Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of ...Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of life and restrict therapeutic outcomes.Addressing this pressing issue,this review presents a thorough and systematic analysis of innovative and emerging strategies designed to minimize the toxicity induced by treatment,while maintaining or even enhancing antitumor efficacy.The focus is on six promising therapeutic approaches:combination therapies utilizing natural bioactive products,molecularly targeted therapies,immunotherapies,nanotechnology-mediated drug delivery systems,adjunct traditional Chinese medicine interventions,and low-dose spatiotemporally concerted regimens.Each approach employs unique mechanisms—such as enhanced targeting precision,immune system activation,tumor microenvironment reprogramming,and multi-component synergistic effects—to mitigate damage to normal tissues and reduce systemic adverse reactions.Despite promising preclinical and clinical advancements,several challenges persist,including drug resistance,high economic costs,a lack of reliable predictive biomarkers,and complexities in clinical translation and regulatory approval.Looking ahead,the incorporation of artificial intelligence,multi-omics profiling,and novel biomimetic nanotechnologies offers unprecedented opportunities for developing highly personalized,low-toxicity treatment frameworks.This review highlights a fundamental shift in oncology towards precision medicine that balances efficacy with safety,demonstrating the transformative potential of these strategies in shaping the future of cancer therapy and enhancing patient care globally.展开更多
An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(C...An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(Ce6)and triethoxy(1H,1H,2H,2H‑nonafluorohexyl)silane(TFS)was coated on the outer layer of UC,and then a layer of HKUST‑1 shell was coated.The obtained nanocomposite UC@Ce6/TFS@mSiO_(2)@HKUST‑1(noted as UCTSH)was used for the synergistic treatment of chemodynamic therapy(CDT)and photodynamic therapy(PDT).Interestingly,the nanostructures can specifically re lease Cu^(2+)in the acidic tumor microenvironment.Cu^(2+)reacts with excess hydrogen peroxide(H_(2)O_(2))in the tumor microenvironment to form cytotoxic hydroxyl radical.Secondly,Ce6,with the action of oxygen‑carrying TFS,selectively produces a large amount of singlet oxygen by 808 nm laser irradiation.UCTSH can enhance the anti‑tumor effects of PDT and CDT by increasing the production level of reactive oxygen species,without causing damage to normal cells.展开更多
BACKGROUND Chemotherapy-induced cardiotoxicity is a significant complication in cancer therapy,limiting treatment efficacy and worsening patient outcomes.Recent studies have implicated the gut microbiome and its key m...BACKGROUND Chemotherapy-induced cardiotoxicity is a significant complication in cancer therapy,limiting treatment efficacy and worsening patient outcomes.Recent studies have implicated the gut microbiome and its key metabolites,such as shortchain fatty acids(SCFAs)and trimethylamine-N-oxide(TMAO),in mediating inflammation,oxidative stress,and cardiac damage.The gut-heart axis is increasingly recognized as a pivotal pathway linking microbiota dysregulation to chemotherapy-related cardiac dysfunction.AIM To systematically review existing evidence on the role of gut microbiome alterations in chemotherapy-induced cardiotoxicity and evaluate emerging microbiome-based therapeutic strategies aimed at mitigating cardiovascular risk in cancer patients.METHODS A systematic literature search was conducted in PubMed,Scopus,and Web of Science for studies published between January 2013 and December 2024.Studies were included if they examined chemotherapy-induced cardiotoxicity in relation to gut microbiota composition,microbial metabolites(e.g.,SCFAs,TMAO),or microbiome-targeted interventions.Selection followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data extraction focused on microbiota alterations,mechanistic pathways,cardiac outcomes,and quality assessments using standardized risk-of-bias tools.RESULTS Eighteen studies met the inclusion criteria.Chemotherapy was consistently associated with gut dysbiosis characterized by reduced SCFA-producing bacteria and increased TMAO-producing strains.This imbalance contributed to gut barrier disruption,systemic inflammation,and oxidative stress,all of which promote myocardial damage.SCFA depletion weakened anti-inflammatory responses,while elevated TMAO levels exacerbated cardiac fibrosis and dysfunction.Preclinical studies showed promising cardioprotective effects from probiotics,prebiotics,dietary interventions,and fecal microbiota transplantation,though human data remain limited.CONCLUSION Gut microbiome dysregulation plays a crucial role in the development of chemotherapy-induced cardiotoxicity.Altered microbial composition and metabolite production trigger systemic inflammation and cardiac injury.Microbiome-targeted therapies represent a promising preventive and therapeutic approach in cardio-oncology,warranting further clinical validation through well-designed trials.展开更多
