The published article titled“MicroRNA-133b Inhibits Proliferation,Cellular Migration,and Invasion via Targeting LASP1 in Hepatocarcinoma Cells”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1269–1282.
Oncology Research Editorial Office Published:19 January 2026 The published article titled“miR-202 Promotes Cell Apoptosis in Esophageal Squamous Cell Carcinoma by Targeting HSF2”has been retracted from Oncology Rese...Oncology Research Editorial Office Published:19 January 2026 The published article titled“miR-202 Promotes Cell Apoptosis in Esophageal Squamous Cell Carcinoma by Targeting HSF2”has been retracted from Oncology Research,Vol.25,No.2,2017,pp.215-223.DOI:10.3727/096504016X14732772150541 URL:https://www.techscience.com/or/v25n2/56800.展开更多
Oncology Research Editorial Office Published:19 January 2026 The published article titled“miR-126-5p Restoration Promotes Cell Apoptosis in Cervical Cancer by Targeting Bcl2l2”has been retracted from Oncology Resear...Oncology Research Editorial Office Published:19 January 2026 The published article titled“miR-126-5p Restoration Promotes Cell Apoptosis in Cervical Cancer by Targeting Bcl2l2”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.463-470.DOI:10.3727/096504016X14685034103879 URL:https://www.techscience.com/or/v25n4/56826.展开更多
Neutrophil extracellular traps(NETs)have emerged as key mediators of cardiovascular diseases(CVDs),linking innate immune activation to vascular injury,thrombosis,and maladaptive remodeling.This review synthesizes rece...Neutrophil extracellular traps(NETs)have emerged as key mediators of cardiovascular diseases(CVDs),linking innate immune activation to vascular injury,thrombosis,and maladaptive remodeling.This review synthesizes recent insights into the molecular and cellular pathways driving NET formation,including post-translational modifications,metabolic reprogramming,inflammasome signaling,and autophagy.It highlights the role of NETs in atherosclerosis,thrombosis,myocardial ischemia-reperfusion injury,and hypertension,emphasizing common control points such as peptidylarginine deiminase 4(PAD4)-dependent histone citrullination and nicotinamide adenine dinucleotide phosphate oxidases 2(NOX2)-mediated oxidative stress.Mechanistic interpretation of circulating biomarkers,includingmyeloperoxidase(MPO)-DNA complexes,citrullinated histoneH3,and cell-free DNA,provides a translational bridge between NET biology and patient stratification.Therapeutic strategies targeting NETs are examined through three main approaches:inhibition of NET initiation,enhancement of chromatin clearance,and neutralization of toxic extracellular components,with attention to both established and emerging interventions.In contrast to previous reviews,this study highlights the novelty of a mechano-therapeutic framework by providing a mechanistic roadmap linking NET formation pathways to therapeutic targeting in cardiovascular disease.Moving forward,integrating mechanistic information with biomarker discovery,precision profiling,and targeted therapies offers innovative strategies to reduce vascular inflammation and improve outcomes in cardiovascular disease.展开更多
The potential of messenger RNA(m RNA)as a therapeutic tool for treating diseases has garnered considerable interest,especially in the wake of the successful creation of m RNA vaccines to counter corona virus disease 2...The potential of messenger RNA(m RNA)as a therapeutic tool for treating diseases has garnered considerable interest,especially in the wake of the successful creation of m RNA vaccines to counter corona virus disease 2019(COVID-19).Nucleic acid-based drug gene therapies have emerged as exceptionally promising avenues for combating disease.Furthermore,lipid nanoparticles(LNPs)are ideal carriers for nucleic acid delivery owing to their ionic nature,which enables nucleic acids to electrostatically interact with intracellular membranes,thereby promoting efficient intracellular nucleic acid release.Unfortunately,the effectiveness of LNPs in targeting organs beyond the liver is relatively poor.Thus,enhanced extrahepatic targeting is another important property that would lead to improved in vivo delivery by LNPs.This review focuses on the fundamental characteristics and functions of LNPs developed to facilitate cellular uptake and ensure effective intracellular release of m RNAs.Promising applications,possible advantages and potential challenges associated with use of LNPs in organ specific delivery and release of m RNAs are summarized.Furthermore,the need for future research to address limitations of currently developed LNPs for clinical applications of the m RNA technology is emphasized.展开更多
In recent years,proteolysis-targeting chimeras(PROTACs)have gained widespread attention as an emerging therapeutic approach.PROTACs are bifunctional molecules composed of a target protein-binding ligand,an E3 ubiquiti...In recent years,proteolysis-targeting chimeras(PROTACs)have gained widespread attention as an emerging therapeutic approach.PROTACs are bifunctional molecules composed of a target protein-binding ligand,an E3 ubiquitin ligase ligand,and a linker connecting these ligands.By harnessing the cell’s intrinsic ubiquitin-proteasome system(UPS),they promote the ubiquitination of specific target proteins,leading to their degradation and therapeutic effects.PROTACs show exceptional promise in targeting conventional“undruggable”targets compared to traditional small-molecule inhibitors.This review provides an overview of PROTACs,including their molecular mechanism of action,therapeutic benefits,development history,key design aspects,current research and development challenges,and future trends in nextgeneration PROTAC technology.展开更多
Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensiv...Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensively explores how cancer cells rewire BCAA metabolism to enhance proliferation,survival,and therapy resistance.Tumors manipulate BCAA uptake and catabolism via high expression of transporters like L-type amino acid transporter 1(LAT1)and enzymes including branched chain amino acid transaminase 1(BCAT1),branched chain amino acid transaminase 2(BCAT2),branched-chain alpha-keto acid dehydrogenase(BCKDH),and branched chain alpha-keto acid dehydrogenase kinase(BCKDK).These alterations sustain energy production,biosynthesis,redox homeostasis,and oncogenic signaling(especially mammalian target of rapamycin complex 1[mTORC1]).Crucially,tumor-driven BCAA depletion also shapes an immunosuppressive microenvironment,impairing anti-tumor immunity by limiting essential nutrients for T cells and natural killer(NK)cells.Innovative therapeutic strategies targeting BCAA pathways—ranging from selective small-molecule inhibitors(e.g.,LAT1 and BCAT1/2)to dietary modulation—have shown promising preclinical and early clinical efficacy,highlighting their potential to exploit metabolic vulnerabilities in cancer cells while bolstering immune responses.By integrating multi-omics data and precision targeting approaches,this review underscores the translational significance of BCAA metabolic reprogramming,positioning it as a novel frontier in cancer treatment.展开更多
Cancer is the second leading cause of death globally.Its treatment remains a major challenge due to the disease's complexity,heterogeneity,and adaptive nature.Among the array of available treatments,targeted thera...Cancer is the second leading cause of death globally.Its treatment remains a major challenge due to the disease's complexity,heterogeneity,and adaptive nature.Among the array of available treatments,targeted therapy emerges as a paramount approach to address this substantial unmet clinical need,owing to its precise tumor targeting capabilities and potential for mitigating tumor progression risks.Drug conjugates are in high demand for targeted therapy due to their unique ligand specificity and potent cytotoxicity,thereby significantly enhancing therapeutic efficacy and reducing the incidence of adverse effects.Therefore,as a burgeoning field in biomedical research,it is timely to outline the latest advances in drug conjugates-driven cancer treatment.Herein,we aim to present the emerging breakthroughs in this exciting field at the intersection of target ligands,linkers,payloads,and cancer treatments.This review focuses on several drug conjugates-related strategies,including antibody-drug conjugates(ADCs),peptide-drug conjugates(PDCs),small molecule-drug conjugates(SMDCs),aptamer-drug conjugates(ApDCs)and radionuclide-drug conjugates(RDCs).Finally,we discuss the fundamentals behind drug conjugate-based anticancer therapeutics,along with their inherent advantages and associated challenges,as well as recent research advances.展开更多
Hepatic fibrosis is regulated by the synergistic actions of various cells and cytokines,with the activation and proliferation of hepatic stellate cells(HSCs) being considered the central event in this process.To achie...Hepatic fibrosis is regulated by the synergistic actions of various cells and cytokines,with the activation and proliferation of hepatic stellate cells(HSCs) being considered the central event in this process.To achieve specific targeting of activated hepatic stellate cells(a HSCs) and precise treatment of hepatic fibrosis,this study developed a dual-functional drug delivery system(SIL/c RGD-PEG-PPS PMs) with both targeting and responsive release capabilities.It aims to target the αvβ 3 receptor specifically expressed on the surface of a HSCs using the cyclic peptide c(RGDyk),and to exploit the high reactive oxygen species(ROS) level in the cellular microenvironment to achieve concentrated burst release of drugs at the pathological sites of hepatic fibrosis.Based on multiple assessments,SIL/c RGD-PEG-PPS PMs specifically enhanced the targeted delivery of silybin(SIL) to a HSCs,inhibited the proliferation and migration of a HSCs,and exhibited good biosafety.Additionally,it demonstrated excellent anti-fibrotic activity in fibrotic mice.In summary,this study shows great potential in targeted treatment of hepatic fibrosis and provides a multifunctional tool for advancing the research and therapeutic strategies of hepatic fibrosis.展开更多
