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Dual inhibition of glucose uptake and energy supply synergistically restrains the growth and metastasis of breast cancer

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Chinese Chemical Letters 2023年第4期34卷 127-132页

作者： Yuan Xu Liling Huang Yuyang Bi Qi Song Mengmeng Zhang Lingfeng Zhang Tianjiao Zhou Lei Xing Hulin Jiang State key laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China jiangsu key laboratory of druggability of biopharmaceuticals China Pharmaceutical UniversityNanjing 210009China

Metastatic breast cancer(MBC) is one of the most common and knotty diseases in female population which could place them in a life-threatening condition. For malignant proliferation and migration, cancer cells require a large amount of glucose and energy to meet the demand of rapid metabolism. Hence,efficiently diminishing the utilization of energy substances by cancer cells is emerging as validated therapeutic strategies for cancer therapy. Herein, a nanoplatform with dual-inhibition of glucose uptake and oxidative phosphorylation(OXPHOS) was designed, which consisted of albendazole(ABZ) and atovaquone(ATO) by simple carrier-free self-assembling. The introduction of ABZ could evidently decrease glucose uptake to reduce the main “energy fuel” of cancer cells. Meanwhile, as a blocker of OXPHOS, ATO would reduce adenosine triphosphate(ATP) production and ameliorate hypoxia microenvironment by suppressing mitochondrial respiratory chain. Under such dual inhibition of energy metabolism, AA NPs exerted synergistic energy exhaustion effect and outstanding hypoxia improvement function, efficiently inhibiting tumor growth and metastasis. This research not only illustrates the feasibility of energy metabolism therapy by co-inhibiting glucose uptake and OXPHOS, but also provides an ingenious tactic to diminish metastasis during MBC treatment.

关键词： Metastatic breast cancer Self-assembled nanosystem Energy exhaustion Hypoxia alleviation Synergistic therapy

Metal ions-bridged J-aggregation mediated nanoassembly composition for breast cancer phototherapy

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Asian Journal of Pharmaceutical Sciences 2022年第2期17卷 230-240页

作者： Chen Chen Shan Yang Yufei Liu Yue Qiu Jing Yao State key laboratory of Natural Medicines and jiangsu key laboratory of druggability of biopharmaceuticals Department of PharmaceuticsChina Pharmaceutical UniversityNanjing 211198China

Recently, the highly ordered J-aggregates of organic dyes with intriguing optical properties have received considerable attention in biomedical applications. Herein, binary metal ions Mn(Ⅱ)/Fe(Ⅲ) are used to induce the formation of indocyanine green(ICG) ***, the sheet-like J-aggregates are able to act as "carriers" for loading hydrophobic chemotherapeutic gambogic acid(GA), realizing the effect of "killing two birds with one stone" for both treatment and delivery. The as-designed nanoassembly is formed spontaneously in aqueous environment via π-π stacking, electrostatic interaction, and hydrophobic force, exhibiting enhanced photostability of ICG and outstanding reactive oxygen species(ROS) generation ability. Moreover, significant inhibition of tumor growth by the synergetic effect of phototherapy and chemotherapy is verified in a subcutaneous4T1 tumors model. In conclusion, this work not only presents a facile and green approach to manufacture carrier-free nanodrugs, but also establishes a universal platform that has potential application in the co-delivery of near-infrared dye and hydrophobic molecules.

关键词： Metal ions J-aggregates Combination therapy

Regulation of RDN on Th1/ILC1 cell imbalance in HFMD patients caused by EV71 infection

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Chinese Journal of Natural Medicines 2021年第3期19卷 205-211页

作者： WANG Yi-Meng TIAN Ye LI Qian-Wen BIAN Zheng-Ying GAO Yue ZEN Yu TANG Lei TANG Tie-Jun GUO Wei YAO Wen-Bing jiangsu key laboratory of druggability of biopharmaceuticals School of Life Science and TechnologyChina Pharmaceutical UniversityNanjing 210009China Children’s Hospital of Nanjing Medical University Nanjing 210009China

