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Biomimetic“Gemini nanoimmunoregulators”orchestrated for boosted photoimmunotherapy by spatiotemporally modulating PD-L1 and tumor-associated macrophages

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1345-1361页

作者： Honglin Huang Ningxi Li Xiaodan Wei Qingzhi Li Junhan Guo Geng Yang Hong Yang Lulu Cai Yiyao Liu Chunhui Wu Department of Pharmacy Personalized Drug Therapy Key Laboratory of Sichuan ProvinceSichuan Provincial People’s Hospitaland School of Life Science and TechnologyUniversity of Electronic Science and Technology of ChinaChengdu 610054China tcm regulating metabolic diseases key laboratory of sichuan province Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072China

A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer ***,a new type of spatiotemporal biomimetic“Gemini nanoimmunoregulators”was engineered to activate robust systemic photoimmunotherapy by integrating the triple-punch of amplified immunogenic cell death(ICD),tumor-associated macrophages(TAMs)phenotype reprogramming and programmed cell death ligand 1(PD-L1)***“Gemini nanoimmunoregulators”PM@RM-T7 and PR@RM-M2 were constructed by taking the biocompatible mesoporous polydopamine(mPDA)as nanovectors to deliver metformin(Met)and toll-like receptor 7/8 agonist resiquimod(R848)to cancer cells and TAMs by specific biorecognition via wrapping of red blood cell membrane(RM)inlaid with T7or M2 ***/Met@RM-T7(abbreviated as PM@RM-T7)was constructed to elicit an amplified in situ ICD effect through the targeted PTT and effectively stimulated the anticancer ***,PD-L1 on the remaining cancer cells was degraded by the burst metformin to prevent immune ***,mPDA/R848@RM-M2(abbreviated as PR@RM-M2)specifically recognized TAMs and reset the phenotype from M2 to M1 state,thus disrupting the immunosuppressive microenvironment and further boosting the function of cytotoxic T *** pair of sister nanoimmunoregulators cooperatively orchestrated the comprehensive anticancer activity,which remarkably inhibited the growth of primary and distant 4T1 tumors and prevented malignant *** study highlights the spatiotemporal cooperative modalities using multiple nanomedicines and provides a new paradigm for efficient cancer immunotherapy against metastatic-prone tumors.

关键词： Biomimetic immunoregulator Spatiotemporal delivery Targeted photothermal therapy Amplified immunogenic cell death Immunosuppressive tumor microenvironment PD-L1 degradation TAMs phenotype reversion Metastasis inhibition

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Myosin regulates intracellular force and guides collective cancer cell migration via the FAK-Rho/ROCK feedback loop

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Genes & diseases 2023年第6期10卷 2199-2201页

作者： Xiang Qin Yuchen He Yixi Zhang Shun Li Tingting Li Fengming You Yiyao Liu Department of Pharmacy Personalized Drug Therapy Key Laboratory of Sichuan ProvinceSichuan Provincial People's HospitalSchool of Life Science and TechnologyUniversity of Electronic Science and Technology of ChinaChengduSichuan 611731China tcm regulating metabolic diseases key laboratory of sichuan province Hospital of Chengdu University of Traditional Chinese MedicineChengduSichuan 610072China

Breast cancerhas been one of the biggest killers of women due to its susceptibility and high *** observations show that malignant cancer cells frequently invade the surrounding normal tissue in collective rather than individual cell migration.1,2 For individual cell migration,it has been found that the Rho/ROCK signaling is upregulated and correlates with disease progression.3 Meanwhile,Rho activates myosin-ll and the actomyosin-mediated contraction creates tension within the cells.4,5 However,the roles of the activation of the Rho/RoCK signal pathway in collective cell migration and the precise mechanisms by which myosin-ll fine-tunes the contractility of the cells to allow for the reorganization of the cytoskeleton that drives collective cell migration,remain *** study investigated whether the high cellular contractility could activate the inside-out signal transductions and how did the intracellular force contribute to the collective cell migration.

关键词： cancer collective migration

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Tirapazamine encapsulated hyaluronic acid nanomicelles realized targeted and efficient photo-bioreductive cascading cancer therapy

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Chinese Chemical Letters 2021年第8期32卷 2400-2404页

作者： Chunhui Wu Qiuyue Liu Yikun Wang Zhengxin Xie Honglin Huang Ningxi Li Xiaodan Wei Geng Yang Tingting Li Hong Yang Shun Li Xiang Qin Yiyao Liu Department of Biophysics School of Life Science and TechnologyUniversity of Electronic Science and Technology of ChinaChengdu 610054China tcm regulating metabolic diseases key laboratory of sichuan province Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072China