Bone fractures represent a significant global healthcare burden.Although fractures typically heal on their own,some fail to regenerate properly,leading to nonunion,a condition that causes prolonged disability,morbidit...Bone fractures represent a significant global healthcare burden.Although fractures typically heal on their own,some fail to regenerate properly,leading to nonunion,a condition that causes prolonged disability,morbidity,and mortality.The challenge of treating nonunion fractures is further complicated in patients with underlying bone disorders where systemic and local factors impair bone healing.Traditional treatment approaches,including autografts,allografts,xenografts,and synthetic biomaterials,face limitations such as donor site pain,immune rejection,and insufficient mechanical strength,underscoring the need for alternative strategies.Biologic therapies have emerged as promising tools to enhance bone regeneration by leveraging the body’s natural healing processes.This review explores the critical role of conventional and emerging biologics in fracture healing.We categorize biologic therapies into protein-based treatments,gene and transcript therapies,small molecules,peptides,and cell-based therapies,highlighting their mechanisms of action,advantages,and clinical relevance.Finally,we examine the potential applications of biologics in treating fractures associated with bone disorders such as osteoporosis,osteogenesis imperfecta,rickets,osteomalacia,Paget’s disease,and bone tumors.By integrating biologic therapies with existing biomaterial-based strategies,these innovative approaches have the potential to transform clinical management and improve outcomes for patients with difficult-to-heal fractures.展开更多
Novel antibacterial strategies such as antibacterial photodynamic therapy(aPDT)and photothermal therapy(PTT)have gained significant attention,however,relying on a single-treatment approach still faces challenges of in...Novel antibacterial strategies such as antibacterial photodynamic therapy(aPDT)and photothermal therapy(PTT)have gained significant attention,however,relying on a single-treatment approach still faces challenges of insufficient therapeutic efficiency and the potential for drug resistance.In this study,a multimodal synergistic antibacterial nanoplatform by coupling a carbon monoxide(CO)donor(4-(3-hydroxy-4-oxo-4H-chromen-2-yl)benzoic acid(4-BA))with carbon dots(CDs)is developed,referred to as CDs-CO,which integrates multiple antibacterial modes of aPDT,PTT,and gas therapy.This nanoplatform is designed for highly efficient antibacterial action with a low risk of inducing drug resistance.CDs are engineered to possess tailored functions,including deep-red light-triggered heat and singlet oxygen(^(1)O_(2))production.After modification with 4-BA and exposure to 660 nm laser irradiation,CDs-CO exhibits favorable photothermal conversion efficiency(η=52.7%),robust ^(1)O_(2) generation,and ^(1)O_(2)-activated CO release.Antibacterial experiments demonstrated the excellent sterilization effects of CDs-CO against both Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus),underscoring the enhanced antibacterial efficiency of this multimodal nanoplatform.This study offers a rational approach for designing multimodal synergistic antibacterial platforms,highlighting their potential for effectively treating bacterial infections.展开更多
Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary in...Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary intervention and statins,reduce major adverse cardiovascular events(MACE)by 25%-30%,yet a 20%five-year MACE risk persists in high-risk cohorts.These approaches,histor-ically focused on luminal stenosis,fail to address systemic atherogenesis drivers like endothelial dysfunction and inflammation.Specifically,dietary linoleic acid restriction(<5 g/day)reduces oxidized low-density lipoprotein by approximately 15%by limiting peroxidation-prone bisallylic bonds,mitigating arterial inflam-mation,a key atherogenic trigger.Enhanced external counterpulsation,through pulsatile shear stress,enhances nitric oxide-mediated coronary perfusion,alle-viating angina in approximately 70%of refractory cases unresponsive to revascu-larization.Nanoparticle-facilitated chelation targets atherosclerotic plaques with precision,reducing calcium content by up to 30%in preclinical models,offering a novel avenue for lesion reversal.These innovations collectively address residual risk by tackling root causes,oxidative stress,endothelial dysfunction,and plaque instability,potentially halving MACE rates with widespread adoption.Despite promising preliminary data,gaps remain in long-term safety and scalability.Robust clinical trials are needed to validate these approaches,which collectively aim to transform cardiovascular disease management by prioritizing prevention and vascular restoration,potentially reducing coronary events to a public health rarity.展开更多
Metal-organic frameworks(MOFs)with high porosity,specific surface area,and unique topologies are highly regarded for their applications in photocatalysis,medical treatment,and environmental pollutant degradation.Howev...Metal-organic frameworks(MOFs)with high porosity,specific surface area,and unique topologies are highly regarded for their applications in photocatalysis,medical treatment,and environmental pollutant degradation.However,due to the limitations of the tumor microenvironment(TME),traditional MOFs have limited efficacy in this environment.This paper designs multi-metal oxide-based heterostructure POMOFs nanoreactors with a nesting doll-like structure.This new structure not only exhibits therapeutic effects in TME but also utilizes ultrasound(US)to enhance the release of reactive oxygen species(ROS)for CDT&SDT co-therapy,becoming an effective sound sensitizer for destroying tumor cells.In summary,our study proposes an idea for constructing multi-metal oxide-based heterostructure MOFs nanoreactors material with a nesting doll-like structure to enhance ROS release and synergistically treat tumor diseases.展开更多
Despite remarkable advances in nanomedicine,localized delivery of advanced cancer therapeutics remains underexploited.Advanced therapies based on biopharmaceuticals,immunotherapy,or gene therapy have revolutionized on...Despite remarkable advances in nanomedicine,localized delivery of advanced cancer therapeutics remains underexploited.Advanced therapies based on biopharmaceuticals,immunotherapy,or gene therapy have revolutionized oncology.Yet,their systemic administration is often associated with limitations such as poor sitespecific accumulation,instability,and systemic toxicity.Hydrogels/macrogels offer the ability to encapsulate,protect,and release biomolecules in situ with sustained and stimulus-responsive profiles,addressing key translational gaps.This review provides a focused synthesis of the last five years of hydrogel-based research for cancer therapy,with emphasis on peptides,antibodies,immunotherapeutic agents,and gene delivery systems.We discuss design principles,release mechanisms,and clinical translation challenges,highlighting structure-function relationships and comparative performance across therapeutic classes.By integrating mechanistic insights with recent breakthroughs,we outline how next-generation hydrogels can synergize with personalized medicine and combination therapies to redefine localized cancer treatment.This work explores the fundamental aspects and provides examples of hydrogel-based delivery for the advanced treatment of cancer.The review summarizes the dynamic landscape of hydrogel research of the last 5 years,showcasing their potential systems for the precise delivery of biomolecules.Specifically,we explore the multidimensional role of hydrogels in the sustained and localized release of antibodies,immunotherapeutic agents,and genes as next-generation platforms for localized cancer treatment.This review aims to critically evaluate the mechanisms and applications of these systems in order to assess their potential to transform medical interventions and advance patient care.展开更多
