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Zwitterionic hyaluronic acid derivatives for co-delivery of both chemotherapeutic and nucleic acid drugs in breast cancer treatment

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Nano Research 2025年第1期18卷 607-617页

作者： Ruo-Lin Jiang Hui-Na Liu Yu-Fan Yang Zhi-Cheng Zhang Qi Dai Xiao-Yan Bao Lin-Jie Wu Ya-Xin Qin Xin Tan Xiao-Yan Sun Xu-Fang Ying Zhi-Qing Ben Min Han Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Department of Radiation Oncology Key Laboratory of Cancer Prevention and InterventionThe Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310058China Hangzhou Institute of Innovative Medicine Zhejiang UniversityHangzhou 310058China Jinhua Institute of Zhejiang University Jinhua 321299China National Key laboratory of Advanced Drug Delivery and Release systems Zhejiang UniversityHangzhou 310058China Polytechnic institute Zhejiang UniversityHangzhou 310015China

Traditionally,hyaluronic acid has been widely used for drug delivery,but the current application bottleneck is that hyaluronic acid is hydrophilic and electronegative,which makes it difficult to carry hydrophobic drugs and small interfering RNA(siRNA)with the same *** on previous studies,we designed and synthesized hyaluronic acid nanocarriers HA-spermine/N,N,N-trimethylcystamine/DOX-TPP(HSTD)for loading siRNA to overcome the problem of siRNA release caused by strong electrostatic ***,N,N,Ntrimethylcystamine in the carrier can be degraded by intracellular glutathione to completely and rapidly release siRNA,thus promoting ***,when codelivered with the chemotherapy drug doxorubicin(DOX),this novel nanocarrier showed promising synergy in inhibiting tumor growth.

关键词： zwitterionic hyaluronic acid N N N-trimethylcystamine small interfering RNA(siRNA) doxorubicin

Branched module-modified SN38 prodrug nanoassemblies for improved colorectal cancer therapy:Effectively balance efficacy and safety

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Nano Research 2025年第1期18卷 572-585页

作者： Qing Wang Shiyi Zuo Shufang Zheng Cuiyun Liu Yaqiao Li Jiayu Guo Danping Wang Shuo Wang Wenjing Wang Bowen Zhang Minglong Huang Xianbao Shi Jin Sun Zhonggui He Bingjun Sun Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China Joint International Research laboratory of Intelligent Drug Delivery systems Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China School of Chemical Engineering The University of AdelaideAdelaideSA 5005Australia Department of Pharmacy The First Affiliated Hospital of Jinzhou Medical UniversityJinzhou 121001China

The clinical utility of irinotecan is restricted by individual variability in carboxylesterase *** administration of its active metabolite,7-ethyl-10-hydroxycamptothecin(SN38),presents an appealing alternative due to its potent anti-tumor ***,the undesirable properties of SN38,such as poor water solubility and nontarget toxicity,present significant hurdles to its clinical *** nanoassemblies based on modular design strategy show promise in overcoming these challenges by enhancing drug delivery and selective *** modular design,the modification module plays a crucial role in improving the self-assembly capability of *** current studies mainly focus on using straight aliphatic chains for prodrug design,branched aliphatic chains emerge as superior alternatives warranting further *** this study,we selected 2-heptylundecanol(BAlc18)as modification module to construct an SN38 *** exquisite design,SN38-SS-BAlc18 NPs integrated prominent properties in selfassembly capability,specific activation and biocompatibility,resolving the challenges of irinotecan and SN38,ultimately demonstrating excellent anti-tumor *** exploration enriched the design theory of prodrug nanoassemblies that can effectively balance safety and colorectal anti-tumor efficacy.

