A reliable and sensitive strategy which can assess nucleic acid levels in living cells would be essential for fundamental research of biomedical applications. Some nanomaterial-based fluorescence biosensors recently d...A reliable and sensitive strategy which can assess nucleic acid levels in living cells would be essential for fundamental research of biomedical applications. Some nanomaterial-based fluorescence biosensors recently developed for detecting nucleic acids, however, are often with expensive, complicated and timeconsuming preparation process. Here, by using a facile bottom-up synthesis method, a two-dimensional(2 D) coordination polymer(CP) nanosheet, [Cu(tz)](Htz = 1,2,4-triazole), was successfully prepared after optimizing reaction conditions. These ultrathin CP nanosheets with thickness of 4.7 ± 1.1 nm could readily form nanosensors by assembly with DNA probes, which exhibited a low limit of detection(LOD)for p53 DNA fragment as 144 pmol/L. Furthermore, by integrating [Cu(tz)] nanosheets with hybridization chain reaction(HCR) probes, mi R-21, one kind of micro RNA upregulated in many cancer cells, can be sensitively detected with a LOD of 100 pmol/L and monitored in living cells, giving consistent results with those obtained by quantitative reverse-transcription polymerase chain reaction(q RT-PCR) analysis.Thus [Cu(tz)] nanosheets, which not only possess much better nucleic acids sensing performance than bulk cystals, but also exhibit nucleic acid delivery functions, could be used as a novel nanoplatform in biomedical imaging and sensing applications.展开更多
Gastric cancer(GC)ranks fifth in global cancer diagnosis and fourth in cancer-related death.Despite tremendous progress in diagnosis and therapeutic strategies and significant improvements in patient survival,the low ...Gastric cancer(GC)ranks fifth in global cancer diagnosis and fourth in cancer-related death.Despite tremendous progress in diagnosis and therapeutic strategies and significant improvements in patient survival,the low malignancy stage is relatively asymptomatic and many GC cases are diagnosed at advanced stages,which leads to unsatisfactory prognosis and high recurrence rates.With the recent advances in genome analysis,biomarkers have been identified that have clinical importance for GC diagnosis,treatment,and prognosis.Modern molecular classifications have uncovered the vital roles that signaling pathways,including EGFR/HER2,p53,PI3K,immune checkpoint pathways,and cell adhesion signaling molecules,play in GC tumorigenesis,progression,metastasis,and therapeutic responsiveness.These biomarkers and molecular classifications open the way for more precise diagnoses and treatments for GC patients.Nevertheless,the relative significance,temporal activation,interaction with GC risk factors,and crosstalk between these signaling pathways in GC are not well understood.Here,we review the regulatory roles of signaling pathways in GC potential biomarkers,and therapeutic targets with an emphasis on recent discoveries.Current therapies,including signaling-based and immunotherapies exploited in the past decade,and the development of treatment for GC,particularly the challenges in developing precision medications,are discussed.These advances provide a direction for the integration of clinical,molecular,and genomic profiles to improve GC diagnosis and treatments.展开更多
Drug resistance is a major hurdle in cancer treatment and a key cause of poor prognosis.Epitranscriptomics and epiproteomics are crucial in cell proliferation,migration,invasion,and epithelial–mesenchymal transition....Drug resistance is a major hurdle in cancer treatment and a key cause of poor prognosis.Epitranscriptomics and epiproteomics are crucial in cell proliferation,migration,invasion,and epithelial–mesenchymal transition.In recent years,epitranscriptomic and epiproteomic modification has been investigated on their roles in overcoming drug resistance.In this review article,we summarized the recent progress in overcoming cancer drug resistance in three novel aspects:(i)mRNA modification,which includes alternative splicing,A-to-I modification and mRNA methylation;(ii)noncoding RNAs modification,which involves miRNAs,lncRNAs,and circRNAs;and(iii)posttranslational modification on molecules encompasses drug inactivation/efflux,drug target modifications,DNA damage repair,cell death resistance,EMT,and metastasis.In addition,we discussed the therapeutic implications of targeting some classical chemotherapeutic drugs such as cisplatin,5-fluorouridine,and gefitinib via these modifications.Taken together,this review highlights the importance of epitranscriptomic and epiproteomic modification in cancer drug resistance and provides new insights on potential therapeutic targets to reverse cancer drug resistance.展开更多