Peripheral immunity forms the foundation of tumor immunity,while tumor immunity represents a more refined adaptation of peripheral immune responses.The tumor microenvironment(TME),a localized niche surrounding tumor c...Peripheral immunity forms the foundation of tumor immunity,while tumor immunity represents a more refined adaptation of peripheral immune responses.The tumor microenvironment(TME),a localized niche surrounding tumor cells,is inherently immunosuppressive(1,2).Effective tumor therapy necessitates the dismantling of this microenvironment,aiming to eradicate tumors from the host system.展开更多
Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxyge...Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.展开更多
Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ab...Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ability,the arginine-glycine-aspartic(RGD)peptide and the epidermal growth factor receptor interference(EGFRi)peptide were fused with MAP30,which was named ELRL-MAP30.The efficiency of targeted therapy for triple-negative breast cancer(TNBC)MDA-MB-231 cells,which lack the expression of estrogen receptor(ER),Progesterone receptor(PgR)and human epidermal growth factor receptor-2(HER2),is limited.In this study,we focus on exploring the effect and mechanism of ELRL-MAP30 on TNBC MDA-MB-231 cells.First,we discovered that ELRL-MAP30 significantly inhibited the migration and invasion of MDA-MB-231 cells and induced MDA-MB-231 cell apoptosis.Moreover,ELRL-MAP30 treatment resulted in a significant increase in Bax expression and a decrease in Bcl-2 expression.Furthermore,ELRL-MAP30 triggered apoptosis via the Fak/EGFR/Erk and Ilk/Akt signaling pathways.In addition,recombinant ELRL-MAP30 can inhibit chicken embryonic angiogenesis,and also inhibit the tube formation ability of human umbilical vein endothelial cells(HUVECs),indicating its potential therapeutic effects on tumor angiogenesis.Collectively,these results indicate that ELRL-MAP30 has significant tumor-targeting properties in MDA-MB-231 cancer cells and reveals potential therapeutic effects on angiogenesis.These findings indicate the potential role of ELRL-MAP30 in the targeted treatment of the TNBC cell line MDA-MB-231.展开更多
The published article titled“Overexpression of miR-1283 Inhibits Cell Proliferation and Invasion of Glioma Cells by Targeting ATF4”has been retracted from Oncology Research,Vol.27,No.3,2019,pp.325–334.
The published article titled“Swainsonine inhibits invasion and the EMT process in esophageal carcinoma cells by targeting twist1”has been retracted from Oncology Research,Vol.26,No.8,2018,pp.1207–1213.
The published article titled“MicroRNA-133b Inhibits Cell Proliferation and Invasion in Osteosarcoma by Targeting Sirt1”has been retracted from Oncology Research,Vol.25,No.9,2017,pp.1421–1430.
Developing novel anti-infective drugs is essential to combat antimicrobial resistance,address emerging pathogens,and safeguard global health against evolving infectious threats.A recent publication in the esteemed jou...Developing novel anti-infective drugs is essential to combat antimicrobial resistance,address emerging pathogens,and safeguard global health against evolving infectious threats.A recent publication in the esteemed journal Nature by Qisen Deng et al.reported on the comprehensive evaluation of the therapeutic efficacy of mandimycin against multidrug-resistant(MDR)fungal pathogens.The polyene macrolide antifungal antibiotic,mandimycin,was discovered using a phylogeny-guided natural-product discovery platform.Authors utilized various in vivo mouse models such as systemic and soft-tissue infections to assess the antifungal activity of mandimycin.The efficacy was measured by quantifying the fungal burden in major organs and assessing survival rates.In systemic infections,mandimycin demonstrated significant dose-dependent antifungal efficacy,as compared to amphotericin B,particularly in cases where the latter was ineffective against MDR C.auris.Furthermore,mandimycin showed a favorable safety profile,with low toxicity and no observed side effects at effective doses.The study's findings contribute valuable insights into the potential of mandimycin as a novel antifungal agent,offering hope for improved treatment options against challenging fungal infections.The results pave the way for further research and clinical applications in the fight against antifungal resistance.展开更多
Nanobodies have been extensively demonstrated in biomedical imaging and therapy. However, nanobody probes often suffer from rapid renal clearance due to its small size. Herein, we reported a recombinant nanobody with ...Nanobodies have been extensively demonstrated in biomedical imaging and therapy. However, nanobody probes often suffer from rapid renal clearance due to its small size. Herein, we reported a recombinant nanobody with a 200 amino-acid polypeptide chain consisting of Pro, Ala, and Ser (PAS) at the C-terminal, which can be easily expressed in Escherichia coli with a high yield. The PASylated nanobody was functionalized with a fluorescent dye and the cell labeling properties were characterized by flow cytometry and confocal microscopy. In vivo fluorescence imaging indicated that the PASylated nanobody showed comparable blood circulation time, but ∼1.5 times higher tumor targeting ability as compared to the PEGylated nanobody of comparable molecular weight. Our findings demonstrate that nanobody PASylation is a promising approach to produce long-circulating nanobody probes for imaging and therapeutic applications.展开更多