Currently,architecting a ratio nal and efficient nanoplatform combing with multi-therapeutic modalities is highly obligatory for advanced cancer *** order to remedy the self-limiting hypoxic dilemma of photodynamic therapy(PDT),herein,a facile photosensitizer(i.e.,chlorin e6,Ce6) and bioreductive prodrug(i.e.,tirapazamine,TPZ)-coloaded hyaluronic acid(HA) nanomicelles(denoted as TPZ@HA-Ce6)was developed for the cascading mode of photo-bioreductive cancer *** the typical advantage of Ce6 coupled HA conjugate,TPZ was easily and successfully accommodated into the hydrophobic core of HA-Ce6 nanomicelles,yielding TPZ@*** showed good dispersibility and stability with the hydrodynamic size of ca.170 *** targeted the CD44 overexpressed cancer cells by receptor-mediated endocytosis way and killed them effectively with singlet oxygen and the subsequent TPZ radicals resulting from the oxygen depletion of *** later was further verified by the hypoxia probe in *** murine mammary carcinoma 4 T1 model,TPZ@HA-Ce6 nanomicelles exhibited cascading and synergistic anticancer effect of PDT and TPZ bioreductive therapy compared with each *** work suggests the promising prospect of the hybrid hyaluronic nanomicelles for highly efficient cancer combination treatment.

关键词： Hyaluronic acid Photosensitizer Bioreductive prodrug Hypoxia Cascading cancer therapy

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Efficacy of press needle on immune function and quality of life in female breast cancer patients after radical mastectomy:study protocol for a randomized controlled trial

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Journal of Traditional Chinese Medicine 2023年第2期43卷 374-378页

作者： GAO Ying WANG Yao CHEN Hongchun YAN Ran LIU Tao ZENG Jinhao LI Zhuohong Oncology Department Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072China Galactophore Department Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072China tcm regulating metabolic diseases key laboratory of sichuan province Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072China

Radical mastectomy may lead to suppression of cellular immune function in patients with malignant tumors,and affect the quality of life(QOL)of *** suppression is a common cause of complications and adverse reactions in adjuvant therapy after radical mastectomy of breast ***,there are few proven effective treatments for immune ***,it’s necessary to develop a new treatment *** needle is widely used in clinical ***,there have been relatively few studies that evaluate the effects of press needle on postoperative immune *** aim of the present study is to assess the effects of press needle on immune function and QOL in female breast cancer patients undergoing radical *** study will be a single-center,randomized and single-blinded *** 78 eligible patients will be randomized in a ratio of 1:1 to the press needle group or the sham press needle *** the treatment phase,patients will undergo five times weekly of verum press needle or sham press needle for 2 *** primary outcome measures will be the peripheral blood levels of CD8^(+),CD4^(+),CD3^(+),and CD4^(+)/CD8^(+)T *** secondary outcome measures will be the changes of patients’QOL,evaluated by the Karnofsky Performance Scale score and the EORTC core quality of life questionnaire(EORTC QLQ-C30).Furthermore,5-year survival rate and recurrence rate will be *** and adverse events will be assessed at each *** results of this on-going study will provide clinical evidence for the effects and safety of press needle on immune function and QOL in patients after breast cancer resection compared with sham press needle.

关键词： breast cancer resection immune function press needle study protocol

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Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction

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World Journal of Stem Cells 2024年第4期16卷 444-458页

作者： Cheng-Jin Ai Ling-Juan Chen Li-Xuan Guo Ya-Ping Wang Zi-Yi Zhao Department of laboratory Medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Department of Ophthalmology Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Central laboratory Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Traditional Chinese Medicine regulating metabolic diseases key laboratory of sichuan province Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina

BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against conventional *** acetic acid(GAA),which is extracted from the seeds of cotton plants,exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting *** To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact *** In this study,LSCs were magnetically sorted from AML cell lines and the CD34+CD38-population was *** expression of leucine-rich pentatricopeptide repeat-containing protein(LRPPRC)and forkhead box M1(FOXM1)was evaluated in LSCs,and the effects of GAA on malignancies and mitochondrial RESULTS LRPPRC was found to be upregulated,and GAA inhibited cell proliferation by degrading *** induced LRPPRC degradation and inhibited the activation of interleukin 6(IL-6)/janus kinase(JAK)1/signal transducer and activator of transcription(STAT)3 signaling,enhancing chemosensitivity in LSCs against conventional chemotherapies,including L-Asparaginase,Dexamethasone,and *** was also found to downregulate FOXM1 indirectly by regulating ***,GAA induced reactive oxygen species accumulation,disturbed mitochondrial homeostasis,and caused mitochondrial *** inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC,GAA resulted in the elimination of ***,GAA induced oxidative stress and subsequent cell damage by causing mitochondrial *** Taken together,the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

