Poor solubility often results in low efficacy of antitumor drugs.Nevertheless,limited research has been conducted on the potential decrease in drug efficacy following the self-assembly of hydrophobic pure drugs into n...Poor solubility often results in low efficacy of antitumor drugs.Nevertheless,limited research has been conducted on the potential decrease in drug efficacy following the self-assembly of hydrophobic pure drugs into nanodrugs,and solutions to this problem are even rarer.Loading water-insoluble antitumor drugs into nanocarriers offers a promising solution.However,intricate carrier preparation,limited drug loading capacity,and carrier-associated safety remain key challenges.In this study,based on the discovery that hydrophobic gambogic acid(GA) self-assembles into nanostructures with diminished antitumor efficacy in aqueous environments,we developed a carrier-free nanodrug system,designated as GA-S-S-AS nanoparticles(NPs),characterized by straightforward preparation,high drug loading,fluorescence imaging,tumor-targeting,and responsive drug release in reducing environments.Specifically,the hydrophobic GA was covalently linked to the hydrophilic aptamer through a disulfide bond and then self-assembled into the nanodrugs.About 92 % of drug was encapsulated in self-assembled NPs,demonstrating remarkable stability under physiological conditions and controlled release of GA in the high-glutathione environment characteristic of tumor sites.Furthermore,by utilizing the synergistic interaction between the enhanced permeability and retention(EPR) effect and ligand-receptor active targeting mechanisms,the nanodrugs significantly increased the accumulation of GA at tumor locations.Consequently,the nanodrugs exhibited optimal therapeutic efficacy against the tumor both in vitro and in vivo,significantly inhibiting tumor growth.Furthermore,the nanodrugs demonstrated enhanced biosafety compared to free GA,effectively reducing GA-induced hepatotoxicity.Taken together,these findings underscore the significant potential of this multifunctional carrier-free nanodrugs for the targeted delivery of GA,thereby laying a foundation for future endeavors aimed at developing novel formulations of hydrophobic antitumor drugs.展开更多
Employing the principle of active moiety concatenation, a novel series of symmetrical triazine compounds were designed. A series of novel triazine compounds were synthesized using cyanuric chloride, amines, and chalco...Employing the principle of active moiety concatenation, a novel series of symmetrical triazine compounds were designed. A series of novel triazine compounds were synthesized using cyanuric chloride, amines, and chalcones as the initial reactants. The structures of these compounds were characterized through FT-IR, 1H-NMR, 13C-NMR, high-resolution mass spectrometry (HRMS) and high performance liquid chromatography (HPLC). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetra- zolium bromide (MTT) assay was employed to evaluate the in vitro anti-proliferative activity of the new s-triazine compounds against human lung cancer cells (A549), human cervical cancer cells (HeLa), human breast cancer cells (MCF-7) and human colon cancer cells (SW620). The findings indicated that several compounds exhibited promising antitumor effects. Notably, (E)-1-(4-((4,6-dimorpholino-1,3,5-triazin-2-yl)oxy)phenyl)-3-(thiophen-2-yl)prop-2-en-1-one (3bg) demonstrated efficacy as a broad-spectrum anticancer agent, exhibiting significant activity against the A549, HeLa, and MCF-7 cell lines. Furthermore, (E)-1-(4-((4,6-dimorpholino-1,3,5-triazin-2-yl)oxy)phenyl)-3-phenylprop-2-en-1-one (3bb) displayed the most potent in vitro antitumor activity against the MCF-7 cell line with an IC_(50) value of 16.4 μmol/L, establishing it as the most active compound in assay.展开更多
Photodynamic therapy(PDT)has been established as one of the most promising novel cancer therapies with fewer side-effects and enhanced efficacy compared to the currently available conventional treatments.However,its a...Photodynamic therapy(PDT)has been established as one of the most promising novel cancer therapies with fewer side-effects and enhanced efficacy compared to the currently available conventional treatments.However,its application has been hindered by the limitations that photosensitizers(PS)have.The combination of PS with metallic nanoparticles like platinum nanoparticles(PtNPs),can help to overcome these intrinsic drawbacks.In this work,the combination of PtNPs and the natural photosensitizer riboflavin(RF)is proposed.PtNPs are synthesized using RF(Pt@RF)as reducing and stabilizing agent in a one-step method,obtaining nanoparticles with mesoporous structure for UV triggered PDT.In view of possible future UV irradiation treatments,the degradation products of RF,ribitol(RB)and lumichrome(LC),this last being a photosensitizing byproduct,are also employed for the synthesis of porous PtNPs,obtaining Pt@LC and Pt@RB.When administered in vitro to lung cancer cells,all the samples elicit a strong decrease of cell viability and a decrease of intracellular ATP levels.The antitumoral effect of both Pt@RF and Pt@LC is triggered by UV-A irradiation.This antitumoral activity is caused by the induction of oxidative stress,shown in our study by the decrease in intracellular glutathione and increased expression of antioxidant enzymes.展开更多