Nanomedicine holds considerable promise for advancing cancer therapy,however,effective delivery of drugs to solid tumors remains a challenge due to rapid systemic clearance and inefficient cellular uptake.Herein,we ha...Nanomedicine holds considerable promise for advancing cancer therapy,however,effective delivery of drugs to solid tumors remains a challenge due to rapid systemic clearance and inefficient cellular uptake.Herein,we have developed a novel charge-reversible nanogel to deliver paclitaxel(PTX)dimers(DPP)with enhanced stability and targeting precision.The nanogels exhibit a dynamic charge-reversal mechanism responsive to the acidic tumor microenvironment(TME),optimizing the cellular uptake of prodrugs.In the high glutathione(GSH)conditions within cancer cells,the disulfide bonds in the DPP are cleaved,resulting in the intracellular release of active PTX and reduced drug toxicity to normal cells.In vivo pharmacokinetic studies revealed an extended plasma elimination half-life for the charge-reversible nanocarriers,and antitumor efficacy studies demonstrated superior tumor suppression with minimal systemic toxicity.This research underscores the potential of integrating charge-reversal and responsive release mechanisms into one nanocarrier system,balancing the long circulation and high tumor cell internalization capacity of the nanocarrier,and providing a promising strategy for targeted delivery of nanomedicine.展开更多
The inherent low immunogenicity and immunosuppressive metabolism of solid tumors significantly attenuate the immunotherapeutic effect and restrict the immune response.In this work,an endoplasmic reticulum(ER)targeting...The inherent low immunogenicity and immunosuppressive metabolism of solid tumors significantly attenuate the immunotherapeutic effect and restrict the immune response.In this work,an endoplasmic reticulum(ER)targeting photodynamic oxidizer(designated as PhotoOx)is fabricated to boost the antitumor immunity by integrating photodynamic therapy(PDT)induced immunogenic cell death(ICD)with indoleamine 2,3-dioxygenase 1(IDO1)inhibition.Among which,an ER targeting photosensitizer-peptide conjugate called PhotoPe is rationally designed for optimal functionality and amphiphilicity,which could self-assemble into nano-micelles co-delivering chlorin e6 and NLG919.PhotoOx exhibits a good stability to enable ER targeting drug delivery,which could induce ER rupture to intensify PDT induced ICD and release damage associated molecular patterns(DAMPs).Furthermore,PhotoOx could effectively initiate immunological cascades,leading to the suppression of regulatory T cells(Tregs)and activation of CD8^(+)T cells when combines with IDO inhibition.Furthermore,the multi-synergistic effects of PhotoOx activate a robust systemic anti-tumor immune response,resulting in the eradication of lung and liver metastases.Such a medication strategy might inspire the rational design of biomedicine for precise drug delivery,which also provides a sophisticated mechanism for addressing the challenges of solid tumor treatment.展开更多
Gliomas are the most common intracranial tumors with poor survival and high mortality.Furthermore,the clinical efficacy of current drugs is still not ideal;despite the development of several therapeutic drugs over the...Gliomas are the most common intracranial tumors with poor survival and high mortality.Furthermore,the clinical efficacy of current drugs is still not ideal;despite the development of several therapeutic drugs over the past decades and tumor progression or recurrence is inevitable in many patients.RNAibased therapy presents a novel disease-related gene targeting therapy,including otherwise undruggable genes,and generates therapeutic options.However,the therapeutic effect of siRNA is hindered by multiple biological barriers,primarily the blood-brain barrier(BBB).A glycoprotein-derived peptide-mediated delivery system is the preferred option to resolve this phenomenon.RDP,a polypeptide composed of 15 amino acids derived from rabies virus glycoprotein(RVG),possesses an N-type acetylcholine receptor(nAChR)-binding efficiency similar to that of RVG29.Given its lower cost and small particle size when used as a ligand,RDP should be extensively evaluated.First,we verified the brain-targeting efficacyy of RDP at the cellular and animal levels and further explored the possibility of using the RDP-oligoarginine peptide(designated RDP-5R)as a bio-safe vehicle to deliver therapeutic siRNA into glioma cells in vitro and in vivo.The polypeptide carrier possesses a diblock design composed of oligoarginine for binding siRNA through electrostatic interactions and RDP for cascade BBB-and glioma cell-targeting.The results indicated that RDP-R5/siRNA nanoparticles exhibited stable and suitable physicochemical properties for in vivo application,desirable glioma-targeting effects,and therapeutic efficiency.As a novel and efficient polypeptide carrier,RDP-based polypeptides hold great promise as a noninvasive,safe,and efficient treatment for various brain diseases.展开更多
文摘The published article titled“MicroRNA-133b Inhibits Proliferation,Cellular Migration,and Invasion via Targeting LASP1 in Hepatocarcinoma Cells”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1269–1282.
