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Targeted anti-tumor synergistic effects of Myc decoy oligodeoxynucleotides-loaded selenium nanostructure combined with chemoradiotherapy on LNCaP prostate cancer cells

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Oncology Research 2024年第1期32卷 101-125页

作者： ROGHAYEH GHORBANI MAHMOUD GHARBAVI ALI SHARAFI ELHAM RISMANI HAMED REZAEEJAM YOUSEF MORTAZAVI BEHROOZ JOHARI Department of Medical biotechnology School of MedicineZanjan University of Medical SciencesZanjanIran Nanotechnology Research center Ahvaz Jundishapur University of Medical SciencesAhvazIran Zanjan pharmaceutical biotechnology Research center Zanjan University of Medical SciencesZanjanIran Department of pharmaceutical biotechnology School of PharmacyZanjan University of Medical SciencesZanjanIran Molecular Medicine Department Biotechnology Research CenterPasteur Institute of IranPasteur AvenueTehranIran Department of Radiology Technology School of Allied Medical SciencesZanjan University of Medical SciencesZanjanIran

In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer cells.Myc decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics assays.ODNs were loaded on the synthesized Se@BSA@Chi-MTX nanostructure.The physicochemical characteristics of nanostructures were determined by FTIR,DLS,UV-vis,TEM,EDX,in vitro release,and hemolysis tests.Subsequently,the cytotoxicity properties of them with and without X-irradiation were investigated by uptake,MTT,cell cycle,apoptosis,and scratch assays on the LNCaP cell line.The results of DLS and TEM showed negative charge(−9 mV)and nanometer size(40 nm)for Se@BSA@Chi-DEC-MTX NPs,respectively.The results of FTIR,UV-vis,and EDX showed the proper interaction of different parts and the correct synthesis of nanoparticles.The results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/mL.The ODNs release from the nanostructures showed a pH-dependent manner,and the release rate was 15%higher in acidic pH.The targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen(PSMA).The significant synergistic effects of nanostructure(containing MTX drug)treatment along with X-irradiation showed cell growth inhibition,apoptosis induction(~57%),cell cycle arrest(G2/M phase),and migration inhibition(up to 90%)compared to the control.The results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP cells.This nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.

关键词： Chemoradiotherapy Combination therapy Decoy oligodeoxynucleotides Myc transcription factor Selenium nanoparticle Prostate cancer

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A sustainable process to 100%bio-based nylons integrated chemical and biological conversion of lignocellulose

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Green Energy & Environment 2024年第2期9卷 390-402页

作者： Ruijia Hu Ming Li Tao Shen Xin Wang Zhuohua Sun Xinning Bao Kequan Chen Kai Guo Lei Ji Hanjie Ying Pingkai Ouyang Chenjie Zhu College of biotechnology and pharmaceutical Engineering Nanjing Tech UniversityNanjingChina National Engineering Research center for biotechnology Nanjing Tech UniversityNanjingChina Beijing Key Laboratory of Lignocellulosic Chemistry Beijing Forestry UniversityBeijingChina

Considerable progress has been made in recent years to the development of sustainable polymers from bio-based feedstocks.In this study,100%bio-based nylons were prepared via an integrated chemical and biological process from lignocellulose.These novel nylons were obtained by the melt polymerization of 3-propyladipic acid derived from lignin and 1,5-pentenediamine/1,4-butanediamine derived from carbohydrate sugar.Central to the concept is a three-step noble metal free catalytic chemical funnelling sequence(Raney Ni mediated reductive catalytic fractionation-reductive funnelling-oxidative funnelling),which allowed for obtaining a single component 3-propyladipic acid from lignin with high efficiency.The structural and thermodynamic properties of the obtained nylons have been systematically investigated,and thus obtained transparent bio-based nylons exhibited higher Mw(>32,000)and excellent thermal stability(Td5%>265℃).Considering their moderate Tg and good melt strength,these transparent bio-based nylons could serve as promising functional additives or temperature-responsive materials.

