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Monkeypox:epidemiology,pathogenesis,treatment and prevention

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Signal Transduction and Targeted Therapy 2022年第12期7卷 4261-4282页

作者： Yong Huang Li Mu Wei Wang Department of biotherapy State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengduChina

Monkeypox is a zoonotic disease that was once endemic in west and central Africa caused by monkeypox ***,cases recently have been confirmed in many nonendemic countries outside of *** declared the ongoing monkeypox outbreak to be a public health emergency of international concern on July 23,2022,in the context of the COVID-19 *** rapidly increasing number of confirmed cases could pose a threat to the international ***,we review the epidemiology of monkeypox,monkeypox virus reservoirs,novel transmission patterns,mutations and mechanisms of viral infection,clinical characteristics,laboratory diagnosis and treatment *** addition,strategies for the prevention,such as vaccination of smallpox vaccine,is also *** epidemiological data indicate that high frequency of human-to-human transmission could lead to further outbreaks,especially among men who have sex with *** development of antiviral drugs and vaccines against monkeypox virus is urgently needed,despite some therapeutic effects of currently used drugs in the *** provide useful information to improve the understanding of monkeypox virus and give guidance for the government and relative agency to prevent and control the further spread of monkeypox virus.

关键词： epidemiology prevention drugs treatment

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

Intravesical chemotherapy synergize with an immune adjuvant by a thermo-sensitive hydrogel system for bladder cancer

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Bioactive Materials 2024年第1期31卷 315-332页

作者： J.Liu T.Y.Yang L.Q.Dai K.Shi Y.Hao B.Y.Chu D.R.Hu Z.W.Bei L.P.Yuan M.Pan Z.Y.Qian Department of biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China

Surgical resection remains the prefer option for bladder cancer ***,the effectiveness of surgery is usually limited for the high recurrence rate and poor ***,intravesical chemotherapy synergize with immunotherapy in situ is an attractive way to improve therapeutic ***,a combined strategy based on thermo-sensitive PLEL hydrogel drug delivery system was *** loaded PLEL hydrogel was intravesical instilled to kill tumor cells directly,then PLEL hydrogel incorporated with CpG was injected into both groins subcutaneously to promote immune responses synergize with *** results demonstrated that drug loaded PLEL hydrogel had a sol-gel phase transition behavior in response to physiological temperature and presented sustained drug release,and the PLEL-assisted combination therapy could have better tumor suppression effect and stronger immunostimulating effect in ***,this combined treatment with PLEL hydrogel system has great potential and suggests a clinically-relevant and valuable option for bladder cancer.

关键词： Thermo-responsive hydrogel Localized drug delivery Intravesical chemotherapy Immunotherapy Bladder 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

Incorporation of a Toll-like receptor 2/6 agonist potentiates mRNA vaccines against cancer and infectious diseases

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3806-3817页

作者： Yangzhuo Gu Jingyun Yang Cai He Tingmei Zhao Ran Lu Jian Liu Xianming Mo Fuqiang Wen Huashan Shi Department of biotherapy State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan Universityand Collaborative Innovation Center for BiotherapyChengduSichuan 610041China Division of Pulmonary Diseases State Key Laboratory of Biotherapy and Department of Respiratory and Critical Care MedicineWest China HospitalSichuan UniversityChengduSichuan 610041China laboratory of Stem Cell Biology and Department of Pediatric Surgery State Key Laboratory of BiotherapyWest China HospitalSichuan Universityand Collaborative Innovation Center for BiotherapyChengduSichuan 610041China

mRNA vaccines have emerged rapidly in recent years as a prophylactic and therapeutic agent against various diseases including cancer and infectious *** of mRNA vaccines have been underway,among which boosting of efficacy is of great ***2Cys,a simple synthetic metabolizable lipoamino acid that signals through Toll-like receptor(TLR)2/6 pathway,eliciting both humoral and cellular adaptive immune responses,is an interesting candidate *** investigate the enhancement of the efficacies of mRNA vaccines by Pam2Cys,the adjuvant was incorporated into mRNA-lipid nanoparticles(LNPs)to achieve co-delivery with *** with the resulting mRNA-LNPs(Pam2Cys)shaped up the immune milieu in the draining lymph nodes(dLNs)through the induction of IL-12 and IL-17,among other *** presentation was carried out mainly by migratory and dLNresident conventional type 2 DCs(cDC2s)and significantly more potent antitumor responses were triggered in both prophylactic and therapeutic tumor models in a CD4^(+) and CD8^(+) T cell-dependent *** memory antitumor immunity was also ***,the vaccine also stimulated much more robust humoral and cellular immunity in a surrogate COVID-19 prophylactic *** but not the least,the new vaccines exhibited good preliminary safety profiles in murine *** facts warrant future development of Pam2Cys-incorporated mRNA vaccines or relevant mRNA therapeutics for clinical application.