关键词： Leukemia stem cells Gossypol acetic acid Reactive oxygen species Mitochondrial dysfunction Interleukin 6/janus kinase 1/signal transducer and activator of transcription 3 signaling

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Functions and clinical significance of mechanical tumor microenvironment:cancer cell sensing,mechanobiology and metastasis

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Cancer Communications 2022年第5期42卷 374-400页

作者： Hanying Zhou Meng Wang Yixi Zhang Qingqing Su Zhengxin Xie Xiangyan Chen Ran Yan Ping Li Tingting Li Xiang Qin Hong Yang ChunhuiWu Fengming You Shun Li Yiyao Liu Department of Biophysics School of Life Science and TechnologyUniversity of Electronic Science and Technology of ChinaChengduSichuan 610054P.R.China Traditional Chinese Medicine regulating metabolic diseases key laboratory of sichuan province Hospital of Chengdu University of Traditional Chinese MedicineChengduSichuan 610072P.R.China

Dynamic and heterogeneous interaction between tumor cells and the surrounding microenvironment fuels the occurrence,progression,invasion,and metastasis of solid *** this process,the tumormicroenvironment(TME)fractures cellular and matrix architecture normality through biochemical and mechanical means,abetting tumorigenesis and treatment *** cells sense and respond to the strength,direction,and duration of mechanical cues in the TME by various mechanotransduction ***,far less understood is the comprehensive perspective of the functions and mechanisms of *** to the great therapeutic difficulties brought by the mechanical changes in the TME,emerging studies have focused on targeting the adverse mechanical factors in the TME to attenuate disease rather than conventionally targeting tumor cells themselves,which has been proven to be a potential therapeutic *** this review,we discussed the origins and roles ofmechanical factors in the TME,cell sensing,mechano-biological coupling and signal transduction,in vitro construction of the tumormechanicalmicroenvironment,applications and clinical significance in the TME.

关键词： tumor microenvironment mechanical model mechanosensing mechanotransduction cytoskeleton remodelin

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Remodeling tumor immunosuppressive microenvironment via a novel bioactive nanovaccines potentiates the efficacy of cancer immunotherapy

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Bioactive Materials 2022年第10期7卷 107-119页

作者： Xiaoxue Xie Yi Feng Hanxi Zhang Qingqing Su Ting Song Geng Yang Ningxi Li Xiaodan Wei Tingting Li Xiang Qin Shun Li Chunhui Wu Xiaojuan Zhang Guixue Wang Yiyao Liu Hong Yang Department of Biophysics School of Life Science and TechnologyUniversity of Electronic Science and Technology of ChinaChengdu610054SichuanPR China tcm regulating metabolic diseases key laboratory of sichuan province Hospital of Chengdu University of Traditional Chinese MedicineNo.39 Shi-er-qiao RoadChengdu610072SichuanPR China key laboratory of Biorheological Science and Technology Ministry of EducationState and Local Joint Engineering Laboratory for Vascular ImplantsBioengineering College of Chongqing UniversityChongqing400030PR China

The clinical outcomes of cancer nanovaccine have been largely impeded owing to the low antigen-specific T cell response rate and acquired resistance caused by the immunosuppressive tumor microenvironment(TME).Here,we reported a tumor acidity-responsive nanovaccine to remodel the immunosuppressive TME and expand the recruitment of tumor infiltrating lymphocytes(TILs)using hybrid micelles(HM),which encapsulated colony stimulating factor 1 receptor(CSF1-R)inhibitor BLZ-945 and indoleamine 2,3-dioxygenase(IDO)inhibitor NLG-919 in its core and displayed a model antigen ovalbumin(OVA)on its surface(denoted as BN@HM-OVA).The bioactive nanovaccine is coated with a polyethylene glycol(PEG)shell for extending nanoparticle *** shell can be shed in response to the weakly acidic tumor *** decrease in size and the increase in positive charge may cause the deep tumor penetration of *** demonstrated that the bioactive nanovaccine dramatically enhance antigen presentation by dendritic cells(DCs)and drugs transportation into M1-like tumor-associated macrophages(TAMs)and tumor cells via size reduction and increasing positive charge caused by the weakly acidic *** bioactive nanovaccine could remodel the immunosuppressive TME into an effector T cells favorable environment,leading to tumor growth inhibition in prophylactic and therapeutic E.G7-OVA tumor ***,combining the bioactive nanovaccine with simultaneous anti-PD-1 antibody treatment leads to a long-term tumor inhibition,based on the optimal timing and sequence of PD-1 blockade against T cell *** research provides a new strategy for the development of efficient cancer immunotherapy.

