheng Yi Department of Medical Oncology Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China Department of Oncology Taizhou Peoples HospitalTaizhou 225300China Department of Pathophysiology West China School of Basic Medical Sciences and Forensic MedicineSichuan UniversityChengdu 610041China

Over the past decade,numerous studies have attempted to enhance the effectiveness of radiotherapy(external beam radiotherapy and internal radioisotope therapy)for cancer ***,the low radiation absorption coefficient and radiation resistance of tumors remain major critical challenges for radiotherapy in the *** the development of nanomedicine,nanomaterials in combination with radiotherapy offer the possibility to improve the efficiency of radiotherapy in *** act not only as radiosensitizers to enhance radiation energy,but also as nanocarriers to deliver therapeutic units in combating radiation *** this review,we discuss opportunities for a synergistic cancer therapy by combining radiotherapy based on nanomaterials designed for chemotherapy,photodynamic therapy,photothermal therapy,gas therapy,genetic therapy,and *** highlight how nanomaterials can be utilized to amplify antitumor radiation responses and describe cooperative enhancement interactions among these synergistic ***,the potential challenges and future prospects of radio-based nanomedicine to maximize their synergistic efficiency for cancer treatment are identified.

关键词： cancer treatment radiotherapy synergistic therapies nanomaterials

Self-sufficient nanoparticles with dual-enzyme activity trigger radical storms and activate cascade-amplified antitumor immunologic responses

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Acta Pharmaceutica Sinica B 2024年第2期14卷 821-835页

作者： Liping Bai Jin Yang Siting Yu Zhongzheng Xiang Yuanyuan Zeng Meiling Shen Xiaorong Kou Qinjie Wu changyang gong Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Radiotherapy(RT) can potentially induce systemic immune responses by initiating immunogenic cell death(ICD) of tumor ***,RT-induced antitumor immunologic responses are sporadic and insufficient against cancer ***,we construct multifunctional self-sufficient nanoparticles(MARS) with dual-enzyme activity(GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic *** addition to limiting the Warburg effect to actualize starvation therapy,MARS catalyzes glucose to produce hydrogen peroxide(H_(2)O_(2)),which is then used in the Cu^(+)-mediated Fenton-like reaction and RT *** and chemodynamic therapy produce reactive oxygen species in the form of radical storms,which have a robust ICD impact on mobilizing the immune ***,when MARS is combined with RT,potent systemic antitumor immunity can be generated by activating antigen-presenting cells,promoting dendritic cells maturation,increasing the infiltration of cytotoxic T lymphocytes,and reprogramming the immuno suppre ssive tumor ***,the synergistic therapy of RT and MARS effectively suppresses local tumor growth,increases mouse longevity,and results in a 90% reduction in lung metastasis and postoperative ***,we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.

关键词： Dual-enzyme activity Radiotherapy Chemodynamic therapy Fenton-likereaction Radical storms Immunogeniccell death Tumormicroenvironment Systemicimmunity

Gambogic acid-encapsulated polymeric micelles improved therapeutic effects on pancreatic cancer

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Chinese Chemical Letters 2019年第4期30卷 885-888页

作者： Yan Wang Xinxin Wang Jing Zhang Li Wang Chunqing Ou Yaqian Shu Qinjie Wu Guolin Ma changyang gong State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Department of Radiology China-Japan Friend Hospital

Gambogic acid(GA) is a natural product with potent anticancer activity in vitro. However, poor water solubility and systematic toxicity limit the further clinical application of GA. Micellization of hydrophobic molecule could effectively ameliorate aqueous dispersity of GA and induce better blood retention and tumor accumulation, hence lead to improved stability and therapeutic effect of GA. In this study, monomethyl poly(ethylene glycol)-poly(ε-caprolactone)-poly(trimethylene carbonate)(MPEG-P(CL-ran-TMC)) was used to encapsulate GA by a single-step solid dispersion method to form a GA encapsulated MPEG-P(CLran-TMC) micelles(GA micelles). GA micelles were characterized with a small particle size(44 ±1 nm),high drug loading content(26.28% ± 0.12%) and high-efficiency encapsulation(87.59% ± 0.41 %). Compared with free GA, GA micelles showed better dispersion in water, prolonged release behavior in vitro, and enhanced tumor cellular uptake. GA micelles could also effectively induce apoptosis in AsPC-1 *** with free GA, GA micelles exhibited superior antitumor efficacy and better apoptosis induced effect in a subcutaneous xenograft mouse model of AsPC-1 cells. In conclusion, GA micelles which showed high-efficiency anti-tumor effect in vitro and in vivo may serve as a candidate for pancreatic cancer therapy.