In recent years,multidisciplinary treatment strategies have profoundly improved drug responses and survival outcomes of breast cancer(BC)patients.However,there is an urgent need for novel therapies for BC patients who...In recent years,multidisciplinary treatment strategies have profoundly improved drug responses and survival outcomes of breast cancer(BC)patients.However,there is an urgent need for novel therapies for BC patients who are heavily treated or develop resistance to conventional treatment regimens.Radionuclide therapy(RT)and targeted radionuclide therapy(TRT)have emerged as paradigm-shifting therapeutic approaches for BC,which enable functions of both imaging and localised treatment.They utilise radionuclides that can selectively bind to biomarkers overexpressing on BC cells,allowing precise delivery and localised tumour irradiation.Moreover,several types of radionuclides possess‘cross-fire’effects that result in the eradication of neighbouring tumour cells lacking the biomarker expression.In the current review,we summarise the potential biomarkers for the development of RT and TRT that can be employed in the treatment of BC,including receptor markers of ER,PR and HER2,together with other markers of Trop2,PD-1,EGFR,GRPR and PSMA.展开更多
Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major coh...Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major cohort for stem cell-based therapies.However,the regenerative potential of stem cells significantly decreases with advanced age and deteriorating health status of the donor.Therefore,the efficacy of autologous stem cell therapy is significantly compromised in older patients.To overcome these limitations,alternative strategies have been used to restore the age-and disease-depleted function of stem cells.These methods aim to restore the therapeutic efficacy of aged stem cells for autologous use.This article explores the effect of donor age and health status on the regenerative potential of stem cells.It further highlights the limitations of stem cell-based therapy for autologous treatment in the elderly.A comprehensive insight into the potential strategies to address the“age”and“disease”compromised regenerative potential of autologous stem cells is also presented.The information provided here serves as a valuable resource for physicians and patients for optimization of stem cellbased autologous therapy for aged patients.展开更多
Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,ta...Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,tau is not an easy target because it dynamically interacts with microtubules and other cellular components,which presents a challenge for tau-targeted drugs.New cellular models could aid the development of mechanism-based tau-targeted therapies.展开更多
Therapy discontinuation in inflammatory bowel disease,particularly involving immunomodulators,biologics,and small molecules,remains a controversial and evolving topic.This letter reflects on developments following the...Therapy discontinuation in inflammatory bowel disease,particularly involving immunomodulators,biologics,and small molecules,remains a controversial and evolving topic.This letter reflects on developments following the publication by Meštrovićet al,emphasizing the complex balance between risks of relapse,antidrug antibody formation,and potential complications of long-term immunosuppression.Recent evidence underscores high relapse rates following withdrawal-especially of anti-tumor necrosis factor agents-and highlights the lack of robust data for newer biologics.Updated guidelines from European Crohn’s and Colitis Organization,British Society of Gastroenterology,and American College of Gastroenterology all support cautious and individualized approaches,with strict criteria and close follow-up,particularly in Crohn’s disease.For ulcerative colitis,therapeutic cycling remains insufficiently addressed.We proposed a flowchart to support clinical decision-making and stress the importance of shared decisionmaking in the era of personalized medicine since,despite new drug classes and evolving strategies,the therapeutic ceiling in inflammatory bowel disease has yet to be fully overcome.展开更多
Tumors pose a serious threat to human life and health. In recent years, gene therapy against tumors has garnered considerable attention. Small interfering RNAs(siRNAs), an important class of nucleic acid drugs, can si...Tumors pose a serious threat to human life and health. In recent years, gene therapy against tumors has garnered considerable attention. Small interfering RNAs(siRNAs), an important class of nucleic acid drugs, can silence the m RNAs of tumor-associated genes with high specificity through RNA interference(RNAi), inhibiting tumor-related signaling pathways or protein expression and thereby exerting anti-tumor effects. However, antitumor siRNA drugs are currently in the clinical research stage, and none of these drugs have been approved for marketing, mainly because of the challenges in terms of safety,efficacy and targeted delivery. Nano-delivery systems can enhance siRNA stability and improve siRNA pharmacokinetics and biodistribution, while increasing their uptake by target cells to achieve precise delivery and controlled release, thereby serving as a promising solution to overcome the challenges of siRNA drug application. This review summarizes the existing research on the nano-delivery systems currently available to help siRNAs achieve organ-targeted delivery and enhance the anti-tumor efficacy of siRNAs, discussing the characteristics of siRNA action and the unique advantages of different types of nanodelivery systems. The aim was to provide novel ideas for the design and optimization of siRNA-based drug delivery and the development of novel anti-tumor formulations to promote the clinical translation and application of siRNA drugs.展开更多