The rapid development of rare earth metal elements in the field of photocatalysis is due to their excellent optical and physicochemical properties.Benefiting from the unique external electronic structure of 4f_15d_16S...The rapid development of rare earth metal elements in the field of photocatalysis is due to their excellent optical and physicochemical properties.Benefiting from the unique external electronic structure of 4f_15d_16S_2,superior electronegativity of the 4f orbitals,and strong oxygen storage-release ability in Ce^(4+)/Ce^(3+)reversible pairs,cerium dioxide(CeO_(2))has attracted increasing interest from scientists.Nevertheless,the fast recombination of photoinduced electron-hole pairs and wide energy band gap of bare CeO_(2)significantly limit its practical applications.To overcome the above drawbacks,the construction of heterojunctions has been developed to broaden the absorption spectrum and accelerate the charge transfer.This review presents a mini-review of the synthesis of CeO_(2)-based heterojunctions including typeⅡ,Z-scheme,and S-scheme photocatalysts,as well as the corresponding applications in photocatalytic bactericidal and antitumor therapy.Finally,the latest advancements and potential perspectives on their future development are also discussed.展开更多
Asperfilasin A(1),featuring a unique 5/5 cyclopenta[c]pyrrol-one bicyclic core,represents a newly discovered skeletal cytochalasan isolated from Aspergillus flavipes.The enantioselective total synthesis was efficientl...Asperfilasin A(1),featuring a unique 5/5 cyclopenta[c]pyrrol-one bicyclic core,represents a newly discovered skeletal cytochalasan isolated from Aspergillus flavipes.The enantioselective total synthesis was efficiently accomplished from the key intermediate(S)-6 with three contiguous stereocenters in 5 steps and the synthetic 1 induced G2/M-phase cell cycle arrest of HT29 cells and apoptosis of HL60 and NB4 cells by activation of caspase-3 and degradation of PARP.(S)-6,bearing three contiguous chiral centers,was efficiently constructed by a novel Nazarov cyclization reaction containing basic nitrogen,which was less developed,primarily due to the incompatibility of basic nitrogen under acidic reaction conditions.This reaction allows a wide range of pentadienone substrates containing basic nitrogen to undergo Nazarov cyclization in a single regioselective and diastereoselective manner and is capable of generating three stereocenters simultaneously.Furthermore,the mechanism of the Nazarov cyclization and the origin of the regio-and diastereoselectivity were elucidated by DFT calculations and deuteration experiments,providing valuable insights into the reaction and serving as a guide for future applications involving substrates containing basic nitrogen.展开更多
Objectives:Triphenylphosphine(TPP)and Doxorubicin(DOX)were conjugated to obtain Triphenylphosphine-Doxorubicin(TPP-DOX),which was applied in tumor cells for enhancement of DOX in mitochondria targeting.The study focus...Objectives:Triphenylphosphine(TPP)and Doxorubicin(DOX)were conjugated to obtain Triphenylphosphine-Doxorubicin(TPP-DOX),which was applied in tumor cells for enhancement of DOX in mitochondria targeting.The study focused on investigating the anti-tumor effect of TPP-DOX in combination with radiotherapy throughout in vitro and in vivo studies.Methods:TPP-DOX was synthesized using the carbodiimide method.In vitro experiments were conducted with 4T1 cells(mouse breast cancer cell line)to assess apoptosis induction,mitochondrial targeting,reactive oxygen species(ROS)production,and mitochondrial membrane potential.The research evaluates the effects of TPP-DOX,DOX,and their combinations with radiotherapy.A nude mouse tumor heterograft model was established to investigate the synergistic effect of TPP-DOX and radiotherapy.Results:TPP-DOX was successfully synthesized and scrupulously verified.In vitro experiments showed that compared to DOX,TPP-DOX exhibited enhanced tumor cytotoxicity,improved cellular uptake in 4T1 cells,and increased apoptosis induction.Combined with radiotherapy,TPP-DOX promoted mitochondrial ROS production,reduced mitochondrial membrane potential,and amplified its anti-tumor effect.In vivo experiment confirmed that TPP-DOX combined with radiotherapy exhibited superior anti-tumor activity,promoted tumor tissue apoptosis,inhibited tumor angiogenesis,and showed a favorable in vivo safety profile.Conclusion:The study confirmed that when combined with radiotherapy,TPP-DOX promoted tumor cell apoptosis,and effectively enhanced the anti-tumor effect.In sensitive cells,TPP-DOX demonstrates comparable efficacy to DOX when combined with radiotherapy.TPP-DOX holds significant potential for a broader spectrum of applications and emerges as a valuable candidate for clinical application.These findings provide a promising and efficient therapeutic strategy for tumor treatment with improved efficacy and safety.展开更多