文摘Oncology Research Editorial Office Published:19 January 2026 The published article titled“miR-202 Promotes Cell Apoptosis in Esophageal Squamous Cell Carcinoma by Targeting HSF2”has been retracted from Oncology Research,Vol.25,No.2,2017,pp.215-223.DOI:10.3727/096504016X14732772150541 URL:https://www.techscience.com/or/v25n2/56800.
文摘Oncology Research Editorial Office Published:19 January 2026 The published article titled“miR-126-5p Restoration Promotes Cell Apoptosis in Cervical Cancer by Targeting Bcl2l2”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.463-470.DOI:10.3727/096504016X14685034103879 URL:https://www.techscience.com/or/v25n4/56826.
文摘Neutrophil extracellular traps(NETs)have emerged as key mediators of cardiovascular diseases(CVDs),linking innate immune activation to vascular injury,thrombosis,and maladaptive remodeling.This review synthesizes recent insights into the molecular and cellular pathways driving NET formation,including post-translational modifications,metabolic reprogramming,inflammasome signaling,and autophagy.It highlights the role of NETs in atherosclerosis,thrombosis,myocardial ischemia-reperfusion injury,and hypertension,emphasizing common control points such as peptidylarginine deiminase 4(PAD4)-dependent histone citrullination and nicotinamide adenine dinucleotide phosphate oxidases 2(NOX2)-mediated oxidative stress.Mechanistic interpretation of circulating biomarkers,includingmyeloperoxidase(MPO)-DNA complexes,citrullinated histoneH3,and cell-free DNA,provides a translational bridge between NET biology and patient stratification.Therapeutic strategies targeting NETs are examined through three main approaches:inhibition of NET initiation,enhancement of chromatin clearance,and neutralization of toxic extracellular components,with attention to both established and emerging interventions.In contrast to previous reviews,this study highlights the novelty of a mechano-therapeutic framework by providing a mechanistic roadmap linking NET formation pathways to therapeutic targeting in cardiovascular disease.Moving forward,integrating mechanistic information with biomarker discovery,precision profiling,and targeted therapies offers innovative strategies to reduce vascular inflammation and improve outcomes in cardiovascular disease.
基金supported by Guang Dong Basic and Applied Basic Research Foundation(No.2023B1515120001)Shenzhen University 2035 Program for Excellent Research(Nos.00000208 and 00000225)。
文摘The potential of messenger RNA(m RNA)as a therapeutic tool for treating diseases has garnered considerable interest,especially in the wake of the successful creation of m RNA vaccines to counter corona virus disease 2019(COVID-19).Nucleic acid-based drug gene therapies have emerged as exceptionally promising avenues for combating disease.Furthermore,lipid nanoparticles(LNPs)are ideal carriers for nucleic acid delivery owing to their ionic nature,which enables nucleic acids to electrostatically interact with intracellular membranes,thereby promoting efficient intracellular nucleic acid release.Unfortunately,the effectiveness of LNPs in targeting organs beyond the liver is relatively poor.Thus,enhanced extrahepatic targeting is another important property that would lead to improved in vivo delivery by LNPs.This review focuses on the fundamental characteristics and functions of LNPs developed to facilitate cellular uptake and ensure effective intracellular release of m RNAs.Promising applications,possible advantages and potential challenges associated with use of LNPs in organ specific delivery and release of m RNAs are summarized.Furthermore,the need for future research to address limitations of currently developed LNPs for clinical applications of the m RNA technology is emphasized.
文摘In recent years,proteolysis-targeting chimeras(PROTACs)have gained widespread attention as an emerging therapeutic approach.PROTACs are bifunctional molecules composed of a target protein-binding ligand,an E3 ubiquitin ligase ligand,and a linker connecting these ligands.By harnessing the cell’s intrinsic ubiquitin-proteasome system(UPS),they promote the ubiquitination of specific target proteins,leading to their degradation and therapeutic effects.PROTACs show exceptional promise in targeting conventional“undruggable”targets compared to traditional small-molecule inhibitors.This review provides an overview of PROTACs,including their molecular mechanism of action,therapeutic benefits,development history,key design aspects,current research and development challenges,and future trends in nextgeneration PROTAC technology.
基金supported by a grant from the Dalian Science and Technology Innovation Fund Program(No.2024JJ13PT070)United Foundation for Dalian Institute of Chemical Physics,Chinese Academy of Sciences and the Second Hospital of Dalian Medical University(No.DMU-2&DICP UN202410)Dalian Life and Health Field Guidance Program Project(No.2024ZDJH01PT084).
