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Drug delivery systems for colorectal cancer chemotherapy

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Chinese Chemical Letters 2024年第2期35卷 163-175页

作者： Wen Chen Kun Shi Yan Yu Peipei Yang Zhongwu Bei Dong Mo Liping Yuan Meng Pan Yu Chen Zhiyong Qian department of biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Colorectal cancer causes the third most common type of malignant tumors with high morbidity and *** is currently one of the most effective and common treatments for colorectal ***,the poor water solubility of some chemotherapeutics,untargeted drug delivery,and the undesirable systemic side effects of conventional treatment remain the major issues for colorectal cancer ***,drug delivery systems(DDS)based on biomaterials have been widely investigated and found to be capable of resolving those issues with good ***,the main goal of this review is to summarize and discuss the progress and potential advantages of different DDS for colorectal cancer *** not only reviewed the nanocarriers used to improve the solubility of chemotherapeutics,including liposomes,micelles,and nanoparticles,but also discussed targeted DDS based on specific ligand-receptor recognition and tumor microenvironmental stimulus ***,locally administered systems based on hydrogels and microspheres,which have been shown to increase drug accumulation at the tumor site while decreasing systemic toxicity,were also *** provides a good option for improving the efficacy of chemotherapy in the treatment of colorectal cancer.

关键词： Colorectal cancer Chemotherapy Drug delivery systems Solubility Targeted Local administration

Genetically programmable cell membrane-camouflaged nanoparticles for targeted combination therapy of colorectal cancer

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2999-3014页

作者： Yun Yang Qingya Liu Meng Wang Lang Li Yan Yu Meng Pan Danrong Hu Bingyang Chu Ying Qu Zhiyong Qian department of biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Cell membrane-camouflaged nanoparticles possess inherent advantages derived from their membrane structure and surface antigens,including prolonged circulation in the bloodstream,specific cell recognition and targeting capabilities,and potential for ***,we introduce a cell membrane biomimetic nanodrug platform termed MPB-3BP@CM *** microporous Prussian blue nanoparticles(MPB NPs)serving as both a photothermal sensitizer and carrier for 3-bromopyruvate(3BP),these nanoparticles are cloaked in a genetically programmable cell membrane displaying variants of signal regulatory proteinα(SIRPα)with enhanced affinity to *** a result,MPB-3BP@CM NPs inherit the characteristics of the original cell membrane,exhibiting an extended circulation time in the bloodstream and effectively targeting CD47 on the cytomembrane of colorectal cancer(CRC)***,blocking CD47 with MPB-3BP@CM NPs enhances the phagocytosis of CRC cells by ***,3BP,an inhibitor of hexokinase II(HK2),suppresses glycolysis,leading to a reduction in adenosine triphosphate(ATP)levels and lactate ***,it promotes the polarization of tumor-associated macrophages(TAMs)towards an anti-tumor M1 ***,integration with MPB NPs-mediated photothermal therapy(PTT)enhances the therapeutic efficacy against *** advantages make MPB-3BP@CM NPs an attractive platform for the future development of innovative therapeutic approaches for ***,it introduces a universal approach for engineering disease-tailored cell membranes for tumor therapy.

关键词： CD47 colorectal cancer

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

Nanotechnology’s frontier in combatting infectious and inflammatory diseases:prevention and treatment

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Signal Transduction and Targeted Therapy 2024年第3期9卷 998-1047页

作者： Yujing Huang Xiaohan Guo Yi Wu Xingyu Chen Lixiang Feng Na Xie Guobo Shen department of biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China Hospitaland West China School of Basic Medical Sciences and Forensic MedicineSichuan Universityand Collaborative Innovation Center for BiotherapyChengdu 610041China