关键词： irinotecan SN38 prodrug nanoassemblies disulfide bonds branched aliphatic chains

A citrullinated antigenic vaccine in treatment of autoimmune arthritis

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Science Bulletin 2024年第18期69卷 2920-2929页

作者： Xu Jin Tianya Dong Qian Wang Yang Xie Xiangyu Fang Chaonan Wei Shuyan Liu Xi Zheng Ping Wang Danxue Zhu Lulu Cao Suwei Dong Kechi Fang Chao Zhong Jing Wang Fanlei Hu Zhanguo Li Department of Rheumatology and immunology Peking University People’s Hospital&Beijing Key Laboratory for Rheumatism Mechanism and Immune DiagnosisBeijing 100044China Peking-Tsinghua Center for Life Sciences Peking UniversityBeijing 100871China CAS Key laboratory of Mental Health Institute of PsychologyChinese Academy of SciencesBeijing 100101China Department of Psychology University of Chinese Academy of SciencesBeijing 100049China Department of Chemical Biology School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Institute of systems Biomedicine Department of ImmunologyNHC Key Laboratory of Medical Immunology(Peking University)Beijing Key Laboratory of Tumor Systems BiologyPeking University Health Science CenterBeijing 100191China State Key laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Integration of Chinese and Western Medicine School of Basic Medical SciencesPeking UniversityBeijing 100191China

Rheumatoid arthritis(RA)is an inflammatory autoimmune disease triggered by antigenic peptides with environmental and genetic risk *** has been shown that antigen-specific targeting could be a promising therapeutical strategy for RA by restoring immune tolerance to self-antigens without compromising normal *** of antigens enhances antigenic properties and induces autoimmune ***,we showed that citrullinated antigenic(citAg)vaccine ameliorated collageninduced arthritis with decreased T-helper 1(Th1)and Th17 cells,downregulated proinflammatory cytokines including interlukin-6 and tumor necrosis factor-a,and inhibited antigen recall responses.B cell receptor sequencing further revealed that citAg vaccine could dampen the dysregulated V(D)J recombination,restoring the immune *** together,the results demonstrated that citAg vaccine might have a therapeutic effect on RA.

关键词： CitAg Citrullination Collagen typeⅡ Therapeutic vaccine Immune tolerance Rheumatoid arthritis

A novel role for mitochondrial fission in macrophages: trained innate immunity induced by beta-glucan

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Cellular & Molecular immunology 2023年第8期20卷 864-866页

作者： Anna Brichkina Hans-Uwe Simon Institute of systems immunology Center for Tumor Biology and ImmunologyPhilipps University of Marburg35043MarburgGermany Member of the German Center for Lung Research(DZL) Philipps University of Marburg35043MarburgGermany laboratory of Molecular immunology Institute of Fundamental Medicine and BiologyKazan Federal University420012KazanRussia Institute of Pharmacology University of Bern3010BernSwitzerland Institute of Biochemistry Brandenburg Medical School16816NeuruppinGermany

In a recent paper published in Nature immunology,Ding et *** new insights into the mechanism of how trained innate immunity could eradicate *** authors demonstrated that yeast-derived whole beta-glucan particles(WGP)increased the responsiveness of lung interstitial macrophages to tumor-derived factors associated with the subsequent inhibition of tumor metastasis through enhanced cytotoxicity to cancer *** authors identified the metabolic sphingolipid–mitochondrial fission axis in WGP-trained macrophages as the key pathway responsible for this phenomenon and categorized it as a mechanism of trained innate immunity[1].

关键词： subsequent insight immunity

The role of caveolin-1 in the biofate and efficacy of anti-tumor drugs and their nano-drug delivery systems

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Acta Pharmaceutica Sinica B 2021年第4期11卷 961-977页

作者： Canyu Yang Bing He Wenbing Dai Hua Zhang Ying Zheng Xueqing Wang Qiang Zhang Department of Pharmacy Administration and Clinical Pharmacy School of Pharmaceutical SciencePeking UniversityBeijing 100191China Beijing Key laboratory of Molecular Pharmaceutics New Drug Delivery SystemsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China State Key laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China State Key laboratory of Natural and Biomimetic Drugs Peking UniversityBeijing 100191China