KRAS is a critical proto-oncogene and molecular switch that is frequently mutated in human cancers.Oncogenic mutations,primarily at codons 12,13,and 61,lock KRAS into a GTPbound active state,thus resulting in constitu...KRAS is a critical proto-oncogene and molecular switch that is frequently mutated in human cancers.Oncogenic mutations,primarily at codons 12,13,and 61,lock KRAS into a GTPbound active state,thus resulting in constitutive signaling through downstream effectors such as RAF and phosphoinositide 3-kinase(PI3K)1.These alterations are highly prevalent in pancreatic cancer,colorectal cancer(CRC),and non-small cell lung cancer(NSCLC),and they drive tumor initiation,progression,and therapy resistance.展开更多
Diatoms,as natural sources of porous silica,have important potential for biomedical applications.Biohybrid microrobots also show promise for targeted delivery;however,research on converting diatoms into biohybrid micr...Diatoms,as natural sources of porous silica,have important potential for biomedical applications.Biohybrid microrobots also show promise for targeted delivery;however,research on converting diatoms into biohybrid microrobots and exploiting their intrinsic properties for cancer treatment remains limited.In this study,Thalassiosira weissflogii was transformed into biohybrid microrobots(Mag-Diatoms)while retaining its natural chlorophyll,thereby enabling Mag-Diatom-mediated photodynamic therapy(PDT)without additional drug modification.In this system,Mag-Diatoms act ed as microrobots,and their intrinsic chlorophyll serve d as a photosensitizer,exhibiting excellent biological safety.The autonomous closed-loop motion of the Mag-Diatoms was achieved using an artificial intelligence algorithm,which enabled controlled navigation along a preset trajectory.Mag-Diatoms also exhibited the ability to traverse narrow slits and target cancer cells within a cellular environment.The PDT effect was validated in vitro using human malignant glioblastoma(GBM)cell lines and primary cells derived from patients.The results revealed that the cell viability was closely related to the Mag-Diatom concentration,laser intensity,and irradiation time.Under combined Mag-Diatoms and laser treatment,viability decreased to 19.5%in primary cells and 3.6%in cell line models.Moreover,in vivo experiments using a mouse glioma model revealed that Mag-Diatom-mediated PDT effectively suppressed GBM progression.These findings highlight the potential of diatom-derived biohybrid microrobots,leveraging their natural properties,as a novel material and solution for PDT-based GBM therapy.展开更多
Ischemic stroke therapy has long been dominated by strategies aimed at restoring cerebral blood flow. Yet, accumulating evidence suggests that neuronal survival and functional recovery depend not only on reperfusion, ...Ischemic stroke therapy has long been dominated by strategies aimed at restoring cerebral blood flow. Yet, accumulating evidence suggests that neuronal survival and functional recovery depend not only on reperfusion, but also on the resolution of postischemic immune dysregulation. This study(Chen et al., Prog Biochem Biophys, 2026, 53(3): 697-710. DOI:10.3724/j.pibb.2025.0541) a dvances this emerging paradigm by proposing a therapeutic strategy that integrates lesion-specific delivery with active modulation of the inflammatory microenvironment.展开更多