文摘Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensively explores how cancer cells rewire BCAA metabolism to enhance proliferation,survival,and therapy resistance.Tumors manipulate BCAA uptake and catabolism via high expression of transporters like L-type amino acid transporter 1(LAT1)and enzymes including branched chain amino acid transaminase 1(BCAT1),branched chain amino acid transaminase 2(BCAT2),branched-chain alpha-keto acid dehydrogenase(BCKDH),and branched chain alpha-keto acid dehydrogenase kinase(BCKDK).These alterations sustain energy production,biosynthesis,redox homeostasis,and oncogenic signaling(especially mammalian target of rapamycin complex 1[mTORC1]).Crucially,tumor-driven BCAA depletion also shapes an immunosuppressive microenvironment,impairing anti-tumor immunity by limiting essential nutrients for T cells and natural killer(NK)cells.Innovative therapeutic strategies targeting BCAA pathways—ranging from selective small-molecule inhibitors(e.g.,LAT1 and BCAT1/2)to dietary modulation—have shown promising preclinical and early clinical efficacy,highlighting their potential to exploit metabolic vulnerabilities in cancer cells while bolstering immune responses.By integrating multi-omics data and precision targeting approaches,this review underscores the translational significance of BCAA metabolic reprogramming,positioning it as a novel frontier in cancer treatment.
基金the Project of China-Japan Joint International Laboratory of Advanced Drug Delivery System Research and Translation of Liaoning Province(No.2024JH2/102100007)the open fund of National Key Laboratory of Advanced DrugFormulations for Overcoming Delivery Barriers(No.2024-KFB-003)+1 种基金the National Natural Science Foundation of China(No.82104109)Scientific Research Project of Liaoning Department of Education(No.LJ212410163045).
文摘Cancer is the second leading cause of death globally.Its treatment remains a major challenge due to the disease's complexity,heterogeneity,and adaptive nature.Among the array of available treatments,targeted therapy emerges as a paramount approach to address this substantial unmet clinical need,owing to its precise tumor targeting capabilities and potential for mitigating tumor progression risks.Drug conjugates are in high demand for targeted therapy due to their unique ligand specificity and potent cytotoxicity,thereby significantly enhancing therapeutic efficacy and reducing the incidence of adverse effects.Therefore,as a burgeoning field in biomedical research,it is timely to outline the latest advances in drug conjugates-driven cancer treatment.Herein,we aim to present the emerging breakthroughs in this exciting field at the intersection of target ligands,linkers,payloads,and cancer treatments.This review focuses on several drug conjugates-related strategies,including antibody-drug conjugates(ADCs),peptide-drug conjugates(PDCs),small molecule-drug conjugates(SMDCs),aptamer-drug conjugates(ApDCs)and radionuclide-drug conjugates(RDCs).Finally,we discuss the fundamentals behind drug conjugate-based anticancer therapeutics,along with their inherent advantages and associated challenges,as well as recent research advances.
基金supported by the financial assistance from Natural Science Fund Project of Science and Technology Department of Jilin Province (Nos.YDZJ202301ZYTS141,YDZJ202501ZYTS793)。
文摘Hepatic fibrosis is regulated by the synergistic actions of various cells and cytokines,with the activation and proliferation of hepatic stellate cells(HSCs) being considered the central event in this process.To achieve specific targeting of activated hepatic stellate cells(a HSCs) and precise treatment of hepatic fibrosis,this study developed a dual-functional drug delivery system(SIL/c RGD-PEG-PPS PMs) with both targeting and responsive release capabilities.It aims to target the αvβ 3 receptor specifically expressed on the surface of a HSCs using the cyclic peptide c(RGDyk),and to exploit the high reactive oxygen species(ROS) level in the cellular microenvironment to achieve concentrated burst release of drugs at the pathological sites of hepatic fibrosis.Based on multiple assessments,SIL/c RGD-PEG-PPS PMs specifically enhanced the targeted delivery of silybin(SIL) to a HSCs,inhibited the proliferation and migration of a HSCs,and exhibited good biosafety.Additionally,it demonstrated excellent anti-fibrotic activity in fibrotic mice.In summary,this study shows great potential in targeted treatment of hepatic fibrosis and provides a multifunctional tool for advancing the research and therapeutic strategies of hepatic fibrosis.
文摘Peripheral immunity forms the foundation of tumor immunity,while tumor immunity represents a more refined adaptation of peripheral immune responses.The tumor microenvironment(TME),a localized niche surrounding tumor cells,is inherently immunosuppressive(1,2).Effective tumor therapy necessitates the dismantling of this microenvironment,aiming to eradicate tumors from the host system.
基金support from the National Natural Science Foundation of China(Nos.22277056,21977052)the Distinguished Young Scholars of Jiangsu Province(No.BK20230006)+2 种基金the Natural Science Foundation of Jiangsu Province(Nos.BK20230977,BK20231090)the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(No.23KJB150020)the Jiangsu Excellent Postdoctoral Program(No.2022ZB758)。
文摘Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.