inflammation-associated diseases encompass a range of infectious diseases and non-infectious inflammatory diseases,which continuously pose one of the most serious threats to human health,attributed to factors such as the emergence of new pathogens,increasing drug resistance,changes in living environments and lifestyles,and the aging *** rapid advancements in mechanistic research and drug development for these diseases,current treatments often have limited efficacy and notable side effects,necessitating the development of more effective and targeted anti-inflammatory *** recent years,the rapid development of nanotechnology has provided crucial technological support for the prevention,treatment,and detection of inflammation-associated *** types of nanoparticles(NPs)play significant roles,serving as vaccine vehicles to enhance immunogenicity and as drug carriers to improve targeting and *** can also directly combat pathogens and *** addition,nanotechnology has facilitated the development of biosensors for pathogen detection and imaging techniques for inflammatory *** review categorizes and characterizes different types of NPs,summarizes their applications in the prevention,treatment,and detection of infectious and inflammatory *** also discusses the challenges associated with clinical translation in this field and explores the latest developments and *** conclusion,nanotechnology opens up new possibilities for the comprehensive management of infectious and inflammatory diseases.

关键词： prevention inflammatory treatment

Expanding the horizons of targeted protein degradation:A non-small molecule perspective

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2402-2427页

作者： Xiaowei Huang Fengbo Wu Jing Ye Lian Wang Xiaoyun Wang Xiang Li Gu He department of Pharmacy and department of Dermatology&Venerology West China HospitalSichuan UniversityChengdu 610041China department of Urology West China HospitalSichuan UniversityChengdu 610041China Laboratory of Dermatology Clinical Institute of Inflammation and ImmunologyFrontiers Science Center for Disease-Related Molecular Network and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Targeted protein degradation(TPD)represented by proteolysis targeting chimeras(PROTACs)marks a significant stride in drug discovery.A plethora of innovative technologies inspired by PROTAC have not only revolutionized the landscape of TPD but have the potential to unlock functionalities beyond ***-small-molecule-based approaches play an irreplaceable role in this field.A wide variety of agents spanning a broad chemical spectrum,including peptides,nucleic acids,antibodies,and even vaccines,which not only prove instrumental in overcoming the constraints of conventional small molecule entities but also provided rapidly renewing *** we summarize the burgeoning non-small molecule technological platforms inspired by PROTACs,including three major trajectories,to provide insights for the design strategies based on novel paradigms.

关键词： Targeted protein degradation Proteolysis targeting chimera Endocytosis Autophagy Proximity-inducing modality Post-translational modification

A nonenzymatic electrochemical sensor for the detection of hydrogen peroxide in vitro and in vivo fibrosis models

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Chinese Chemical Letters 2024年第3期35卷 394-398页

作者： Hongyao Liu Yan Yu Taixiong Xue Cailing Gan Yuting Xie Doudou Wang Peilin Li Zhiyong Qian Tinghong Ye department of Gastroenterology and Hepatology Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer and Frontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China department of biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Fibrosis occurs due to the excessive deposition of extracellular matrix caused by cell *** various types of tissue injury,the dysregulation of the internal response can eventually lead to the destruction of organ structure and *** is increasing evidence that oxidative stress,which is characterized by excessive production of hydrogen peroxide(H_(2)O_(2)),is an important cause of ***,we synthesized a biosensitive and efficient electrochemical H_(2)O_(2)sensor based on PtNi nanoparticle-doped N-reduced graphene oxide(PtNi-N-rGO)to detect H_(2)O_(2)released from transforming growth factorβ1(TGFβ1)-induced *** addition,the sensor could easily detect changes in H_(2)O_(2)in the lung and bronchoalveolar lavage fluid(BALF)of mice with pulmonary ***,the sensor could also detect H_(2)O_(2)in activated hepatic stellate cells and the liver of carbon tetrachloride(CCl_(4))-induced liver ***,the alterations in H_(2)O_(2)detected by the sensor were consistent with nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)protein expression and the staining results of pathological *** together,these results highlight the use of H_(2)O_(2)sensors for the rapid detection of fibrosis and facilitate the rapid evaluation of antifibrotic drug candidates.