Enterovirus 71(EV71)infection is more likely to cause hand,foot and mouth disease(HFMD)in children,which can lead to neurogenic complications and higher *** a commonly used clinical medicine,Reduning injection(RDN)helps to shorten the symptoms of patients with HFMD and facilitate the early recovery of ***,the regulatory mechanism of RDN on the HFMD immune system disorder caused by EV71 remains to be *** study collected detailed treatment data of56 children with HFMD who entered the affiliated Children’s Hospital of Nanjing Medical University during *** analysis of clinical data showed that the symptoms of the RDN treatment group were improved compared with the untreated *** explore its mechanism,the relevant detection indicators were detected by flow cytometry,enzyme-linked immunosorbent assay and realtime quantitative *** was found that the number and function of innate immune(ILCs)and adaptive immunity(Th1,Th2 and secreted cytokines)were reduced,suggesting that RDN plays a role by regulating cellular *** in vitro differentiation inhibition test further confirmed that RDN affected Th1 differentiation by inhibiting the expression of transcription factors on the basis of Th1 cell differentiation in vitro.

关键词： Enterovirus 71(EV71) Hand,foot and mouth disease(HFMD) Reduning injection(RDN) Th1 differentiated in vitro Innate immunity

Recent advances of long noncoding RNAs involved in the development of multiple sclerosis

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Chinese Journal of Natural Medicines 2020年第1期18卷 36-46页

作者： LI Qian-Wen LEI Wen CHEN Cong GUO Wei School of Life Science and Technology China Pharmaceutical UniversityJiangsu Key Laboratory of Druggability of BiopharmaceuticalsNanjing 210009China jiangsu Province Hospital of Chinese Medicine Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029China

Given the rapid increase of patients with autoimmune diseases and the lack of satisfactory therapies,the discovery of novel and effective therapeutic targets have been in an urgent *** studies have revealed that long noncoding RNAs(lncRNAs)play crucial roles in the development of multiple sclerosis(MS),which provides a new opportunity of uncovering novel mechanism associated with the progression of *** review highlights the dysregulation of lncRNAs in the development of MS in patients and animal ***,the potential clinical relevance of lncRNAs severed as therapeutic targets and diagnostic markers are discussed.

关键词： Multiple sclerosis Long noncoding RNA Experimental autoimmune encephalomyelitis Clinical relevance Dysregulation

Recent progress in tumor photodynamic immunotherapy

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Chinese Chemical Letters 2020年第7期31卷 1709-1716页

作者： Lijun Shen Tianjiao Zhou Yatong Fan Xin Chang Yi Wang Jianguo Sun Lei Xing Hulin Jiang State key laboratory of Natural Medicines Department of PharmaceuticsChina Pharmaceutical UniversityNanjing 210009China jiangsu key laboratory of druggability of biopharmaceuticals China Pharmaceutical UniversityNanjing 210009China jiangsu key laboratory of Drug Screening China Pharmaceutical UniversityNanjing 210009China jiangsu key laboratory of Drug Discovery for Metabolic Diseases China Pharmaceutical UniversityNanjing 210009China key Lab of Drug Metabolism and Pharmacokinetics State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 210009China

Photodynamic therapy(PDT)is a promising alternative approach for effective cancer treatment,which can directly destroy local tumor cells due to the generation of cytotoxic singlet oxygen and reactive oxygen species(ROS)in the tumor ***,PDT-mediated cell death is also associated with anti-tumor immune *** r,immunosuppre s sion of tumor microe nvironment is able to limit the immune response induced by PDT,it is therefore necessary to combine with immunocheckpoint inhibitor and immunoadjuvant for synergistic treatment of ***,the recent advances of PDT,immunotherapy,and photodynamic immunotherapy are reviewed.

关键词： Cancer therapy Photodynamic therapy Immunotherapy Reactive oxygen species Singlet oxygen

VHL-1 inactivation and mitochondrial antioxidants rescue C. elegans dopaminergic neurodegeneration

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Protein & Cell 2019年第8期10卷 610-614页

作者： Song Chen Shuo Luo Zhe Zhang Dengke K. Ma Cardiovascular Research Institute and Department of Physiology University of California San Francisco (UCSF) San Francisco CA 94158 USA jiangsu key laboratory of druggability of biopharmaceuticals State Key Laboratory of Natural Medicines School of Life Science and Technology China Pharmaceutical University Nanjing 210009 China