Selenium(Se),an essential micronutrient among the 15 vital elements required for human physiology,exerts its biological functions primarily through its incorporation into selenoproteins.To date,approximately 25 seleno...Selenium(Se),an essential micronutrient among the 15 vital elements required for human physiology,exerts its biological functions primarily through its incorporation into selenoproteins.To date,approximately 25 selenoproteins have been characterized in mammalian systems,including glutathione peroxidase(GPX),thioredoxin reductase(TrxR),and iodothyronine deiodinases(DIOs),all of which exhibit indispensable physiological functions.展开更多
Objectives:Currently,there exist two approaches to the treatment of malignant neoplasms:the Karanahan technology and in situ vaccination,which are based on chronometric delivery of therapeutic agents to the tumor depe...Objectives:Currently,there exist two approaches to the treatment of malignant neoplasms:the Karanahan technology and in situ vaccination,which are based on chronometric delivery of therapeutic agents to the tumor depending on the characteristics of tumor cells,as well as the immune status.The main purpose of this study was to experimentally prove the feasibility of combining the Karanahan technology and in situ vaccination withαOX40 antibodies into a single therapeutic platform to achieve a potent additive antitumor therapeutic effect.Methods:BALB/c mice grafted with B-cellular lymphoma A20 were treated using the Karanahan technology consisting of intraperitoneal cyclophosphamide administrations and intratumoral DNA injections according to an individually determined therapeutic regimen,together with in situ vaccination withαOX40.A pathomorphological analysis of the organs of experimental animals that died during the initial attempt to combine the two technologies was carried out.An analysis of blood cell populations was performed to determine the safe time for antibody administration:the number of immune cells capable of activating systemic inflammation(CD11b+Ly-6C+,CD11b+Ly-6G+,CD3–NKp46+CD11b+),the presence of Fc receptor and OX40 on the surface of these cells,and the number of neutrophils activated to NETosis were analyzed.Based on the analysis results,the antitumor efficacy of various modes of combining the Karanahan technology and in situ vaccination was studied.Results:WhenαOX40 was administered 5 h after each treatment using the Karanahan technology,mass death of mice caused by systemic inflammation and multiple organ failure was observed.The state of blood cells after the treatment using the Karanahan technology at the time points corresponding to antibody injections was analyzed to elucidate the reasons for this effect.It was found that at some time points,there occurs activation of the immune system and a powerful release(up to 16%)of monocytes and granulocytes carrying Fc receptor and OX40 on their surface into blood;when interacting withαOX40,they can activate the lytic potential of these cells.Activation of neutrophils to NETosis was also observed.Based on these findings,a study was carried out in different time regimes to combine the Karanahan technology andαOX40 injections.WhenαOX40 was injected into the points of minimal release of myeloid cells into the blood,increased survival rate and the greatest antitumor efficacy were observed:37%of animals survived without relapses on day 100 after experiment initiation.Conclusions:The results obtained indicate that it is possible to combine the Karanahan technology and in situ vaccination withαOX40,with obligatory constant monitoring of the number of myeloid cells in peripheral blood to determine the safe time for antibody injection.展开更多
Zinc(Zn)alloys exhibit substantial potential for application in the domain of metal materials that are both biodegradable and implantable because of their appropriate degradation rate and biocompatibility.Selenium(Se)...Zinc(Zn)alloys exhibit substantial potential for application in the domain of metal materials that are both biodegradable and implantable because of their appropriate degradation rate and biocompatibility.Selenium(Se)has been widely employed in tumor treatment,positioning ZnSe alloys as promising candidates for the development of the next generation of antitumor degradable materials.However,the considerable disparity in melting points and the volatility of elemental Zn and Se pose significant challenges for alloying using conventional melting methods.Here,we report a Zn-4Ag-2Se alloy using silver selenide(Ag2Se)as the Se source for biodegradable implant materials.The alloy's antibacterial and antitumor capabilities,along with its mechanical,corrosion,and biocompatibility properties,were assessed and then compared to the properties of a Zn-4Ag alloy.Both alloys consisted primarily ofη-Zn andε-AgZn3phases,with the Zn-4Ag-2Se alloy additionally containing a minor amount of a ZnSe phase.The hot-rolled(HR)Zn-4Ag-2Se alloy exhibited an ultimate tensile strength of 211.5±2.3 MPa and elongation of 24.9%±0.6%.Additionally,the HR Zn-4Ag-2Se alloy demonstrated an electrochemical corrosion rate of 105.51±1.21μm year^(-1)and degradation rate of 59.8±0.2μm year^(-1)in Hanks'solution,meeting the performance criteria for degradable implant materials.The HR Zn-4Ag-2Se alloy also exhibited excellent antibacterial activity,evidenced by an inhibition zone diameter(IZD)of 2.22±0.01 mm and colony-forming unit count of 58±2.The HR Zn-4Ag-2Se alloy did not inhibit the proliferation of MC3T3-E1 cells but promoted reactive oxygen species production and finally cell death toward MG63 osteosarcoma cells.展开更多