文摘Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ability,the arginine-glycine-aspartic(RGD)peptide and the epidermal growth factor receptor interference(EGFRi)peptide were fused with MAP30,which was named ELRL-MAP30.The efficiency of targeted therapy for triple-negative breast cancer(TNBC)MDA-MB-231 cells,which lack the expression of estrogen receptor(ER),Progesterone receptor(PgR)and human epidermal growth factor receptor-2(HER2),is limited.In this study,we focus on exploring the effect and mechanism of ELRL-MAP30 on TNBC MDA-MB-231 cells.First,we discovered that ELRL-MAP30 significantly inhibited the migration and invasion of MDA-MB-231 cells and induced MDA-MB-231 cell apoptosis.Moreover,ELRL-MAP30 treatment resulted in a significant increase in Bax expression and a decrease in Bcl-2 expression.Furthermore,ELRL-MAP30 triggered apoptosis via the Fak/EGFR/Erk and Ilk/Akt signaling pathways.In addition,recombinant ELRL-MAP30 can inhibit chicken embryonic angiogenesis,and also inhibit the tube formation ability of human umbilical vein endothelial cells(HUVECs),indicating its potential therapeutic effects on tumor angiogenesis.Collectively,these results indicate that ELRL-MAP30 has significant tumor-targeting properties in MDA-MB-231 cancer cells and reveals potential therapeutic effects on angiogenesis.These findings indicate the potential role of ELRL-MAP30 in the targeted treatment of the TNBC cell line MDA-MB-231.
文摘The published article titled“Overexpression of miR-1283 Inhibits Cell Proliferation and Invasion of Glioma Cells by Targeting ATF4”has been retracted from Oncology Research,Vol.27,No.3,2019,pp.325–334.
文摘The published article titled“Swainsonine inhibits invasion and the EMT process in esophageal carcinoma cells by targeting twist1”has been retracted from Oncology Research,Vol.26,No.8,2018,pp.1207–1213.
文摘The published article titled“MicroRNA-133b Inhibits Cell Proliferation and Invasion in Osteosarcoma by Targeting Sirt1”has been retracted from Oncology Research,Vol.25,No.9,2017,pp.1421–1430.
基金the National Key Research and Development Program of China(2023YFD1700500)the College Student Research Training Program(202110307002T)Bayer Grants4Ag Initiative for their support.
文摘Developing novel anti-infective drugs is essential to combat antimicrobial resistance,address emerging pathogens,and safeguard global health against evolving infectious threats.A recent publication in the esteemed journal Nature by Qisen Deng et al.reported on the comprehensive evaluation of the therapeutic efficacy of mandimycin against multidrug-resistant(MDR)fungal pathogens.The polyene macrolide antifungal antibiotic,mandimycin,was discovered using a phylogeny-guided natural-product discovery platform.Authors utilized various in vivo mouse models such as systemic and soft-tissue infections to assess the antifungal activity of mandimycin.The efficacy was measured by quantifying the fungal burden in major organs and assessing survival rates.In systemic infections,mandimycin demonstrated significant dose-dependent antifungal efficacy,as compared to amphotericin B,particularly in cases where the latter was ineffective against MDR C.auris.Furthermore,mandimycin showed a favorable safety profile,with low toxicity and no observed side effects at effective doses.The study's findings contribute valuable insights into the potential of mandimycin as a novel antifungal agent,offering hope for improved treatment options against challenging fungal infections.The results pave the way for further research and clinical applications in the fight against antifungal resistance.
基金support by the National Key R&D Program of China(Grant No.2020YFA0909000)National Natural Science Foundation of China(Grant Nos.62235007 and 22204070)+2 种基金Shenzhen Science and Technology Program(Grant Nos.KQTD20170810111314625,JCYJ20210324115807021,and SGDX20211123114002003)Shenzhen Bay Laboratory(SZBL 2021080601002)Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022 B1212010003).
文摘Nanobodies have been extensively demonstrated in biomedical imaging and therapy. However, nanobody probes often suffer from rapid renal clearance due to its small size. Herein, we reported a recombinant nanobody with a 200 amino-acid polypeptide chain consisting of Pro, Ala, and Ser (PAS) at the C-terminal, which can be easily expressed in Escherichia coli with a high yield. The PASylated nanobody was functionalized with a fluorescent dye and the cell labeling properties were characterized by flow cytometry and confocal microscopy. In vivo fluorescence imaging indicated that the PASylated nanobody showed comparable blood circulation time, but ∼1.5 times higher tumor targeting ability as compared to the PEGylated nanobody of comparable molecular weight. Our findings demonstrate that nanobody PASylation is a promising approach to produce long-circulating nanobody probes for imaging and therapeutic applications.
