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A nanoagent for concurrent therapy of breast cancer bone metastasis and cancer-induced bone pain through SLC7A11 interruption and photodynamic therapy

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Chinese Chemical Letters 2024年第2期35卷 295-299页

作者： Qi Fu Zhongming Lian Mengya Niu Yaru Huang Yanqiu Ai Long He Dandan Zhang Cuixia Zheng Jian-Jun Yang Lei Wang Dandan Tian Department of Anesthesiology Pain and Perioperative MedicineThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450001China School of pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China Translational Medical Center of Huaihe Hospital Henan UniversityKaifeng 475004China Key Laboratory of Advanced Drug preparation Technologies Ministry of EducationSchool of Pharmaceutical SciencesZhengzhou UniversityZhengzhou 450001China

Bone metastasis,a life-threatening complication of advanced breast cancer,is often accompanied by debilitating pain(cancer-induced bone pain,CIBP)that severely impairs life quality and survival.The concurrent treatment of bone metastases and CIBP remains a clinical challenge because the therapeutic options are limited.In this study,we construct a near-infrared light-activated nano-therapeutic system to meet this conundrum.In detail,sorafenib(SRF)and photosensitizer(chlorin e6,Ce6)are encapsulated into mesoporous hydroxyapatite nanoparticles(HANPs),which are further functionalized with hyaluronic acid(HA)to obtain HA-SRF/Ce6@HANPs system.The designed nanoplatform destroys tumor cells in vitro and in vivo via the synergism of SRF(interrupting the exchange of cystine/glutamate by inhibiting SLC7A11)and photodynamic therapy(PDT,inducing reactive oxygen species generation).The decrease in tumor burden and reduction of extracellular glutamate significantly attenuate CIBP in mice model with developing bone cancer.Moreover,the combination of HA-SRF/Ce6@HANPs and PDT inhibit osteoclasts activation,promote osteoblast differentiation and accelerate bone repair.Overall,the nanoagent with good biocompatibility may provide an effective therapy method for the concurrent treatment of breast cancer bone metastasis and CIBP.

关键词： Breast cancer bone metastasis Cancer-induced bone pain Cystine/glutamate antiporter Sorafenib Photodynamic therapy

Strategies that regulate LSD1 for novel therapeutics

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1494-1507页

作者： Meng Li Mengge Dai Bing Cheng Shaotong Li Enhui Guo Junwei Fu Ting Ma Bin Yu School of pharmaceutical Sciences&Key Laboratory of Advanced Drug preparation Technologies Ministry of EducationZhengzhou UniversityZhengzhou 450001China College of Chemistry Zhengzhou UniversityZhengzhou 450001China Tianjian Laboratory of Advanced Biomedical Sciences Institute of Advanced Biomedical SciencesZhengzhou UniversityZhengzhou 450000China Pingyuan Laboratory State Key Laboratory of Antiviral DrugsHenan Normal UniversityXinxiang 453007China State Key Laboratory of pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Histone methylation plays crucial roles in regulating chromatin structure and gene transcrip-tion in epigenetic modifications.Lysine-specific demethylase 1(LSD1),the first identified histone de-methylase,is universally overexpressed in various diseases.LSD1 dysregulation is closely associated with cancer,viral infections,and neurodegenerative diseases,etc.,making it a promising therapeutic target.Several LSD1 inhibitors and two small-molecule degraders(UM171 and BEA-17)have entered the clinical stage.LSD1 can remove methyl groups from histone 3 at lysine 4 or lysine 9(H3K4 or H3K9),resulting in either transcription repression or activation.While the roles of LSD1 in transcrip-tional regulation are well-established,studies have revealed that LSDl can also be dynamically regulated by other factors.For example,the expression or activity of LSD1 can be regulated by many proteins that form transcriptional corepressor complexes with LSD1.Moreover,some post-transcriptional modifica-tions and cellular metabolites can also regulate LSD1 expression or its demethylase activity.Therefore,in this review,we will systematically summarize how proteins involved in the transcriptional corepressor complex,various post-translational modifications,and metabolites act as regulatory factors for LSD1 ac-tivity.