Synergistic therapy combines multiple therapeutic approaches in one shot,thus could significantly amplify the therapeutic effects.However,how to design the desirable combination to maximize the synergistic effect is s...Synergistic therapy combines multiple therapeutic approaches in one shot,thus could significantly amplify the therapeutic effects.However,how to design the desirable combination to maximize the synergistic effect is still a big challenge in cancer management.Herein,a nanoagent composed of glucose oxidase(GOx)and upconversion nanoparticles(UCNPs)were constructed for programmable starving-photodynamic synergistic cancer therapy through cascade glucose oxidation and hydrogen peroxide photolysis.In this nanoagent,GOx modulated the tumor glucose metabolism and consumed the β-D-glucose to produce H2O2.The glucose depletion induced"starvation"in cancer cells and caused cell death.Afterwards,the generated H2O2 was photolyzed by the invisible ultraviolet emission of UCNPs under near-infrared light excitation at 980 nm.The toxic hydroxyl radicals produced by photolysis further induced cancer cell death.Both in vitro and in vivo experiments confirmed that this starving-photodynamic synergistic therapy significantly outran any single therapy.This study paves an avenue to design programmable starving-photodynamic synergistic therapy for cancer management.展开更多
基金supported by the National Key Research and Development Program of China (No.2018YFA0902801)the National Natural Science Foundations of China (Nos.21775169,21801259 and 21974153)+4 种基金the Scientific Technology Project of Shenzhen City (No.JCYJ20200109142410170)the Scientific Technology Project of Guangzhou City (No.202103000003)the Guangdong Natural Science Foundation (Nos.2018A030313290,2019A1515010587)the Guangdong Science and Technology Plan Project (No.2020B1212060077)the Fundamental Research Funds for the Central Universities,SYSU (No.19lgpy142)。
文摘A reliable and sensitive strategy which can assess nucleic acid levels in living cells would be essential for fundamental research of biomedical applications. Some nanomaterial-based fluorescence biosensors recently developed for detecting nucleic acids, however, are often with expensive, complicated and timeconsuming preparation process. Here, by using a facile bottom-up synthesis method, a two-dimensional(2 D) coordination polymer(CP) nanosheet, [Cu(tz)](Htz = 1,2,4-triazole), was successfully prepared after optimizing reaction conditions. These ultrathin CP nanosheets with thickness of 4.7 ± 1.1 nm could readily form nanosensors by assembly with DNA probes, which exhibited a low limit of detection(LOD)for p53 DNA fragment as 144 pmol/L. Furthermore, by integrating [Cu(tz)] nanosheets with hybridization chain reaction(HCR) probes, mi R-21, one kind of micro RNA upregulated in many cancer cells, can be sensitively detected with a LOD of 100 pmol/L and monitored in living cells, giving consistent results with those obtained by quantitative reverse-transcription polymerase chain reaction(q RT-PCR) analysis.Thus [Cu(tz)] nanosheets, which not only possess much better nucleic acids sensing performance than bulk cystals, but also exhibit nucleic acid delivery functions, could be used as a novel nanoplatform in biomedical imaging and sensing applications.
基金National Natural Science Foundation of China#U20A20379National Key Research and Development Program of China#2018YFA0902801+2 种基金100 Top Talents Program of Sun Yat-Sen University(ZSQYBRJH0001)Guangdong Basic and Applied Basic Research Foundation#2021A1515010117Guangdong Provincial Key Laboratory of Digestive Cancer Research#2021B1212040006.