背景:沸石基咪唑盐框架8及其衍生物凭借优异的药物控释能力在组织工程领域展现出广泛的应用潜力。目的:综述沸石基咪唑盐框架8及其改性材料在活性氧生成与清除中的作用机制,探讨它们在抗肿瘤、抗菌及组织保护领域的应用潜力,分析未来发...背景:沸石基咪唑盐框架8及其衍生物凭借优异的药物控释能力在组织工程领域展现出广泛的应用潜力。目的:综述沸石基咪唑盐框架8及其改性材料在活性氧生成与清除中的作用机制,探讨它们在抗肿瘤、抗菌及组织保护领域的应用潜力,分析未来发展方向与挑战。方法:由第一作者通过中国知网、PubMed等数据库检索2000-2024年相关文献,中文检索关键词为“沸石基咪唑盐框架8,活性氧,抗菌,抗肿瘤,活性氧吸收,活性氧平衡,组织修复”,英文检索关键词为“ZIF-8,ROS,antibacterial,antitumor,ROS absorption,Balance of ROS,Tissue regeneration”,最终筛选69篇高质量文献进行综述分析。结果与结论:通过调控沸石基咪唑盐框架8及其改性材料的带隙结构、优化电子转移效率可显著提升光生载流子的分离与迁移效率,从而增强催化反应性能,提高活性氧的产生效率,实现更高效、更具靶向性的抗肿瘤及抗菌作用;同时,采用抗氧化酶系统或表面改性技术构建的活性氧清除装置,能够精准平衡多余活性氧,实现对细胞的有效保护。这种基于带隙调控与电子转移优化的双向调控机制,为动态管理活性氧生成与清除提供了重要策略,在抗肿瘤、抗菌及组织保护等领域展现出广阔的应用前景。展开更多
Lipid nanoparticles have become attractive for its prominent properties recent years. In this paper, in vivo anti-tumor efficacy of nanostructured lipid carrier of dihydroartemisinin （DHA-NLC） were evaluated in sarc...Lipid nanoparticles have become attractive for its prominent properties recent years. In this paper, in vivo anti-tumor efficacy of nanostructured lipid carrier of dihydroartemisinin （DHA-NLC） were evaluated in sarcoma 180-bearing mice model through intraperitoneal （i.p.） administration. In vivo biodistribution was also investigated in Kunming mice bearing S180. Results demonstrated that the intraperitoneally injected DHA-NLC could significantly inhibit tumor growth at the dose levels of 20, 40 and 80 mg/kg, and their inhibition rates were 71.24%, 79.20% and 85.74%, respectively. The biodistribution of DHA after intraperitoneal injection of DHA-NLC in S180-bearing mice is remarkably different from the DHA solution. Therefore, DHA encapsulated in NLC does demonstrate superior anticancer effect to DHA suspension on S 180-bearing mice at the same dose and displayed a dose-dependent antitumor efficacy.展开更多
Several cancer cell lines(epithelioma cells or leukemia cells)from human being or mouse were first used to study the antitumor activity of the Ganoderma lucidum spore alcohol extract(GLSAE)in vitro by the MTT test A ...Several cancer cell lines(epithelioma cells or leukemia cells)from human being or mouse were first used to study the antitumor activity of the Ganoderma lucidum spore alcohol extract(GLSAE)in vitro by the MTT test A comparision was made between the sporodermbroken(SB)and sporoderm nonbroken(SN)GLSAE It was showed that both GLSAE SB and GLSAE SN could inhibit the proliferation of these cancer cells,but the activity of GLSAE SB was much higher than that of GLSAE SN These results suggested that Ganoderma lucidum spore could probably be used for tumor treatment展开更多
目的:综合评价安徽医科大学附属亳州医院抗肿瘤药物临床合理应用管理指标,为后续抗肿瘤药物管理提供参考。方法:以季度为节点,提取该院2022−2024年(2022Q1表示2022年第一季度,以此类推)抗肿瘤药物的14项管理指标,包括门诊、住院患者限...目的:综合评价安徽医科大学附属亳州医院抗肿瘤药物临床合理应用管理指标,为后续抗肿瘤药物管理提供参考。方法:以季度为节点,提取该院2022−2024年(2022Q1表示2022年第一季度,以此类推)抗肿瘤药物的14项管理指标,包括门诊、住院患者限制使用级抗肿瘤药物使用率等。结合指标难度赋权法、加权逼近理想解排序(technique for order preference by similarity to ideal solution,Topsis)法和秩和比(Rank-sum ratio,RSR)法,对12个季度的管理指标进行评价并分档。结果:2022Q2、Q4和2023Q4的管理指标均处于“上”级别(C_(i)≥0.6435),2024Q1−Q4及其他4个季度的管理指标维持在“中”级别(0.3751≤Ci≤0.6244),处于“差”级别的季度仅有2022Q1(C_(i)=0.1506)。结论:基于指标难度赋权-Topsis-RSR法建立的抗肿瘤药物管理指标评价方法,赋权合理、评价结果具体,对后续工作具有一定的指导意义。展开更多
The purpose of this study was to investigate the potential antitumor efficacy of conjugated linoleic acid-paclitaxel （CLA-PTX） on B16-F10 melanoma cell line in vitro and in vivo. The in vitro cytotoxicity, apoptosis...The purpose of this study was to investigate the potential antitumor efficacy of conjugated linoleic acid-paclitaxel （CLA-PTX） on B16-F10 melanoma cell line in vitro and in vivo. The in vitro cytotoxicity, apoptosis and cell cycle of CLA-PTX were investigated. The in vitro cellular uptake of CLA-PTX in B16-F10 cells was also analyzed. The antitumor activity of CLA-PTX was also evaluated in B16-F10 tumor-bearing C57BL6/N mice in vivo. The in vitro cytotoxicity results showed that the IC50 of the CLA-PTX is （4.25±0.43） μM, compared with that of （6.70±0.80） μM in PTX treatment group （P〈0.01）. CLA-PTX increased the percentage of total apoptotic cells compared with that of control and PTX treatment groups （P〈0.01）. Compared with untreated cells, CLA-PTX arrested cell cycle progression at the S phase, whereas PTX caused accumulation of cell at GE-M phase both along with the reduction of the cellular fraction arrested at the G1 phase. The amount of cellular uptake of CLA-PTX was significantly higher than that of PTX （P〈0.01）. The in vivo antitumor activity of CLA-PTX was significantly higher than that of control and PTX treatment groups （P〈0.01 or P〈0.05）. In conclusion, our study demonstrated that CLA-PTX has significant antitumor activity in B 16-F 10 cell line.展开更多