The clinical management of hypertrophic scars(HSs)remains challenging due to their complex etiology and heterogeneous morphology,underscoring the need for multitarget treatment strategies.In this study,we developed a ...The clinical management of hypertrophic scars(HSs)remains challenging due to their complex etiology and heterogeneous morphology,underscoring the need for multitarget treatment strategies.In this study,we developed a nanocomposite system constructed through the metal-phenolic network-mediated self-assembly of molybdenum polyoxometalate({Mo 154})and epigallocatechin gallate(EGCG),followed by chitosan encapsulation,to generate chitosan-encapsulated{Mo 154}/EGCG(CME)nanoparticles.These nanoparticles were integrated into dissolvable microneedles(CME@MN)to enable transdermal administration.Under near-infrared laser irradiation,CME exhibited a three-pronged therapeutic effect:suppression of collagen overproduction and excessive extracellular matrix(ECM)deposition in human keloid fibroblasts,regulation of proliferation and migration in human umbilical vein endothelial cells,and reprogramming of macrophages toward a proinflammatory M1 phenotype.In vivo,CME@MN patches preferentially accumulated within scar tissue,where they normalized ECM organization,improved collagen fiber rearrangement,and attenuated fibroblast activity through photothermal-enhanced mechanisms while maintaining an excellent safety profile.The CME@MN system represents a potentially transformative approach to HS management by offering a unified platform that simultaneously targets the fibrotic,angiogenic,and inflammatory components of scar pathogenesis.展开更多
Targeted protein degradation(TPD)is an innovative strategy for selectively eliminating pathogenic proteins,enabling precise degradation of once-undruggable targets in cancer therapy.However,current TPD molecules are o...Targeted protein degradation(TPD)is an innovative strategy for selectively eliminating pathogenic proteins,enabling precise degradation of once-undruggable targets in cancer therapy.However,current TPD molecules are often limited by poor tumor targeting and the need for high doses.To overcome these limitations,assembly/disassembly-based TPD systems have been proposed to effectively degrade proteins of interest and enhance therapeutic efficacy.Herein,we summarize the recent advances in such TPD systems and categorize the strategies employed,including nanosphere morphology of assembled TPD systems,nanofiber morphology of assembled TPD systems,carrier-mediated TPD release systems,and stimulus-induced free TPD molecule formation nanosystems.Finally,we outline future directions and identify the remaining challenges in assembly/disassembly-based TPD systems.展开更多
文摘Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of life and restrict therapeutic outcomes.Addressing this pressing issue,this review presents a thorough and systematic analysis of innovative and emerging strategies designed to minimize the toxicity induced by treatment,while maintaining or even enhancing antitumor efficacy.The focus is on six promising therapeutic approaches:combination therapies utilizing natural bioactive products,molecularly targeted therapies,immunotherapies,nanotechnology-mediated drug delivery systems,adjunct traditional Chinese medicine interventions,and low-dose spatiotemporally concerted regimens.Each approach employs unique mechanisms—such as enhanced targeting precision,immune system activation,tumor microenvironment reprogramming,and multi-component synergistic effects—to mitigate damage to normal tissues and reduce systemic adverse reactions.Despite promising preclinical and clinical advancements,several challenges persist,including drug resistance,high economic costs,a lack of reliable predictive biomarkers,and complexities in clinical translation and regulatory approval.Looking ahead,the incorporation of artificial intelligence,multi-omics profiling,and novel biomimetic nanotechnologies offers unprecedented opportunities for developing highly personalized,low-toxicity treatment frameworks.This review highlights a fundamental shift in oncology towards precision medicine that balances efficacy with safety,demonstrating the transformative potential of these strategies in shaping the future of cancer therapy and enhancing patient care globally.
文摘An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(Ce6)and triethoxy(1H,1H,2H,2H‑nonafluorohexyl)silane(TFS)was coated on the outer layer of UC,and then a layer of HKUST‑1 shell was coated.The obtained nanocomposite UC@Ce6/TFS@mSiO_(2)@HKUST‑1(noted as UCTSH)was used for the synergistic treatment of chemodynamic therapy(CDT)and photodynamic therapy(PDT).Interestingly,the nanostructures can specifically re lease Cu^(2+)in the acidic tumor microenvironment.Cu^(2+)reacts with excess hydrogen peroxide(H_(2)O_(2))in the tumor microenvironment to form cytotoxic hydroxyl radical.Secondly,Ce6,with the action of oxygen‑carrying TFS,selectively produces a large amount of singlet oxygen by 808 nm laser irradiation.UCTSH can enhance the anti‑tumor effects of PDT and CDT by increasing the production level of reactive oxygen species,without causing damage to normal cells.