As one of the most important components of caveolae,caveolin-1 is involved in caveolaemediated endocytosis and transcytosis pathways,and also plays a role in regulating the cell membrane cholesterol homeostasis and mediating signal *** recent years,the relationship between the expression level of caveolin-1 in the tumor microenvironment and the prognostic effect of tumor treatment and drug treatment resistance has also been widely *** addition,the interplay between caveolin-1 and nano-drugs is ***-1 could determine the intracellular biofate of specifc nano-drugs,preventing from lysosomal degradation,and facilitate them penetrate into deeper site of tumors by transcytosis;while some nanocarriers could also affect caveolin-1 levels in tumor cells,thereby changing certain biophysical function of *** article reviews the role of caveolin-1 in tumor prognosis,chemotherapeutic drug resistance,antibody drug sensitivity,and nano-drug delivery,providing a reference for the further application of caveolin-1 in nano-drug delivery systems.

关键词： Caveolin-1 Cancer Drug resistance Transcytosis Nano-drug delivery systems Biofate

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Sympathetic nerve signals: orchestrators of mammary development and stem cell vitality

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Journal of Molecular Cell Biology 2024年第5期16卷 29-45页

作者： Zi Ye Yu Xu Mengna Zhang Cheguo Cai Department of Pulmonary Oncology Hubei Province Cancer Clinical Study CenterHubei Key Laboratory of Tumor Biological BehaviorsZhongnan Hospital of Wuhan UniversityFrontier Science Center for Immunology and MetabolismMedical Research InstituteWuhan UniversityWuhan 430071China Key laboratory of systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China

The mammary gland is a dynamic organ that undergoes significant changes at multiple stages of postnatal *** the roles of systemic hormones and microenvironmental cues in mammary homeostasis have been extensively studied,the influence of neural signals,particularly those from the sympathetic nervous system,remains poorly ***,using a mouse mammary gland model,we delved into the regulatory role of sympathetic nervous signaling in the context of mammary stem cells and mammary *** findings revealed that depletion of sympathetic nerve signals results in defective mammary development during puberty,adulthood,and pregnancy,accompanied by a reduction in mammary stem cell *** in vitro three-dimensional culture and in vivo transplantation analyses,we demonstrated that the absence of sympathetic nerve signals hinders mammary stem cell self-renewal and regeneration,while activation of sympathetic nervous signaling promotes these ***,sympathetic nerve signals orchestrate mammary stem cell activity and mammary development through the extracellular signal-regulated kinase signaling ***,our study unveils the crucial roles of sympathetic nerve signals in sustaining mammary development and regulating mammary stem cell activity,offering a novel perspective on the involvement of the nervous system in modulating adult stem cell function and organ development.

关键词： mammary development mammary stem cells sympathetic nerve mammary microenvironment

Methyltransferase-like 3(METTL3)inhibition potentiates anti-tumor immunity:a novel strategy for improving anti-PD1 therapy

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Signal Transduction and Targeted Therapy 2024年第1期9卷 10-11页

作者： Anna Brichkina Roman Suezov Magdalena Huber Institute of systems immunology Member of the German Center for Lung Research(DZL)Philipps University of Marburg35043 MarburgGermany

In a recent article published in Cancer Discovery,Guirguis et *** that enzymatic inhibitors of the m6 A methyltransferase METTL3 induced a formation of immunostimulatory doublestranded mRNAs(dsRNAs)in cancer cells,which triggered a profound tumor-cell-intrinsic interferon response leading to an enhanced antigen presentation and thereby increased killing of tumor cells by cytotoxic CD8+*** inhibition of METTL3 synergized with anti-PD1 immunotherapy,highlighting its potential for improving cancer treatment.