关键词： Gambogic acid Pancreatic cancer Polymeric micelles Drug delivery Cancer therapy

A tactical nanomissile mobilizing antitumor immunity enables neoadjuvant chemo-immunotherapy to minimize postsurgical tumor metastasis and recurrence

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Acta Pharmaceutica Sinica B 2023年第2期13卷 804-818页

作者： Tao He Mingxing Hu Shunyao Zhu Meiling Shen Xiaorong Kou Xiuqi Liang Lu Li Xinchao Li Miaomiao Zhang Qinjie Wu changyang gong State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan UniversityChengdu 610041China

Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers,which benefits from tumor ***,the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and ***,a tactical nanomissile(TALE),equipped with a guidance system(PD-L1 monoclonal antibody),ammunition(mitoxantrone,Mit),and projectile bodies(tertiary amines modified azobenzene derivatives),is designed as a neoadjuvant chemo-immunotherapy setting,which aims at targeting tumor cells,and fast-releasing Mit owing to the intracellular azoreductase,thereby inducing immunogenic tumor cells death,and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune *** formed in situ tumor vaccine can recruit and activate antigen-presenting cells,and ultimately increase the infiltration of CD8^(+)T cells while reversing the immunosuppression ***,this approach provokes a robust systemic immune response and immunological memory,as evidenced by preventing 83.3%of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse ***,our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.

关键词： Neoadjuvant Chemotherapy Immunotherapy Mitoxantrone Vaccine Azobenzene derivatives Reduction responsive Melanoma

Programmable double-unlock nanocomplex self-supplies phenylalanine ammonia-lyase for precise phenylalanine deprivation of tumors

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Chinese Chemical Letters 2024年第8期35卷 455-459页

作者： Chunqing Ou Meijia Xiao Xinyue Zheng Xianzhou Huang Suleixin Yang Yingying Leng Xiaowei Liu Xiuqi Liang Linjiang Song Yanjie You Shaohua Yao changyang gong Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoAvenida da UniversidadeTaipaMacao 999087China School of Medical and Life Sciences Chengdu University of Traditional Chinese MedicineChengdu 611137China Department of Gastroenterology People’s Hospital of Ningxia Hui Autonomous RegionYinchuan 750002China

Essential amino acids(EAAs)deprivation is a potential antitumor approach because EAAs are critical for tumor *** efficiently inhibit tumor growth,continuous deprivation of EAAs is required,how-ever,continuous deprivation without precise control will introduce toxicity to normal ***,a programmable double-unlock nanocomplex(ROCK)was prepared,which could self-supply phenylalanine ammonia-lyase(PAL)to tumor cells for phenylalanine(Phe)*** was double-locked in physiological conditions when administered *** ROCK actively targeted to tumor cells by integrinαvβ3/5 and CD44,ROCK was firstly unlocked by cleavage of protease on tumor cell membrane,exposing CendR and R8 to enhance ***,hyaluronic acid was digested by hyaluronidase overexpressed in endo/lysosome of tumor cells,in which ROCK was secondly unlocked,resulting in pro-moting endo/lysosome escape and PAL plasmid(pPAL)*** pPAL could sustainably express PAL in host tumor cells until the self-supplied PAL precisely and successfully deprived Phe,thereby block-ing the protein synthesis and killing tumor cells ***,our precise Phe deprivation strategy effectively inhibited tumor growth with no observable toxicity to normal cells,providing new insights to efficiently remove intratumoral nutrition for cancer therapy.

关键词： Programmable double-unlock Essential amino acids deprivation Phenylalanine ammonia-lyase Self-supply Gene therapy

Reversing cancer immunoediting phases with a tumor-activated and optically reinforced immunoscaffold

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Bioactive Materials 2024年第5期35卷 228-241页

作者： Xinchao Li Xiuqi Liang Wangxian Fu Rui Luo Miaomiao Zhang Xiaorong Kou Yi Zhang Yingjie Li Dongxue Huang Yanjie You Qinjie Wu changyang gong Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China Department of Anesthesiology Shengjing Hospital of China Medical UniversityShenyang110022China Department of Gastroenterology People’s Hospital of Ningxia Hui Autonomous RegionYinchuan750002China