关键词： Lignocellulose Lignin Reductive catalytic fractionation Bio-based nylon

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Pharmacological effects of volatile oil from chrysanthemum and its associated mechanisms:a review

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Acupuncture and Herbal Medicine 2024年第1期4卷 79-91页

作者： Jing Zhang Weiqiang Su Nina Filipczak Ying Luo Anping Wan Yao He Shijuan Yan Xiang Li Ming Yang Key Laboratory of Modern Preparation of TCM Ministry of EducationJiangxi University of Chinese MedicineNanchangChina center for pharmaceutical biotechnology and nanomedicine Northeastern UniversityBostonUSA National pharmaceutical Engineering center for Solid Preparation in Chinese Herbal Medicine Jiangxi University of Chinese MedicineJiangxi University of Chinese MedicineNanchangChina

Volatile oil(VO)is the main chemical component of common plants in Chrysanthemum genus,and it possesses several beneficial pharmacological properties,including bacteriostatic,antioxidant,anti-tumor,anti-inflammatory,antipyretic,analgesic,antiosteoporotic,antihypertensive,sedative,and hypnotic effects.To date,research on the effective components of Chrysanthemum extract has mainly focused on flavonoids,whereas limited data are available on the chemical constituents and underlying mechanisms of action of the VO components.In this review,the pharmacological activities and mechanisms of VO are comprehensively reviewed with the aim of providing a foundation for further development for medicinal,aromatherapy,and diet therapy applications.

关键词： Action mechanisms Chrysanthemum Pharmacological activity Volatile oil

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Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

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Oncology Research 2024年第2期32卷 309-323页

作者： BEHROOZ JOHARI MILAD PARVINZAD LEILAN MAHMOUD GHARBAVI YOUSEF MORTAZAVI ALI SHARAFI HAMED REZAEEJAM Department of Medical biotechnology School of MedicineZanjan University of Medical SciencesZanjanIran Zanjan pharmaceutical biotechnology Research center Zanjan University of Medical SciencesZanjanIran Nanotechnology Research center Ahvaz Jundishapur University of Medical SciencesAhvazIran Department of Radiology Technology School of Allied Medical SciencesZanjan University of Medical SciencesZanjanIran

The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.

关键词： Combinational therapy Antisense therapy Myc signaling pathway Niosomes Radiation therapy SeNPs

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Ce6 nanoassemblies:Molecular mechanism and strategies for combinational anticancer therapy Special Collection:Aggregation-Induced Processes and Functions

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Aggregate 2024年第1期5卷 130-147页

作者： Yuwei Liu Shuting Xu Qingyang Lyu Yi Huang Weiping Wang State Key Laboratory of pharmaceutical biotechnology The University of Hong KongHong KongChina Department of Pharmacology and Pharmacy Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina Laboratory of Molecular Engineering and nanomedicine Dr.Li Dak-Sum Research CentreThe University of Hong KongHong KongChina

Nowadays,cancer has become the leading cause of death worldwide,driving the need for effective therapeutics to improve patient prognosis.Photodynamic therapy(PDT)has been widely applied as an antitumor modality,owing to its minimal invasiveness,localized tumor damage,and high safety profile.However,its efficacy is limited by poor stability of photosensitizers,inadequate tumor accumulation,and a complex tumor microenvironment.To overcome these challenges,extensive endeavors have been made to explore the co-assembly of the widely used photosensitizer chlorin e6(Ce6)with various functional small molecules to enhance pharmacodynamic activity.This review provides a comprehensive overview of current studies on Ce6-based nanoparticles for effective PDT and precise delivery of functional molecules.The self-assembly mechanism will be discussed in detail,with a focus on potential strategies for combinational therapy with PDT.

关键词： cancer treatment carrier-free chlorin e6(Ce6) light nanomedicine photodynamic therapy(PDT) selfassembly

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Development of an active-site titrant for SARS-CoV-2 main protease as an indispensable tool for evaluating enzyme kinetics

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2349-2357页

作者： Rabea Voget Julian Breidenbach Tobias Claff Alexandra Hingst Katharina Sylvester Christian Steinebach Lan Phuong Vu Renato H.Weiße Ulrike Bartz Norbert Sträter Christa E.Müller Michael Gütschow pharmaceutical Institute Pharmaceutical&Medicinal ChemistryUniversity of BonnBonn 53121Germany Institute of Bioanalytical Chemistry Center for Biotechnology and BiomedicineLeipzig UniversityLeipzig 04103Germany Department of Natural Sciences University of Applied Sciences Bonn-Rhein-SiegRheinbach 53359Germany

A titrant for the SARS-CoV-2 main protease(M^(pro))was developed that enables,for the first time,the exact determination of the concentration of the enzymatically active M^(pro) by active-site titration.The covalent binding mode of the tetrapeptidic titrant was elucidated by the determination of the crystal structure of the enzyme–titrant complex.Four fluorogenic substrates of M^(pro),including a prototypical,internally quenched Dabcyl-EDANS peptide,were compared in terms of solubility under typical assay conditions.By exploiting the new titrant,key kinetic parameters for the M^(pro)-catalyzed cleavage of these substrates were determined.