关键词： PD1 immunity

VHH212 nanobody targeting the hypoxia-inducible factor 1α suppresses angiogenesis and potentiates gemcitabine therapy in pancreatic cancer in vivo

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Cancer Biology & Medicine 2021年第3期18卷 772-787页

作者： Guangbo Kang Min Hu He Ren Jiewen Wang Xin Cheng Ruowei Li Bo Yuan Yasmine Balan Zixuan Bai He Huang Department of Biochemical Engineering School of Chemical Engineering&TechnologyTianjin UniversityTianjin 300350China Key laboratory of systems Bioengineering(Ministry of Education) Tianjin UniversityTianjin 300072China Department of Gastroenterology Center of Tumor Immunology and CytotherapyMedical Research Center of The Affiliated Hospital of Qingdao UniversityQingdao 266003China Department of Chemical and Biological Engineering University of OttawaOttawa KIN 6N5Canada

Objective:We aimed to develop a novel anti-HIF-1αintrabody to decrease gemcitabine resistance in pancreatic cancer ***:Surface plasmon resonance and glutathione S-transferase pull-down assays were conducted to identify the binding affinity and specificity of anti-HIF-1αVHH212[a single-domain antibody(nanobody)].Molecular dynamics simulation was used to determine the protein-protein interactions between hypoxia-inducible factor-1α(HIF-1α)and *** real-time polymerase chain reaction(PCR)and Western blot analyses were performed to identify the expressions of HIF-1αand VEGF-A in pancreatic ductal adenocarcinoma cell *** efficiency of the VHH212 nanobody in inhibiting the HIF-1 signaling pathway was measured using a dual-luciferase reporter ***,a PANC-1 xenograft model was developed to evaluate the anti-tumor efficiency of combined *** analysis was conducted to detect the expressions of HIF-1αand VEGF-A in tumor ***:VHH212 was stably expressed in tumor cells with low cytotoxicity,high affinity,specific subcellular localization,and neutralization of HIF-1αin the cytoplasm or *** binding affinity between VHH212 and the HIF-1αPAS-B domain was 42.7 n *** competitive inhibition of the HIF-1αheterodimer with an aryl hydrocarbon receptor nuclear translocator was used to inhibit the HIF-1/VEGF pathway in *** with single agent gemcitabine,co-treatment with gemcitabine and a VHH212-encoding adenovirus significantly suppressed tumor growth in the xenograft model with 80.44%tumor ***:We developed an anti-HIF-1αnanobody and showed the function of VHH212 in a preclinical murine model of PANC-1 pancreatic *** combination of VHH212 and gemcitabine significantly inhibited tumor *** results suggested that combined use of anti-HIF-1αnanobodies with first-line treatment may in the future be an effective treatment for pancreatic cancer.

关键词： Pancreatic cancer nanobody therapeutic intracellular antibody HIF-1αinhibitor gemcitabine chemosensitizer

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Mitochondria in cancer:at the crossroads of life and death

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Chinese Journal of Cancer 2011年第8期30卷 526-539页

作者： Vanessa C.Fogg Nathan J.Lanning Jeffrey P.MacKeigan laboratory of systems Biology Van Andel Research InstituteGrand Rapids

Mitochondrial processes play an important role in tumor initiation and *** this review,we focus on three critical processes by which mitochondrial function may contribute to cancer:through alterations in glucose metabolism,the production of reactive oxygen species (ROS) and compromise of intrinsic apoptotic *** in cancer glucose metabolism include the Warburg effect,leading to a shift in metabolism away from aerobic respiration toward glycolysis,even when sufficient oxygen is present to support *** alterations in cellular metabolism may favor tumor cell growth by increasing the availability of biosynthetic intermediates needed for cellular growth and *** in specific metabolic enzymes,namely succinate dehydrogenase,fumarate hydratase and the isocitrate dehydrogenases,have been linked to human *** ROS may contribute to cancer via DNA damage and the activation of aberrant signaling ***-dependent stabilization of the transcription factor hypoxia-inducible factor (HIF) may be a particularly important event for *** function of intrinsic apoptosis removes an important cellular safeguard against cancer and has been implicated in tumorigenesis,tumor metastasis,and *** of the major mitochondrial processes is *** this review,we outline the connections between them and address ways these mitochondrial pathways may be targeted for cancer therapy.

关键词：抗癌症线粒体十字路口异柠檬酸脱氢酶细胞凋亡肿瘤细胞琥珀酸脱氢酶缺氧诱导因子

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