In situ vaccine(ISV)is a promising immunotherapeutic tactic due to its complete tumoral antigenic ***,its efficiency is limited by extrinsic inevitable immunosuppression and intrinsic immunogenicity *** break this plight,a tumor-activated and optically reinforced immunoscaffold(TURN)is exploited to trigger cancer immunoediting phases regression,thus levering potent systemic antitumor immune *** response to tumoral reactive oxygen species,TURN will first release RGX-104 to attenuate excessive immunosuppressive cells and cytokines,and thus immunosuppression falls and immunogenicity ***,intermittent laser irradiation-activated photothermal agents(PL)trigger abundant tumor antigens exposure,which causes immunogenicity springs and preliminary infiltration of T ***,CD137 agonists from TURN further promotes the proliferation,function,and survival of T cells for durable antitumor ***,cancer immunoediting phases reverse and systemic antitumor immune responses *** achieves over 90%tumor growth inhibition in both primary and secondary tumor lesions,induces potent systemic immune responses,and triggers superior long-term immune memory in *** together,TURN provides a prospective sight for ISV from the perspective of immunoediting phases.

关键词： Hydrogel Immunoscaffold In situ vaccine Photothermal therapy Immunoediting phases

一种可生物降解温度敏感型聚乙二醇-聚己内酯-聚乙二醇水凝胶的合成和表征

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生物医学工程学杂志 2008年第5期25卷 1121-1125页

作者：巩长旸顾迎春谢震谢希惠刘彩兵阚兵涂铭旌魏于全钱志勇四川大学华西医院肿瘤生物治疗国家重点实验室成都610041 四川大学纺织系成都610065 江苏省姜堰市中医院姜堰225500 四川大学材料科学与工程学院成都610065

合成了一系列分子量较低的聚乙二醇-聚己内酯-聚乙二醇(Poly(ethylene glycol)-Polycaprolactone-Poly(ethylene glycol),PEG-PCL-PEG)三嵌段共聚物。分别采用FTIR和1H-NMR对其结构进行了表征。所合成的PEG-PCL-PEG共聚物具有良好的水溶性,当水溶液浓度高于临界凝胶浓度(Critical gel concentration,CGC)时,随着温度的变化聚合物水溶液会呈现特有的凝胶-溶胶转变。研究了共聚物亲水疏水链段的比例和长度,以及热历史等对凝胶-溶胶转变行为的影响。通过调节上述条件,可以在一定程度上拓宽凝胶-溶胶转变温度范围,有助于PEG-PCL-PEG水凝胶在可注射药物控制释放系统等方面的应用。

关键词：聚己内酯-聚乙二醇共聚物可生物降解温度敏感水凝胶

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油库火灾爆炸事故致因与网络演化研究

安全与环境学报 2024年第12期24卷 4591-4597页

作者：龚晓凤宋长洋付明福张杰国家管网集团西部管道公司乌鲁木齐830011 中国石油大学(北京)安全与海洋工程学院北京102249

当前油气储运行业面临隐患排查未成体系、风险管控缺乏量化手段等突出问题,在此背景下,基于复杂网络相关理论与方法,以油气储运行业中较为典型的油库火灾爆炸历史事故案例为研究对象,对其事故致因与网络演化过程进行研究。在建立事故致... 详细信息

当前油气储运行业面临隐患排查未成体系、风险管控缺乏量化手段等突出问题,在此背景下,基于复杂网络相关理论与方法,以油气储运行业中较为典型的油库火灾爆炸历史事故案例为研究对象,对其事故致因与网络演化过程进行研究。在建立事故致因网络的基础上,以油库火灾爆炸历史事故中导致事故发生的风险因素及最终后果作为该网络模型的节点,从中分析并提取事故链,同时将事故发生次数作为节点之间连边的权重,以此建立事故有向加权致因网络模型。最后,选取部分重要的拓扑特性指标结合熵值法对该网络进行量化分析,找出事故演化的关键风险点。同时通过平均最短路径长度与网络直径的分析,发现该网络具有较小的平均最短路径长度,各个风险因素关联紧密,具有小世界特性。通过研究油库火灾爆炸事故网络重要节点与风险传播速度,可以更好地理解油库火灾爆炸事故发生的机理和规律,为风险管理提供参考。

关键词：安全工程油库火灾爆炸复杂网络事故演化网络拓扑

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