文摘Gastric cancer(GC)ranks fifth in global cancer diagnosis and fourth in cancer-related death.Despite tremendous progress in diagnosis and therapeutic strategies and significant improvements in patient survival,the low malignancy stage is relatively asymptomatic and many GC cases are diagnosed at advanced stages,which leads to unsatisfactory prognosis and high recurrence rates.With the recent advances in genome analysis,biomarkers have been identified that have clinical importance for GC diagnosis,treatment,and prognosis.Modern molecular classifications have uncovered the vital roles that signaling pathways,including EGFR/HER2,p53,PI3K,immune checkpoint pathways,and cell adhesion signaling molecules,play in GC tumorigenesis,progression,metastasis,and therapeutic responsiveness.These biomarkers and molecular classifications open the way for more precise diagnoses and treatments for GC patients.Nevertheless,the relative significance,temporal activation,interaction with GC risk factors,and crosstalk between these signaling pathways in GC are not well understood.Here,we review the regulatory roles of signaling pathways in GC potential biomarkers,and therapeutic targets with an emphasis on recent discoveries.Current therapies,including signaling-based and immunotherapies exploited in the past decade,and the development of treatment for GC,particularly the challenges in developing precision medications,are discussed.These advances provide a direction for the integration of clinical,molecular,and genomic profiles to improve GC diagnosis and treatments.
基金supported by grants from the Guangdong Basic and Applied Basic Research fund project(2019B1515120033)the Science and Technology Foundation of Shenzhen(JCYJ20180305164128430)+2 种基金the International Cooperation Foundation of Shenzhen(GJHZ20180928171602104)the Shenzhen Economic and Information Committee“Innovation Chain and Industry Chain”integration special support plan project(20180225112449943)the Shenzhen Public Service Platform on Tumor Precision Medicine and Molecular Diagnosis.
文摘Drug resistance is a major hurdle in cancer treatment and a key cause of poor prognosis.Epitranscriptomics and epiproteomics are crucial in cell proliferation,migration,invasion,and epithelial–mesenchymal transition.In recent years,epitranscriptomic and epiproteomic modification has been investigated on their roles in overcoming drug resistance.In this review article,we summarized the recent progress in overcoming cancer drug resistance in three novel aspects:(i)mRNA modification,which includes alternative splicing,A-to-I modification and mRNA methylation;(ii)noncoding RNAs modification,which involves miRNAs,lncRNAs,and circRNAs;and(iii)posttranslational modification on molecules encompasses drug inactivation/efflux,drug target modifications,DNA damage repair,cell death resistance,EMT,and metastasis.In addition,we discussed the therapeutic implications of targeting some classical chemotherapeutic drugs such as cisplatin,5-fluorouridine,and gefitinib via these modifications.Taken together,this review highlights the importance of epitranscriptomic and epiproteomic modification in cancer drug resistance and provides new insights on potential therapeutic targets to reverse cancer drug resistance.
基金financially supported by the National Natural Science Foundation of China (21807073, 31771036 and 51703132)the Basic Research Program of Shenzhen (JCYJ20170818144745087, JCYJ20180507182413022 and JCYJ20170412111100742)+2 种基金Guangdong Province Natural Science Foundation of Major Basic Research and Cultivation Project (2018B030308003)Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions of China (161032)China Postdoctoral Science Foundation (2018M630987 and 2019T120752)
文摘Synergistic therapy combines multiple therapeutic approaches in one shot,thus could significantly amplify the therapeutic effects.However,how to design the desirable combination to maximize the synergistic effect is still a big challenge in cancer management.Herein,a nanoagent composed of glucose oxidase(GOx)and upconversion nanoparticles(UCNPs)were constructed for programmable starving-photodynamic synergistic cancer therapy through cascade glucose oxidation and hydrogen peroxide photolysis.In this nanoagent,GOx modulated the tumor glucose metabolism and consumed the β-D-glucose to produce H2O2.The glucose depletion induced"starvation"in cancer cells and caused cell death.Afterwards,the generated H2O2 was photolyzed by the invisible ultraviolet emission of UCNPs under near-infrared light excitation at 980 nm.The toxic hydroxyl radicals produced by photolysis further induced cancer cell death.Both in vitro and in vivo experiments confirmed that this starving-photodynamic synergistic therapy significantly outran any single therapy.This study paves an avenue to design programmable starving-photodynamic synergistic therapy for cancer management.