关键词： Fibrosis H_(2)O_(2) Electrochemical sensor NOX4 Nintedanib

Targeted drug approvals in 2023:breakthroughs by the FDA and NMPA

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Signal Transduction and Targeted Therapy 2024年第3期9卷 813-821页

作者： Lang Zheng Wenjing Wang Qiu Sun department of biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China West China Medical Publishers West China HospitalSichuan UniversityChengdu 610041China

According to the official website of China’s National Medicines and Pharmaceutical Administration(NMPA),a total of 87 novel drugs were approved in China in 2023,with targeted drugs accounting for 67.8%of the total,amounting to 59 drugs(Fig.1a;Table 1)[https://***/yaopin/ypjgdt/***].Notably,domestic innovation is flourishing,with five first-in-class drugs,including Glumetinib,a c-Met inhibitor from Haihe Biopharma;Leritrelvir,a 3CL protease inhibitor from Raynovent;Anaprazole,a proton pump inhibitor from Xuanzhu Biopharm;Pegol-Sihematide,an EPO drug from Hansoh Pharma;and Zuberitamab from BioRay Biopharmaceutical Co.,***,the world’s first allosteric inhibitor targeting TYK2,Sotyktu(deucravacitinib),has been approved for the treatment of psoriasis and Selumetinib,a MEK inhibitor co-developed by AstraZeneca and Merck Sharp&Dohme(MSD),became the first approved drug in China for the treatment of neurofibromatosis type I(NF1).Beyond these drugs,the approval of novel drug types such as CAR-T cell products,siRNA,monoclonal antibodies,dual antibodies,and ADCs in China is a significant development in the country’s pharmaceutical industry(Fig.1a).

关键词： drugs Merck approval

Fc receptor-like 5(FCRL5)-directed CAR-T cells exhibit antitumor activity against multiple myeloma

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Signal Transduction and Targeted Therapy 2024年第2期9卷 724-737页

作者： Zhengyu Yu Hexian Li Qizhong Lu Zongliang Zhang Aiping Tong Ting Niu department of Hematology State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China

Multiple myeloma(MM)remains a challenging hematologic malignancy despite advancements in chimeric antigen receptor T-cell(CAR-T)*** targets of CAR-T cells used in MM immunotherapy have limitations,with a subset of patients experiencing antigen loss resulting in ***,novel targets for enhancing CAR-T cell therapy in MM remain *** receptor-like 5(FCRL5)is a protein marker with considerably upregulated expression in MM and has emerged as a promising target for CAR-T cell therapeutic interventions,offering an alternative treatment for *** further explore this option,we designed FCRL5-directed CAR-T cells and assessed their cytotoxicity in vitro using a co-culture system and in vivo using MM cell-derived xenograft models,specifically focusing on MM with gain of chromosome *** the challenges in CAR-T therapies arising from limited T cell persistence,our approach incorporates interleukin-15(IL-15),which enhances the functionality of central memory T(TCM)cells,into the design of FCRL5-directed CAR-T cells,to improve cytotoxicity and reduce T-cell dysfunction,thereby promoting greater CAR-T cell survival and *** in vitro and xenograft models displayed that FCRL5 CAR-T cells incorporating IL-15 exhibited potent antitumor efficacy,effectively inhibiting the proliferation of MM cells and leading to remarkable tumor *** results highlight the capacity of FCRL5-specific CAR-T cells with the integration of IL-15 to improve the therapeutic potency,suggesting a potential novel immunotherapeutic strategy for MM treatment.

关键词： directed thereby offering

Not to be and how not to be:the questions of Tregs controlled by RIPK1

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Cellular & Molecular Immunology 2024年第2期21卷 205-206页

作者： Zhengcai Peng Huiyuan Zhang Hongbo Hu Center for Immunology and Hematology Department of Biotherapy and Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China Chongqing International Institute for Immunology Chongqing401338China

Millions of cells undergo daily cell death,a process essential for maintaining physiological homeostasis and *** forms of cell death,such as apoptosis,necroptosis,ferroptosis and pyroptosis,have been extensively studied for their distinct biological functions[1,2].Generally,programmed cell death,like apoptosis,is considered physiological and results in little to no inflammatory response.

关键词： death homeostasis pathogenesis