关键词： COVID-19 SARS-CoV-2 Main protease Peptide nitriles Fluorogenic substrates Active-site titration X-ray crystallography Inner filter effect

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Understanding the Novel Approach of Nanoferroptosis for Cancer Therapy

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Nano-Micro Letters 2024年第9期16卷 501-556页

作者： Afsana Sheikh Prashant Kesharwani Waleed H.Almalki Salem Salman Almujri Linxin Dai Zhe‑Sheng Chen Amirhossein Sahebkar Fei Gao Department of Pharmaceutics School of Pharmaceutical Education and ResearchJamia HamdardNew Delhi 110062India Department of Pharmacology and Toxicology Faculty of PharmacyUmm Al-Qura UniversityMakkahSaudi Arabia Department of Pharmacology College of PharmacyKing Khalid University61421 Asir‑AbhaSaudi Arabia State Key Laboratory of Southwestern Chinese Medicine Resources Pharmacy SchoolChengdu University of Traditional Chinese MedicineChengdu 611130People’s Republic of China Department of pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityNew York 11439USA biotechnology Research center Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran Applied Biomedical Research center Mashhad University of Medical SciencesMashhadIran

As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells.Due to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting.This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis.Additionally,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.

关键词： Ferroptosis Nanoparticles Ferrotherapy Cancer Genes Nanotechnology Toxicity Reactive oxygen species

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A Robust N-Terminal Pro-Brain Natriuretic Peptide Assay for Clinical Diagnosis of Heart Failure in Elderly Patients

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Journal of Analysis and Testing 2024年第1期8卷 74-82页

作者： Xue Gong Jiangling Wu Jiajia Zhang Zhongwei Jiang Yi Wang Pu Zhang Engineering Research center for biotechnology of Active Substances(Ministry of Education) Chongqing Key Laboratory of Green Synthesis and ApplicationsCollege of ChemistryChongqing Normal UniversityChongqing 401331China Chongqing Research center for pharmaceutical Engineering College of PharmacyChongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory University Town Hospital of Chongqing Medical UniversityChongqing 401331China

Heart failure(HF)is a clinical hallmark of cardiovascular syndrome leading to substantial morbidity,repeated hospitalization,and enormous healthcare expenditure.As elderly populations continue to increase,biomarker-guided diagnosis and treatment for age-related cardiac decline have become essential.Accumulating evidence demonstrates that N-terminal proBNP(NT-proBNP)can provide a unique window into the diagnosis and risk stratification with HF.Herein,a simple yet robust aptasensor is developed for on-site recognizing the NT-proBNP by its targeting aptamer,thus achieving the accurate diagnosis of HF.This aptasensing system is prepared by absorbing the fluorophore-labeled aptamer strand onto the graphene oxide(GO),leading to efficient quenching without possible off-site signal leakage.The aptamer strand can specifically identify target NT-proBNP molecules via a versatile conformational transformation,resulting in the desorption of the aptamer-NTproBNP complexes from GO and re-generation fluorescence signal,thus allowing sensitive detection of NT-proBNP in 37 clinical blood samples.Taking advantage of the high specificity of aptamer-guaranteed recognitions of NT-proBNP,this aptasensor system readily achieves better diagnostic performance for HF than commercially adopted chemiluminescence immunoassay(Siemens,CLIA)in hospitals in terms of accuracy(89.2%vs 83.8%),specificity(89.5%vs 84.2%),and positive predictive value(88.9%vs 83.3%).This work provides a stable option for the diagnosis and treatment of elderly HF-related diseases inclinics.