关键词： LSD1 regulation Transcription repression Transcription activation the Corepressor complex Post-transcriptional modifications Metabolites

New phenylbutenoids and terpene glycosides from Ginkgo biloba leaves

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Chinese Journal of Natural Medicines 2024年第2期22卷 161-170页

作者： SUN Zeshi LIN Shan WU Zhi-Li DONG Hong-Yuan XU Xi-Ke LI Hui-Liang WANG Jinxin School of Pharmacy Second Military Medical UniversityShanghai 200433China State Key Laboratory of New Drug and pharmaceutical Process Shanghai Institute of Pharmaceutical IndustryChina State Institute of Pharmaceutical IndustryShanghai 201203China

Our continued works on the chemical constituents of Ginkgo biloba(G.biloba)leaves has led to the isolation of two novel phenylbutenoids(1,2),along with five previously unidentified terpene glycosides(3−7).Among them,compounds 1 and 2 represent unique(Z)-phenylbutenoids,3−6 are megastigmane glycosides,and 7 is identified as a rare bilobanone glycoside(Fig.1).This study marks the first reported isolation of phenylbutenoid and bilobanone glycoside from G.biloba.The chemical structures of these compounds were elucidated through extensive spectroscopic analysis,including HR-ESI-MS and various 1D and 2D NMR experiments.Furthermore,the absolute configurations of these molecules were determined using Mosher’s method,ECD experiments,and Cu-KαX-ray crystallographic analyses.

关键词： Ginkgo biloba Phenylbutenoid Megastigmane glycoside Bilobanone glycoside

Bioinspired zinc-mediated umpolung thiolation of alkyl electrophiles: reaction development, scope and mechanism

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Science China Chemistry 2024年第3期67卷 898-907页

作者： Yuenian Xu Yan Zhang Yong Liu Wen-Wu Sun Jie Huang Hui He Yingjie Wu Wen Liu Shao-Fei Ni Xu-Qiong Xiao Xinxin Shao College of Material Chemistry and Chemical EngineeringKey Laboratory of Organosilicon Chemistry and Material Technology of Ministry of EducationHangzhou Normal UniversityHangzhou 311121China School of pharmaceutical Sciences South-Central Minzu UniversityWuhan 430074China Department of Chemistry and Key Laboratory for preparation and Application of Ordered Structural Materials of Guang-dong Province Shantou UniversityShantou 515063China

Zinc-promoted umpolung thiolation of alkyl electrophiles with masked sulfur transfer reagents in the absence of nickel or copper catalysis is described. This protocol proceeds via a SET process of Zn to electrophilic sulfur reagent followed by insertion of Zn into disulfide and nucleophilic thiolation, providing straightforward access to a wide range of alkyl sulfides with broad substrate scope. A neutral TMEDA-ligated four-coordinated zinc thiolate with tetrahedra geometry was synthesized, isolated and fully characterized by NMR, IR and X-ray analysis. More importantly, the chemical reactivity of this active intermediate has been investigated, enabling the construction of C-Se, C-Te, Sb-S and Bi-S bonds to prepare valuable sulfur-containing molecules and beyond.

关键词： umpolung thiolation C(sp^(3))-S bond formation masked sulfur reagents reductive coupling

Multifunctional nanoparticle-mediated combining therapy for human diseases

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Signal Transduction and Targeted Therapy 2024年第2期9卷 343-375页

作者： Xiaotong Li Xiuju Peng Makhloufi Zoulikha George Frimpong Boafo Kosheli Thapa Magar Yanmin Ju Wei He School of Pharmacy China Pharmaceutical UniversityNanjing 2111198PR China Xiangya School of pharmaceutical Sciences Central South UniversityChangsha 410013PR China Shanghai Skin Disease Hospital Tongji University School of MedicineShanghai 200443China