基金the National Natural Science Foundation of China (Nos.21907076 and 31901908)the Natural Science Foundation of Tianjin (No.22JCQNJC01570)。
文摘Poor solubility often results in low efficacy of antitumor drugs.Nevertheless,limited research has been conducted on the potential decrease in drug efficacy following the self-assembly of hydrophobic pure drugs into nanodrugs,and solutions to this problem are even rarer.Loading water-insoluble antitumor drugs into nanocarriers offers a promising solution.However,intricate carrier preparation,limited drug loading capacity,and carrier-associated safety remain key challenges.In this study,based on the discovery that hydrophobic gambogic acid(GA) self-assembles into nanostructures with diminished antitumor efficacy in aqueous environments,we developed a carrier-free nanodrug system,designated as GA-S-S-AS nanoparticles(NPs),characterized by straightforward preparation,high drug loading,fluorescence imaging,tumor-targeting,and responsive drug release in reducing environments.Specifically,the hydrophobic GA was covalently linked to the hydrophilic aptamer through a disulfide bond and then self-assembled into the nanodrugs.About 92 % of drug was encapsulated in self-assembled NPs,demonstrating remarkable stability under physiological conditions and controlled release of GA in the high-glutathione environment characteristic of tumor sites.Furthermore,by utilizing the synergistic interaction between the enhanced permeability and retention(EPR) effect and ligand-receptor active targeting mechanisms,the nanodrugs significantly increased the accumulation of GA at tumor locations.Consequently,the nanodrugs exhibited optimal therapeutic efficacy against the tumor both in vitro and in vivo,significantly inhibiting tumor growth.Furthermore,the nanodrugs demonstrated enhanced biosafety compared to free GA,effectively reducing GA-induced hepatotoxicity.Taken together,these findings underscore the significant potential of this multifunctional carrier-free nanodrugs for the targeted delivery of GA,thereby laying a foundation for future endeavors aimed at developing novel formulations of hydrophobic antitumor drugs.
文摘Employing the principle of active moiety concatenation, a novel series of symmetrical triazine compounds were designed. A series of novel triazine compounds were synthesized using cyanuric chloride, amines, and chalcones as the initial reactants. The structures of these compounds were characterized through FT-IR, 1H-NMR, 13C-NMR, high-resolution mass spectrometry (HRMS) and high performance liquid chromatography (HPLC). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetra- zolium bromide (MTT) assay was employed to evaluate the in vitro anti-proliferative activity of the new s-triazine compounds against human lung cancer cells (A549), human cervical cancer cells (HeLa), human breast cancer cells (MCF-7) and human colon cancer cells (SW620). The findings indicated that several compounds exhibited promising antitumor effects. Notably, (E)-1-(4-((4,6-dimorpholino-1,3,5-triazin-2-yl)oxy)phenyl)-3-(thiophen-2-yl)prop-2-en-1-one (3bg) demonstrated efficacy as a broad-spectrum anticancer agent, exhibiting significant activity against the A549, HeLa, and MCF-7 cell lines. Furthermore, (E)-1-(4-((4,6-dimorpholino-1,3,5-triazin-2-yl)oxy)phenyl)-3-phenylprop-2-en-1-one (3bb) displayed the most potent in vitro antitumor activity against the MCF-7 cell line with an IC_(50) value of 16.4 μmol/L, establishing it as the most active compound in assay.
基金funded by the Horizon Europe Project"PERSEUS"(No.101099423)financed by the Ministry of Universities under application 33.50.460A.752by the European Union NextGenerationEU/PRTR through a contract Margarita Salas from Universidade de Vigo.
文摘Photodynamic therapy(PDT)has been established as one of the most promising novel cancer therapies with fewer side-effects and enhanced efficacy compared to the currently available conventional treatments.However,its application has been hindered by the limitations that photosensitizers(PS)have.The combination of PS with metallic nanoparticles like platinum nanoparticles(PtNPs),can help to overcome these intrinsic drawbacks.In this work,the combination of PtNPs and the natural photosensitizer riboflavin(RF)is proposed.PtNPs are synthesized using RF(Pt@RF)as reducing and stabilizing agent in a one-step method,obtaining nanoparticles with mesoporous structure for UV triggered PDT.In view of possible future UV irradiation treatments,the degradation products of RF,ribitol(RB)and lumichrome(LC),this last being a photosensitizing byproduct,are also employed for the synthesis of porous PtNPs,obtaining Pt@LC and Pt@RB.When administered in vitro to lung cancer cells,all the samples elicit a strong decrease of cell viability and a decrease of intracellular ATP levels.The antitumoral effect of both Pt@RF and Pt@LC is triggered by UV-A irradiation.This antitumoral activity is caused by the induction of oxidative stress,shown in our study by the decrease in intracellular glutathione and increased expression of antioxidant enzymes.