关键词： NT-proBNP Graphene oxide Aptamer Heart failure Clinical diagnosis

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Tumor microenvironment reprogramming by nanomedicine to enhance the effect of tumor immunotherapy

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Asian Journal of pharmaceutical Sciences 2024年第2期19卷 1-37页

作者： Yu Huang Hui Fan Huihui Ti School of Chinese Materia Medica Guangdong Pharmaceutical UniversityGuangzhou 510006China Guangdong Province Precise Medicine Big Date of Traditional Chinese Medicine Engineering Technology Research center Guangdong Pharmaceutical UniversityGuangzhou 510006China School of Pharmacy Guangdong Pharmaceutical UniversityGuangzhou 510006China

With the rapid development of the fields of tumor biology and immunology, tumor immunotherapy has been used in clinical practice and has demonstrated significant therapeutic potential, particularly for treating tumors that do not respond to standard treatment options. Despite its advances, immunotherapy still has limitations, such as poor clinical response rates and differences in individual patient responses, largely because tumor tissues have strong immunosuppressive microenvironments. Many tumors have a tumor microenvironment (TME) that is characterized by hypoxia, low pH, and substantial numbers of immunosuppressive cells, and these are the main factors limiting the efficacy of antitumor immunotherapy. The TME is crucial to the occurrence, growth, and metastasis of tumors. Therefore, numerous studies have been devoted to improving the effects of immunotherapy by remodeling the TME. Effective regulation of the TME and reversal of immunosuppressive conditions are effective strategies for improving tumor immunotherapy. The use of multidrug combinations to improve the TME is an efficient way to enhance antitumor immune efficacy. However, the inability to effectively target drugs decreases therapeutic effects and causes toxic side effects. Nanodrug delivery carriers have the advantageous ability to enhance drug bioavailability and improve drug targeting. Importantly, they can also regulate the TME and deliver large or small therapeutic molecules to decrease the inhibitory effect of the TME on immune cells. Therefore, nanomedicine has great potential for reprogramming immunosuppressive microenvironments and represents a new immunotherapeutic strategy. Therefore, this article reviews strategies for improving the TME and summarizes research on synergistic nanomedicine approaches that enhance the efficacy of tumor immunotherapy.

关键词： Tumor immunotherapy Tumor micr oenvir onment nanomedicine Tumor repr ogramming

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Network Pharmacology of Xian-Lian-Jie-Du Decoction in Ameliorating Colorectal Cancer

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World Journal of Traditional Chinese Medicine 2024年第1期10卷 83-92页

作者： Ming-Xia Zhao Cheng-Lin Song Qin-Chang Zhang Hao-Jie Du Shu-Qiong Zhang Yu-Xian Shen Yang Sun Hai-Bo Cheng Wen Lv Department of Pharmacy School of Basic Medical SciencesAnhui Medical UniversityHefeiAnhuiChina Department of Biopharmaceutical Research Institute Anhui Medical UniversityHefeiAnhuiChina Department of pharmaceutical Analysis State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijingChina Jiangsu Collaborative Innovation center of Traditional Chinese Medicine in Prevention and Treatment of Tumor First Clinical CollegeNanjing University of Chinese MedicineNanjingJiangsuChina Deparment of biotechnology and pharmaceutical Sciences State Key Laboratory of Pharmaceutical BiotechnologySchool of Life SciencesNanjing UniversityNanjingJiangsuChina Deparment of Gynecology Institute of Traditional Chinese Medicine of Zhejiang ProvinceTongde Hospital of Zhejiang ProvinceHangzhouZhejiangChina

Objective:In this study,we screened for therapeutic targets of the Xian-Lian-Jie-Du decoction(XLJDD)for colorectal cancer(CRC)and explored the underlying mechanisms using network pharmacology techniques.Methods:Genes associated with CRC were collected from the Gene Cards database.The names of the active compounds of XLJDD were used as keywords in the“chemical name”in the Traditional Chinese Medicine Systems Pharmacology(TCMSP)database to search the targets.The protein-protein interaction(PPI)network was constructed using Cytoscape 3.8.1.Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to identify key target proteins.Results:A total of 234 XLJDD-related targets and 250 cross-targets between XLJDD and CRC were collected based on the TCMSP and HIT 2.0 databases.A PPI network constructed based on the STRING database revealed interactions for all 250 proteins.The network results revealed TP53,MYC,CCND1,AKT1,CASP3,and STAT3 as core potential targets.KEGG pathway analysis of the 250 potential XLJDD targets for CRC in the Metascape database was performed using RStudio software.The top 12 gene ratio aggregated analysis results were visualized in bubble charts.The interleukin(IL)-17 signaling pathway had the highest correlation with the tumor necrosis factor(TNF)signaling pathway.Conclusions:XLJDD may be effective in ameliorating CRC by controlling inflammatory factors related to the IL-17 and TNF pathways and targeting proto-oncogenes and tumor suppressor genes,including MYC,CCND1,CTNNB1,and TP53.

关键词： Colorectal cancer network pharmacology Xian-Lian-Jie-Du decoction

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