基金supported by the Natural Science Foundation of Jilin Province(No.20240101003JJ)the National Natural Science Foundation of China(Nos.22275065,52073116)。
文摘Nanomedicine holds considerable promise for advancing cancer therapy,however,effective delivery of drugs to solid tumors remains a challenge due to rapid systemic clearance and inefficient cellular uptake.Herein,we have developed a novel charge-reversible nanogel to deliver paclitaxel(PTX)dimers(DPP)with enhanced stability and targeting precision.The nanogels exhibit a dynamic charge-reversal mechanism responsive to the acidic tumor microenvironment(TME),optimizing the cellular uptake of prodrugs.In the high glutathione(GSH)conditions within cancer cells,the disulfide bonds in the DPP are cleaved,resulting in the intracellular release of active PTX and reduced drug toxicity to normal cells.In vivo pharmacokinetic studies revealed an extended plasma elimination half-life for the charge-reversible nanocarriers,and antitumor efficacy studies demonstrated superior tumor suppression with minimal systemic toxicity.This research underscores the potential of integrating charge-reversal and responsive release mechanisms into one nanocarrier system,balancing the long circulation and high tumor cell internalization capacity of the nanocarrier,and providing a promising strategy for targeted delivery of nanomedicine.
基金supported by the National Natural Science Foundation of China(No.32371394)the National Key R&D Program of China(No.2021YFD1800600)+3 种基金the Special Projects in Key Areas of Colleges and Universities in Guangdong Province(No.2022ZDZX2046)the Open Project of State Key Laboratory of Respiratory Disease(No.SKLRD-OP-202502)the Postdoctoral Fellowship Program of CPSF(No.GZC20230619)Postdoctoral startup funding of Guangzhou Medical University(No.Q0301–130)。
文摘The inherent low immunogenicity and immunosuppressive metabolism of solid tumors significantly attenuate the immunotherapeutic effect and restrict the immune response.In this work,an endoplasmic reticulum(ER)targeting photodynamic oxidizer(designated as PhotoOx)is fabricated to boost the antitumor immunity by integrating photodynamic therapy(PDT)induced immunogenic cell death(ICD)with indoleamine 2,3-dioxygenase 1(IDO1)inhibition.Among which,an ER targeting photosensitizer-peptide conjugate called PhotoPe is rationally designed for optimal functionality and amphiphilicity,which could self-assemble into nano-micelles co-delivering chlorin e6 and NLG919.PhotoOx exhibits a good stability to enable ER targeting drug delivery,which could induce ER rupture to intensify PDT induced ICD and release damage associated molecular patterns(DAMPs).Furthermore,PhotoOx could effectively initiate immunological cascades,leading to the suppression of regulatory T cells(Tregs)and activation of CD8^(+)T cells when combines with IDO inhibition.Furthermore,the multi-synergistic effects of PhotoOx activate a robust systemic anti-tumor immune response,resulting in the eradication of lung and liver metastases.Such a medication strategy might inspire the rational design of biomedicine for precise drug delivery,which also provides a sophisticated mechanism for addressing the challenges of solid tumor treatment.
基金supported by CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-026,China).
文摘Gliomas are the most common intracranial tumors with poor survival and high mortality.Furthermore,the clinical efficacy of current drugs is still not ideal;despite the development of several therapeutic drugs over the past decades and tumor progression or recurrence is inevitable in many patients.RNAibased therapy presents a novel disease-related gene targeting therapy,including otherwise undruggable genes,and generates therapeutic options.However,the therapeutic effect of siRNA is hindered by multiple biological barriers,primarily the blood-brain barrier(BBB).A glycoprotein-derived peptide-mediated delivery system is the preferred option to resolve this phenomenon.RDP,a polypeptide composed of 15 amino acids derived from rabies virus glycoprotein(RVG),possesses an N-type acetylcholine receptor(nAChR)-binding efficiency similar to that of RVG29.Given its lower cost and small particle size when used as a ligand,RDP should be extensively evaluated.First,we verified the brain-targeting efficacyy of RDP at the cellular and animal levels and further explored the possibility of using the RDP-oligoarginine peptide(designated RDP-5R)as a bio-safe vehicle to deliver therapeutic siRNA into glioma cells in vitro and in vivo.The polypeptide carrier possesses a diblock design composed of oligoarginine for binding siRNA through electrostatic interactions and RDP for cascade BBB-and glioma cell-targeting.The results indicated that RDP-R5/siRNA nanoparticles exhibited stable and suitable physicochemical properties for in vivo application,desirable glioma-targeting effects,and therapeutic efficiency.As a novel and efficient polypeptide carrier,RDP-based polypeptides hold great promise as a noninvasive,safe,and efficient treatment for various brain diseases.