关键词： vaccines immunity diseases

A new sensitization strategy for achieving organic RTP in aqueous solution:tunable RTP and UC emission in supramolecular TTA-UC systems

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Science China Chemistry 2023年第12期66卷 3546-3554页

作者： Lingling Wei Fanrui Gao Cheng He Qiuhui He Pengyue Jin Yanqin Rong Ting Zhao Cheng Yang Wanhua Wu key laboratory of Green Chemistry&Technology of Ministry of Education College of ChemistryState Key Laboratory of BiotherapySichuan UniversityChengdu 610064China

Achieving room temperature phosphorescence(RTP)of heavy-atom-free organic molecules with near-infrared(NIR)emission in solutions is fascinating for medical and biological applications but is highly ***,we report a new sensitization strategy to achieve RTP of heavy-atom-free fluorophores which served as energy acceptors in triplet-triplet annihilation upconversion(TTA-UC)by carefully designing the accommodated microenvironments through non-covalent interactions with a PAMAM dendrimer *** RTP of a serial of diphenyl anthracene(DPA)derivatives peaked at 766 nm were observed for the first time in an aqueous solution with a maximal quantum yield of 1.4%.A ternary supramolecular assembling between the UC components and the dendrimers was formed via electrostatic interaction between the–COOH and peripheral amino *** one hand,it assured the efficient population of the triplet states of the fluorophore via triplet-triplet energy transfer(TTET)process;on the other hand,it restricted the motions of the fluorophores,and thus inhibited the nonradiative inactivation of the populated triplet *** two aspects jointly contributed to the sensitized RTP of DPA ***,the microenvironment in which the annihilators resided could be regulated by adjusting the ratio of carboxyl to amino groups(–COOH/–NH_(2)),when–COOH/–NH_(2)1,the UC components could be partly driven to the hydrophobic cavities of the dendrimers,resulting an unprecedentedly simultaneous emission of upconverted fluorescence and down-converted phosphorescence of the annihilators.

关键词： room temperature phosphorescence sensitization supramolecular assembling dendrimer

Neurons generated from carcinoma stem cells support cancerprogression

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Signal Transduction and Targeted Therapy 2017年第1期2卷 320-329页

作者： Ran Lu Chuanwen Fan Wenqi Shangguan Yuan Liu Yu Li Yanna Shang Dongqin Yin Shengliang Zhang Qiaorong Huang Xue Li Wentong Meng Hong Xu Zongguang Zhou Jiankun Hu Weimin Li Lunxu Liu Xianming Mo laboratory of Stem Cell Biology State Key Laboratory of Biotherapy/Collaborative Innovation Center of BiotherapyWest China HospitalSichuan UniversityChengduChina Institute of Digestive Surgery State Key Laboratory of Biotherapy/Collaborative Innovation Center of BiotherapyWest China HospitalSichuan UniversityChengduChina Department of Gastrointestinal Surgery State Key Laboratory of Biotherapy/Collaborative Innovation Center of BiotherapyWest China HospitalSichuan UniversityChengduChina laboratory of Gastric Cancer State Key Laboratory of Biotherapy/Collaborative Innovation Center of BiotherapyWest China HospitalSichuan UniversityChengduChina Department of Respiratory and Critical Care Medicine State Key Laboratory of Biotherapy/Collaborative Innovation Center of BiotherapyWest China HospitalSichuan UniversityChengduChina Department of Thoracic Surgery State Key Laboratory of Biotherapy/Collaborative Innovation Center of BiotherapyWest China hospitalSichuan UniversityChengduChina.

Recent evidences show that nervous system acts as a crucial part of cancer *** of nerve fibers into cancer microenvironment has an important active role in cancer *** stimulations of both cancer growth and metastasis by members of nervous system such as neurons and glial cells have been ***,how the nervous system is built in cancer is largely *** we show that a fraction of cancer stem cells(CSCs)derived from patients with gastric carcinoma and colorectal carcinoma are capable of producing neurons that are involved in tumor neurogenesis and tumor *** stem cell monoclone derived from a single cancer stem cell was able to generate neurons including sympathetic and parasympathetic neurons to take part in the nervous system in cancer *** down the neural cell generating capability of the human CSCs inhibited the growth of xenograft tumors in mouse *** data demonstrate that human CSCs are able to produce one of most important components in the cancer microenvironment that are required for cancer development and progression.

关键词： cancer inhibited stimulation

WT-PE:Prime editing with nuclease wild-type Cas9 enables versatile large-scale genome editing

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Signal Transduction and Targeted Therapy 2022年第5期7卷 1756-1763页

作者： Rui Tao Yanhong Wang Yun Hu Yaoge Jiao Lifang Zhou Lurong Jiang Li Li Xingyu He Min Li Yamei Yu Qiang Chen Shaohua Yao From laboratory of biotherapy National Key Laboratory of BiotherapyCancer CenterWest China HospitalSichuan universityRenmin Nanlu 17Chengdu 610041 SichuanChina

Large scale genomic aberrations including duplication,deletion,translocation,and other structural changes are the cause of a subtype of hereditary genetic disorders and contribute to onset or progress of *** current prime editor,PE2,consisting of Cas9-nickase and reverse transcriptase enables efficient editing of genomic deletion and insertion,however,at small ***,we designed a novel prime editor by fusing reverse transcriptase(RT)to nuclease wild-type Cas9(WT-PE)to edit large genomic fragment.

关键词： Cas9 nuclease editor