基金Project supported by the National Key Research and Development Program of China(2022YFB3504100,2021YFB3500600)Chunhui Project Foundation of the Education Department of China(202200554)。
文摘The rapid development of rare earth metal elements in the field of photocatalysis is due to their excellent optical and physicochemical properties.Benefiting from the unique external electronic structure of 4f_15d_16S_2,superior electronegativity of the 4f orbitals,and strong oxygen storage-release ability in Ce^(4+)/Ce^(3+)reversible pairs,cerium dioxide(CeO_(2))has attracted increasing interest from scientists.Nevertheless,the fast recombination of photoinduced electron-hole pairs and wide energy band gap of bare CeO_(2)significantly limit its practical applications.To overcome the above drawbacks,the construction of heterojunctions has been developed to broaden the absorption spectrum and accelerate the charge transfer.This review presents a mini-review of the synthesis of CeO_(2)-based heterojunctions including typeⅡ,Z-scheme,and S-scheme photocatalysts,as well as the corresponding applications in photocatalytic bactericidal and antitumor therapy.Finally,the latest advancements and potential perspectives on their future development are also discussed.
基金supported by the National Natural Science Foundation of China(Nos.81725021,81903461)the National Key R&D Program of China(No.2022YFA1503200)the Natural Science Foundation of Hubei Province(No.ZRMS2023000340)。
文摘Asperfilasin A(1),featuring a unique 5/5 cyclopenta[c]pyrrol-one bicyclic core,represents a newly discovered skeletal cytochalasan isolated from Aspergillus flavipes.The enantioselective total synthesis was efficiently accomplished from the key intermediate(S)-6 with three contiguous stereocenters in 5 steps and the synthetic 1 induced G2/M-phase cell cycle arrest of HT29 cells and apoptosis of HL60 and NB4 cells by activation of caspase-3 and degradation of PARP.(S)-6,bearing three contiguous chiral centers,was efficiently constructed by a novel Nazarov cyclization reaction containing basic nitrogen,which was less developed,primarily due to the incompatibility of basic nitrogen under acidic reaction conditions.This reaction allows a wide range of pentadienone substrates containing basic nitrogen to undergo Nazarov cyclization in a single regioselective and diastereoselective manner and is capable of generating three stereocenters simultaneously.Furthermore,the mechanism of the Nazarov cyclization and the origin of the regio-and diastereoselectivity were elucidated by DFT calculations and deuteration experiments,providing valuable insights into the reaction and serving as a guide for future applications involving substrates containing basic nitrogen.
基金supported by the Zhejiang Provincial Natural Science Foundation of China(LY24H300001)the Medical and Health Research Project of Zhejiang Province(KY202302130009)National Health Service Research Project(WKZX2024CX501205).
文摘Objectives:Triphenylphosphine(TPP)and Doxorubicin(DOX)were conjugated to obtain Triphenylphosphine-Doxorubicin(TPP-DOX),which was applied in tumor cells for enhancement of DOX in mitochondria targeting.The study focused on investigating the anti-tumor effect of TPP-DOX in combination with radiotherapy throughout in vitro and in vivo studies.Methods:TPP-DOX was synthesized using the carbodiimide method.In vitro experiments were conducted with 4T1 cells(mouse breast cancer cell line)to assess apoptosis induction,mitochondrial targeting,reactive oxygen species(ROS)production,and mitochondrial membrane potential.The research evaluates the effects of TPP-DOX,DOX,and their combinations with radiotherapy.A nude mouse tumor heterograft model was established to investigate the synergistic effect of TPP-DOX and radiotherapy.Results:TPP-DOX was successfully synthesized and scrupulously verified.In vitro experiments showed that compared to DOX,TPP-DOX exhibited enhanced tumor cytotoxicity,improved cellular uptake in 4T1 cells,and increased apoptosis induction.Combined with radiotherapy,TPP-DOX promoted mitochondrial ROS production,reduced mitochondrial membrane potential,and amplified its anti-tumor effect.In vivo experiment confirmed that TPP-DOX combined with radiotherapy exhibited superior anti-tumor activity,promoted tumor tissue apoptosis,inhibited tumor angiogenesis,and showed a favorable in vivo safety profile.Conclusion:The study confirmed that when combined with radiotherapy,TPP-DOX promoted tumor cell apoptosis,and effectively enhanced the anti-tumor effect.In sensitive cells,TPP-DOX demonstrates comparable efficacy to DOX when combined with radiotherapy.TPP-DOX holds significant potential for a broader spectrum of applications and emerges as a valuable candidate for clinical application.These findings provide a promising and efficient therapeutic strategy for tumor treatment with improved efficacy and safety.
基金Financial support from the Science and Technology Innovation Program of Hunan Province(No.2022RC4044)。
文摘Selenium(Se),an essential micronutrient among the 15 vital elements required for human physiology,exerts its biological functions primarily through its incorporation into selenoproteins.To date,approximately 25 selenoproteins have been characterized in mammalian systems,including glutathione peroxidase(GPX),thioredoxin reductase(TrxR),and iodothyronine deiodinases(DIOs),all of which exhibit indispensable physiological functions.