Combining existing drug therapy is essential in developing new therapeutic agents in disease prevention and treatment.In preclinical investigations,combined effect of certain known drugs has been well established in treating extensive human diseases.Attributed to synergistic effects by targeting various disease pathways and advantages,such as reduced administration dose,decreased toxicity,and alleviated drug resistance,combinatorial treatment is now being pursued by delivering therapeutic agents to combat major clinical illnesses,such as cancer,atherosclerosis,pulmonary hypertension,myocarditis,rheumatoid arthritis,inflammatory bowel disease,metabolic disorders and neurodegenerative diseases.Combinatorial therapy involves combining or co-delivering two or more drugs for treating a specific disease.Nanoparticle(NP)-mediated drug delivery systems,i.e.,liposomal NPs,polymeric NPs and nanocrystals,are of great interest in combinatorial therapy for a wide range of disorders due to targeted drug delivery,extended drug release,and higher drug stability to avoid rapid clearance at infected areas.This review summarizes various targets of diseases,preclinical or clinically approved drug combinations and the development of multifunctional NPs for combining therapy and emphasizes combinatorial therapeutic strategies based on drug delivery for treating severe clinical diseases.Ultimately,we discuss the challenging of developing NP-codelivery and translation and provide potential approaches to address the limitations.This review offers a comprehensive overview for recent cutting-edge and challenging in developing NP-mediated combination therapy for human diseases.

关键词： drugs diseases prevention

Cancer cell membrane-coated bacterial ghosts for highly efficient paclitaxel delivery against metastatic lung cancer

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Acta Pharmaceutica Sinica B 2024年第1期14卷 365-377页

作者： Dandan Ling Xueli Jia Ke Wang Qiucheng Yan Bochuan Yuan Lina Du Miao Li Yiguang Jin Anhui Medical University Hefei 230032China Department of pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer,although it is limited by the low tumor delivery efficacy of anticancer drugs.Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect;however,excessively generated immunogenicity will cause serious inflammatory response syndrome.Here,we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts(LP@BG@CCM)by layer-by-layer encapsulation for the treatment of metastatic lung cancer.The preparation processes were simple,only involving film formation,electroporation,and pore extrusion.LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells.In the 4T1 breast cancer metastatic lung cancer mouse models,the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance,the reduced lung weight,the clear lung tissue structure,and the enhanced cancer cell apoptosis compared to its precursors.Moreover,several major immune factors were improved after administration of LP@BG@CCM,including the CD4^(+)/CD8a^(+)T cells in the spleen and the TNF-α,IFN-γ,and IL-4 in the lung.LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy,which is a promising medication for the treatment of metastatic lung cancer.

关键词： Apoptosis Bacterial ghost Cancer cell membrane Immune stimulation Liposome Lung targeting Metastatic lung cancer Paclitaxel

Visualization of nasal powder distribution using biomimetic human nasal cavity model

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Acta Pharmaceutica Sinica B 2024年第1期14卷 392-404页

作者： Jiawen Su Yan Liu Hongyu Sun Abid Naeem Huipeng Xu Yue Qu Caifen Wang Zeru Li Jianhua Lu Lulu Wang Xiaofeng Wang Jie Wu Lixin Sun Jiwen Zhang Zhigang Wang Rui Yang Li Wu Key Laboratory of Modern preparation of TCM Ministry of EducationJiangxi University of Chinese MedicineNanchang 330004China Key Laboratory of Molecular Pharmacology and Drug Evaluation School of PharmacyMinistry of EducationYantai UniversityYantai 264005China Shanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201210China Nantong Haimen People’s Hospital Nantong 226199China Yangtze Delta Drug Advanced Research Institute Nantong 226126China Shenyang pharmaceutical University Shenyang 110016China National Institutes for Food and Drug Control Beijing 100000China Nanjing University of Chinese Medicine Nanjing 210023China

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity.However,no reliable method is currently available to assess its impact on delivery performance.In this study,a biomimetic nasal model based on three-dimensional(3D)reconstruction and three-dimensional printing(3DP)technology was developed for visualizing the deposition of drug powders in the nasal cavity.The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females.The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test.The experimental device produced the most satisfactory results with five spray times.Furthermore,particle sizes and spray angles were found to significantly affect the experimental device’s performance and alter drug distribution,respectively.Additionally,mometasone furoate(MF)nasal spray(NS)distribution patterns were investigated in a goat nasal cavity model and three male goat noses,confirming the in vitro and in vivo correlation.In conclusion,the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