关键词： Bioactive nanovaccine Cancer immunotherapy IDO inhibitor TAMs TME

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Natural bioactive flavonoids as promising agents in alleviating exercise-induced fatigue

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Food Bioscience 2023年第1期51卷 109-120页

作者： Yuzhou Liu Xiaofei Shen Mengxiang Sha Zige Feng Yue Liu Chengdu Sport University ChengduChina State key laboratory of Southwestern Chinese Medicine Resources School of Ethnic MedicineChengdu University of Traditional Chinese MedicineChengduChina tcm regulating metabolic diseases key laboratory of sichuan province Hospital of Chengdu University of Traditional Chinese MedicineChengdu University of Traditional Chinese MedicineChengduChina School of Pharmacy Southwest Minzu UniversityChengdu610225China

Exercise-induced fatigue is a common phenomenon caused by prolonged strenuous exercise and physical labor as a feeling of exhaustion and reduction of muscle performance,which seriously affects people’s health,work efficiency and quality of ***,numerous studies have shown that natural flavonoids can be an excellent source for preventing and treating exercise-induced fatigue due to their extraordinary antioxidant and antiinflammatory ***,the review of flavonoids in alleviating exercise-induced fatigue is still ***,this review systematically summarizes recent studies on natural bioactive flavonoids that can alleviate exercise-induced fatigue and improve physical performance,including their plant sources,structure types and features,pharmacological effects and underlying mechanisms against exercise-induced ***,the clinical trials have also been ***,isoflavones,anthocyanins,and their corresponding glycosides are the major bioactive flavonoids in alleviating exercise-induced *** current data and the further molecular docking evidently support the potential anti-fatigue effects of these flavonoids mainly involving the inhibition of oxidative stress and inflammatory response,as well as the regulation of energy *** of the Keap1/Nrf2/ARE and AMPK/PGC1-αpathways are responsible for the improvement of flavonoids against exercise-induced ***,this review is expected to contribute to the further research and development of anti-fatigue flavonoids in the functional food and nutraceutical industry.

关键词： Natural bioactive flavonoids Exercise-induced fatigue Antioxidant Anti-inflammatory Energy metabolism

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ROCK inhibitor:Focus on recent updates

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Chinese Chemical Letters 2023年第12期34卷 111-125页

作者： Yaodong You Kun Zhu Jie Wang Qi Liang Wen Li Lin Wang Baojun Guo Jing Zhou Xuanlin Feng Jianyou Shi Hospital of Chengdu University of Traditional Chinese Medicine Chengdu 610072China tcm regulating metabolic diseases key laboratory of sichuan province Chengdu 610072China Guizhou University of Traditional Chinese Medicine Guiyang 550002China College of Medicine Southwest Jjiaotong UniveChengdu 610031China College of Food and Bioengineering Xihua UniversityChengdu 610039China Department of Emergency Intensive Care Unit Sichuan Academy of Medical Sciences&Sichuan Province People's HospitalChengdu 610072China Department of Pharmacy Personalized Drug Therapy Key Laboratory of Sichuan ProvinceSichuan Academy of Medical Sciences&Sichuan Provincial People's HospitalSchool of MedicineUniversity of Electronic Science and TechnologyChengdu 610072China

Rho-associated coiled-coil-containing protein kinase(RoCK)belongs to the serine-threonine family,and RoCK is involved in a variety of biological processes including cell migration,adhesion,proliferation and differentiation through phosphorylation of different downstream *** aberrant activation of ROCK is associated with the pathological conditions in different systems including various diseases,including cancer,neurological diseases,inflammation,cardiovascular diseases and ***,the ROCK inhibitors have potential applicability for treating the aforementioned *** small molecule ROCK inhibitors have been approved for clinical use:fasudil,ripasudil,netarsudil and *** recent years,more small molecule ROCK inhibitors have been *** paper reviews the ROCK inhibitors reported in past seven *** mainly focused on the summarization of the structure-activity relationships,inhibitory efficacy,pharmacological mechanisms and the relevant clinical studies of the reported ROCK *** the small molecular inhibitors,the peptides and biological extracts which exhibit ROCK inhibitory effects are also *** also provide suggestions for the future development of the potent ROCK inhibitors.

关键词： ROCK-I ROCK-I ROCK inhibitor ROCK signaling pathway Structure-activity relationship Pharmacological activity

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Corrigendum to “Remodeling tumor immunosuppressive microenvironment via a novel bioactive nanovaccines potentiates the efficacy of cancer immunotherapy” [Bioactive Mater. 16 107-119]

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Bioactive Materials 2023年第3期21卷 239-240页

The authors regret that the published version of the above article contained two errors which were not identified during the proofing ***,Figure 2A and 6C have been *** authors apologize for these errors and state tha... 详细信息

关键词： Cor vaccines immunotherapy

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