基金supported by Inga N.Zaitseva“Karanahan”LLC and the Ministry of Science and Higher Education of the Russian Federation via the Institute of Cytology and Genetics(State Budget Project No.FWNR-2022-0016).
文摘Objectives:Currently,there exist two approaches to the treatment of malignant neoplasms:the Karanahan technology and in situ vaccination,which are based on chronometric delivery of therapeutic agents to the tumor depending on the characteristics of tumor cells,as well as the immune status.The main purpose of this study was to experimentally prove the feasibility of combining the Karanahan technology and in situ vaccination withαOX40 antibodies into a single therapeutic platform to achieve a potent additive antitumor therapeutic effect.Methods:BALB/c mice grafted with B-cellular lymphoma A20 were treated using the Karanahan technology consisting of intraperitoneal cyclophosphamide administrations and intratumoral DNA injections according to an individually determined therapeutic regimen,together with in situ vaccination withαOX40.A pathomorphological analysis of the organs of experimental animals that died during the initial attempt to combine the two technologies was carried out.An analysis of blood cell populations was performed to determine the safe time for antibody administration:the number of immune cells capable of activating systemic inflammation(CD11b+Ly-6C+,CD11b+Ly-6G+,CD3–NKp46+CD11b+),the presence of Fc receptor and OX40 on the surface of these cells,and the number of neutrophils activated to NETosis were analyzed.Based on the analysis results,the antitumor efficacy of various modes of combining the Karanahan technology and in situ vaccination was studied.Results:WhenαOX40 was administered 5 h after each treatment using the Karanahan technology,mass death of mice caused by systemic inflammation and multiple organ failure was observed.The state of blood cells after the treatment using the Karanahan technology at the time points corresponding to antibody injections was analyzed to elucidate the reasons for this effect.It was found that at some time points,there occurs activation of the immune system and a powerful release(up to 16%)of monocytes and granulocytes carrying Fc receptor and OX40 on their surface into blood;when interacting withαOX40,they can activate the lytic potential of these cells.Activation of neutrophils to NETosis was also observed.Based on these findings,a study was carried out in different time regimes to combine the Karanahan technology andαOX40 injections.WhenαOX40 was injected into the points of minimal release of myeloid cells into the blood,increased survival rate and the greatest antitumor efficacy were observed:37%of animals survived without relapses on day 100 after experiment initiation.Conclusions:The results obtained indicate that it is possible to combine the Karanahan technology and in situ vaccination withαOX40,with obligatory constant monitoring of the number of myeloid cells in peripheral blood to determine the safe time for antibody injection.
基金financially supported by the National Natural Science Foundation of China(Nos.52401064 and 12472101)the Scientific Research Fund of Hunan Provincial Education Department(No.24B0172)+1 种基金Australian Research Council(ARC)through the discovery grants(No.DP240101131)the Post-graduate Scientific Research Innovation Project of Hunan Province(No.CX20230657)
文摘Zinc(Zn)alloys exhibit substantial potential for application in the domain of metal materials that are both biodegradable and implantable because of their appropriate degradation rate and biocompatibility.Selenium(Se)has been widely employed in tumor treatment,positioning ZnSe alloys as promising candidates for the development of the next generation of antitumor degradable materials.However,the considerable disparity in melting points and the volatility of elemental Zn and Se pose significant challenges for alloying using conventional melting methods.Here,we report a Zn-4Ag-2Se alloy using silver selenide(Ag2Se)as the Se source for biodegradable implant materials.The alloy's antibacterial and antitumor capabilities,along with its mechanical,corrosion,and biocompatibility properties,were assessed and then compared to the properties of a Zn-4Ag alloy.Both alloys consisted primarily ofη-Zn andε-AgZn3phases,with the Zn-4Ag-2Se alloy additionally containing a minor amount of a ZnSe phase.The hot-rolled(HR)Zn-4Ag-2Se alloy exhibited an ultimate tensile strength of 211.5±2.3 MPa and elongation of 24.9%±0.6%.Additionally,the HR Zn-4Ag-2Se alloy demonstrated an electrochemical corrosion rate of 105.51±1.21μm year^(-1)and degradation rate of 59.8±0.2μm year^(-1)in Hanks'solution,meeting the performance criteria for degradable implant materials.The HR Zn-4Ag-2Se alloy also exhibited excellent antibacterial activity,evidenced by an inhibition zone diameter(IZD)of 2.22±0.01 mm and colony-forming unit count of 58±2.The HR Zn-4Ag-2Se alloy did not inhibit the proliferation of MC3T3-E1 cells but promoted reactive oxygen species production and finally cell death toward MG63 osteosarcoma cells.