关键词： Nasal drug deposition Nasal drug distribution Nasal drug delivery Biomimetic nasal model Nasal powder Three-dimensional reconstruction Three-dimensional printing Nasal drug distribution

The age of vanadium-based nanozymes: Synthesis, catalytic mechanisms, regulation and biomedical applications

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Chinese Chemical Letters 2024年第4期35卷 52-60页

作者： Shuaiwen Li Zihui Chen Feng Yang Wanqing Yue Department of Chemistry Key Laboratory of Biomedical Functional MaterialsSchool of ScienceChina Pharmaceutical UniversityNanjing 211198China Key Laboratory of Drug Quality Control and Pharmacovigilance(China pharmaceutical University) Ministry of EducationNanjing 211198China

Nanomaterials with enzyme-mimic(nanozyme) activity have garnered considerable attention as a potential alternative to natural enzymes, thanks to their low preparation cost, high activity, ease of preservation, and unique physicochemical properties. Vanadium(V) is a transition metal that integrates the benefits of valence-richness, low cost, and non-toxicity, making it a desirable candidate for developing a range of emerging nanozymes. In this review, we provide the first systematic summary of recent research progress on V-based nanozymes. First, we summarize the preparation of V-based nanozymes using both top-down and bottom-up synthesis methods. Next, we review the mechanism of V-based nanozymes that mimic the activity of various enzymes. We then discuss methods for regulating V-based nanozyme activity, including morphology, size, valence engineering, defect engineering, external triggering, and surface engineering. Afterward, we outline various biomedical applications, including therapeutic, anti-inflammatory, antibacterial, and biosensing. Finally, we prospect the challenges and countermeasures for V-based nanozymes based on their development. By summarizing recent research progress on V-based nanozymes, we hope to provide useful insights for researchers to further explore their potential applications and overcome their existing challenges.

关键词： Vanadium Nanozymes Catalytic mechanisms Biomedical applications Regulation

Multi-functional and multi-scenario applications for MXene aerogels with synergistically enhanced asymmetric modules

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Nano Research 2024年第4期17卷 3359-3368页

作者： Junru Yao Jintang Zhou Feng Yang Guiyu Peng Yijie Liu Zhengjun Yao Fan Wu Haibo Zeng College of Materials Science and Technology Nanjing University of Aeronautics and AstronauticsNanjing 211100China Key Laboratory of Material preparation and Protection for Harsh Environment(Nanjing University of Aeronautics and Astronautics) Ministry of Industry and Information TechnologyNanjing 211100China School of Mechanical Engineering Nanjing University of Science and TechnologyNanjing 210094China

The development of multifunctional materials and synergistic applications of various functions are important conditions for integrated and miniaturized equipment.Here,we developed asymmetric MXene/aramid nanofibers/polyimides(AMAP)aerogels with different modules using an integrated molding process.Cleverly asymmetric modules(layered MXene/aramid nanofibers section and porous MXene/aramid nanofibers/polyimides section)interactions are beneficial for enhanced performances,resulting in low reflection electromagnetic interference(EMI)shielding(specific shielding effectiveness of 2483(dB·cm^(3))/g and a low R-value of 0.0138),high-efficiency infrared radiation(IR)stealth(ultra-low thermal conductivity of 0.045 W/(m·K)and IR emissivity of 0.32 at 3–5μm and 0.28 at 8–14μm),and excellent thermal management performances of insulated Joule heating.Furthermore,these multifunctional AMAP aerogels are suitable for various application scenarios such as personal and building protection against electromagnetic pollution and cold,as well as military equipment protection against infrared detection and EMI.

关键词： multifunctional material electromagnetic interference shielding low reflection infrared radiation stealth thermal insulation Joule heating