Dear Editor, Mitochondrial complex I is important for cellular ATP producti on by tran sporti ng electro ns and gen erati ng proton gradient across the mitochondrial inner membrane (Hirst, 2013). It is also a major cellular locus where electron leakage to oxygen produces superoxide, an ROS (reactive oxygen species), particularly under oxidative stress conditions. Dysfunctional complex I contributes to the most comm on oxidative phosphorylation disorder in humans, with many iden tified gen etic mutati ons in complex I sub units causing a variety of human disorders including Leigh syndrome, encephalomyopathy, cardiomyopathy, parkinsonism and hereditary optic neuropathy (Hirst, 2013;Guo et al., 2017). In addition, complex I is the major target of many parkinsonismcausing neurotoxins including rotenone and MPTP. Past biochemical, cell biological and structural studies have elucidated how complex I functions normally in mitochondrial respiration (Hirst, 2013;Guo et al., 2017;Letts and Sazanov, 2017). Nonetheless, our understanding of mechanisms how complex I dysfunction leads to human diseases is far from completion;therapeutic targets and strategies are urgently needed.

关键词： VHL-1 inactivation mitochondrial antioxidants neurodegeneration

Populational change of CD4^(+)CD25^(+)Treg cells is responsible for the synergistic effect of the combination of RAMP2 with baicalin in treating recurrent spontaneous abortion mouse models

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Traditional Medicine Research 2024年第8期9卷 59-66页

作者： Cong Chen Zhuo-Lan Li Jing-Tian Guo Wen-Yao Xue Wei Guo Department of Gynecology Jiangsu Province Hospital of Chinese MedicineAffiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029China jiangsu key laboratory of druggability of biopharmaceuticals State Key Laboratory of Natural MedicinesSchool of Life Science and TechnologyChina Pharmaceutical UniversityNanjing 211198China

Background: The absence of a safe and effective therapy for recurrent spontaneous abortion due to a maternofetal failure in immunological tolerance remains an intractable clinical obstacle for surgeons. Recently, traditional Chinese medicine has become a feasible alternative for certain diseases, including recurrent spontaneous abortion. However, because of the complex composition of the traditional Chinese medicine formula, its action mechanism remains unclear. Methods: We selected two isolated active ingredients (RAMP and baicalin) from the traditional Chinese medicine formula and used an abortion-prone CBA/J × DBA/2 model to simulate human RSA and compared the changes in fetal resorption rate, Treg cell percentage, and relevant cytokines before and after combination therapy. In addition, The mechanisms were preliminarily discussed using in vitro differentiation models. Results: In CBA/J × DBA/2 abortion-prone mice, the combination therapy resulted in a lower embryo resorption rate compared to that obtained with individual delivery of either RAMP or baicalin, thereby playing an embryo-protective role through the increase in Treg cells for the maintenance of maternal-fetal immune tolerance. In in vitro primary cell differentiation experiments, the concentration of Treg cells significantly increased from 11% to 17.9% after the combination therapy compared to that of the single administration group. Conclusion: the synergistic effects of RAMP and baicalin were responsible for Treg differentiation. The present study provides a solid basis for improving the applicability of traditional Chinese herbs in the treatment of recurrent spontaneous abortion.

关键词： recurrent spontaneous abortion Atractylodes macrocephala Koidz. Scutellaria baicalensis Georgi CBA/J×DBA/2 regulatory T cells

Polysaccharide Nanodrug Improving the Combination Therapy of Chemo-and Antiangiogenic Therapy through pH-Triggered Drug Delivery

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Polysaccharide Nanodrug Improving the Combination Therapy of...

Multifunctional peptides-hydroxyapatite hybrid nanoparticles for metastatic cancer combination therapy

2018年第十二届中国药物制剂大会

作者： Hui Xiong Yuanyuan Wu 姚静 State key Laborary of Natural Medicine and jiangsu key laboratory of druggability of biopharmaceuticals Department of Pharmaceutics China Pharmaceutical University

＜正＞Combination of chemotherapy and antiangiogenesis holds vast promise for cancer *** previous study proved that covalently connecting cytotoxic ursolic acid（UOA）to low molecular weight heparin（LMWH）with anti-angiogenesis activities through non-sensitive amido bond linker could develop polysaccharide conjugates-based nanodrugs（LMWH-UA）,which could significantly improve tumoricidal efficiency through achieving chemo/antiangiogenic combination *** order to further investigate

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Multifunctional peptides-hydroxyapatite hybrid nanoparticles...