文摘背景:沸石基咪唑盐框架8及其衍生物凭借优异的药物控释能力在组织工程领域展现出广泛的应用潜力。目的:综述沸石基咪唑盐框架8及其改性材料在活性氧生成与清除中的作用机制,探讨它们在抗肿瘤、抗菌及组织保护领域的应用潜力,分析未来发展方向与挑战。方法:由第一作者通过中国知网、PubMed等数据库检索2000-2024年相关文献,中文检索关键词为“沸石基咪唑盐框架8,活性氧,抗菌,抗肿瘤,活性氧吸收,活性氧平衡,组织修复”,英文检索关键词为“ZIF-8,ROS,antibacterial,antitumor,ROS absorption,Balance of ROS,Tissue regeneration”,最终筛选69篇高质量文献进行综述分析。结果与结论:通过调控沸石基咪唑盐框架8及其改性材料的带隙结构、优化电子转移效率可显著提升光生载流子的分离与迁移效率,从而增强催化反应性能,提高活性氧的产生效率,实现更高效、更具靶向性的抗肿瘤及抗菌作用;同时,采用抗氧化酶系统或表面改性技术构建的活性氧清除装置,能够精准平衡多余活性氧,实现对细胞的有效保护。这种基于带隙调控与电子转移优化的双向调控机制,为动态管理活性氧生成与清除提供了重要策略,在抗肿瘤、抗菌及组织保护等领域展现出广阔的应用前景。
基金Fundamental Research Funds of Lanzhou University for the Central Universities (Grant No. lzujbky-2012-85)the Lanzhou Science and Technology Bureau (Grant No. 2012-2-80)
文摘Lipid nanoparticles have become attractive for its prominent properties recent years. In this paper, in vivo anti-tumor efficacy of nanostructured lipid carrier of dihydroartemisinin （DHA-NLC） were evaluated in sarcoma 180-bearing mice model through intraperitoneal （i.p.） administration. In vivo biodistribution was also investigated in Kunming mice bearing S180. Results demonstrated that the intraperitoneally injected DHA-NLC could significantly inhibit tumor growth at the dose levels of 20, 40 and 80 mg/kg, and their inhibition rates were 71.24%, 79.20% and 85.74%, respectively. The biodistribution of DHA after intraperitoneal injection of DHA-NLC in S180-bearing mice is remarkably different from the DHA solution. Therefore, DHA encapsulated in NLC does demonstrate superior anticancer effect to DHA suspension on S 180-bearing mice at the same dose and displayed a dose-dependent antitumor efficacy.
文摘Several cancer cell lines(epithelioma cells or leukemia cells)from human being or mouse were first used to study the antitumor activity of the Ganoderma lucidum spore alcohol extract(GLSAE)in vitro by the MTT test A comparision was made between the sporodermbroken(SB)and sporoderm nonbroken(SN)GLSAE It was showed that both GLSAE SB and GLSAE SN could inhibit the proliferation of these cancer cells,but the activity of GLSAE SB was much higher than that of GLSAE SN These results suggested that Ganoderma lucidum spore could probably be used for tumor treatment
文摘目的:综合评价安徽医科大学附属亳州医院抗肿瘤药物临床合理应用管理指标,为后续抗肿瘤药物管理提供参考。方法:以季度为节点,提取该院2022−2024年(2022Q1表示2022年第一季度,以此类推)抗肿瘤药物的14项管理指标,包括门诊、住院患者限制使用级抗肿瘤药物使用率等。结合指标难度赋权法、加权逼近理想解排序(technique for order preference by similarity to ideal solution,Topsis)法和秩和比(Rank-sum ratio,RSR)法,对12个季度的管理指标进行评价并分档。结果:2022Q2、Q4和2023Q4的管理指标均处于“上”级别(C_(i)≥0.6435),2024Q1−Q4及其他4个季度的管理指标维持在“中”级别(0.3751≤Ci≤0.6244),处于“差”级别的季度仅有2022Q1(C_(i)=0.1506)。结论:基于指标难度赋权-Topsis-RSR法建立的抗肿瘤药物管理指标评价方法,赋权合理、评价结果具体,对后续工作具有一定的指导意义。
基金National Natural Science Foundation of China(Grant No.81172992)the National Basic Research Program of China(973 Program,Grant No.2009CB930300)Innovation Team of Ministry of Education(Grant No.BMU20110263)
文摘The purpose of this study was to investigate the potential antitumor efficacy of conjugated linoleic acid-paclitaxel （CLA-PTX） on B16-F10 melanoma cell line in vitro and in vivo. The in vitro cytotoxicity, apoptosis and cell cycle of CLA-PTX were investigated. The in vitro cellular uptake of CLA-PTX in B16-F10 cells was also analyzed. The antitumor activity of CLA-PTX was also evaluated in B16-F10 tumor-bearing C57BL6/N mice in vivo. The in vitro cytotoxicity results showed that the IC50 of the CLA-PTX is （4.25±0.43） μM, compared with that of （6.70±0.80） μM in PTX treatment group （P〈0.01）. CLA-PTX increased the percentage of total apoptotic cells compared with that of control and PTX treatment groups （P〈0.01）. Compared with untreated cells, CLA-PTX arrested cell cycle progression at the S phase, whereas PTX caused accumulation of cell at GE-M phase both along with the reduction of the cellular fraction arrested at the G1 phase. The amount of cellular uptake of CLA-PTX was significantly higher than that of PTX （P〈0.01）. The in vivo antitumor activity of CLA-PTX was significantly higher than that of control and PTX treatment groups （P〈0.01 or P〈0.05）. In conclusion, our study demonstrated that CLA-PTX has significant antitumor activity in B 16-F 10 cell line.