文摘BACKGROUND Chemotherapy-induced cardiotoxicity is a significant complication in cancer therapy,limiting treatment efficacy and worsening patient outcomes.Recent studies have implicated the gut microbiome and its key metabolites,such as shortchain fatty acids(SCFAs)and trimethylamine-N-oxide(TMAO),in mediating inflammation,oxidative stress,and cardiac damage.The gut-heart axis is increasingly recognized as a pivotal pathway linking microbiota dysregulation to chemotherapy-related cardiac dysfunction.AIM To systematically review existing evidence on the role of gut microbiome alterations in chemotherapy-induced cardiotoxicity and evaluate emerging microbiome-based therapeutic strategies aimed at mitigating cardiovascular risk in cancer patients.METHODS A systematic literature search was conducted in PubMed,Scopus,and Web of Science for studies published between January 2013 and December 2024.Studies were included if they examined chemotherapy-induced cardiotoxicity in relation to gut microbiota composition,microbial metabolites(e.g.,SCFAs,TMAO),or microbiome-targeted interventions.Selection followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data extraction focused on microbiota alterations,mechanistic pathways,cardiac outcomes,and quality assessments using standardized risk-of-bias tools.RESULTS Eighteen studies met the inclusion criteria.Chemotherapy was consistently associated with gut dysbiosis characterized by reduced SCFA-producing bacteria and increased TMAO-producing strains.This imbalance contributed to gut barrier disruption,systemic inflammation,and oxidative stress,all of which promote myocardial damage.SCFA depletion weakened anti-inflammatory responses,while elevated TMAO levels exacerbated cardiac fibrosis and dysfunction.Preclinical studies showed promising cardioprotective effects from probiotics,prebiotics,dietary interventions,and fecal microbiota transplantation,though human data remain limited.CONCLUSION Gut microbiome dysregulation plays a crucial role in the development of chemotherapy-induced cardiotoxicity.Altered microbial composition and metabolite production trigger systemic inflammation and cardiac injury.Microbiome-targeted therapies represent a promising preventive and therapeutic approach in cardio-oncology,warranting further clinical validation through well-designed trials.
基金performed as part of the cmRNAbone project funded by the European Union’s Horizon 2020 research and innovation program under the Grant Agreement No 874790。
文摘Bone fractures represent a significant global healthcare burden.Although fractures typically heal on their own,some fail to regenerate properly,leading to nonunion,a condition that causes prolonged disability,morbidity,and mortality.The challenge of treating nonunion fractures is further complicated in patients with underlying bone disorders where systemic and local factors impair bone healing.Traditional treatment approaches,including autografts,allografts,xenografts,and synthetic biomaterials,face limitations such as donor site pain,immune rejection,and insufficient mechanical strength,underscoring the need for alternative strategies.Biologic therapies have emerged as promising tools to enhance bone regeneration by leveraging the body’s natural healing processes.This review explores the critical role of conventional and emerging biologics in fracture healing.We categorize biologic therapies into protein-based treatments,gene and transcript therapies,small molecules,peptides,and cell-based therapies,highlighting their mechanisms of action,advantages,and clinical relevance.Finally,we examine the potential applications of biologics in treating fractures associated with bone disorders such as osteoporosis,osteogenesis imperfecta,rickets,osteomalacia,Paget’s disease,and bone tumors.By integrating biologic therapies with existing biomaterial-based strategies,these innovative approaches have the potential to transform clinical management and improve outcomes for patients with difficult-to-heal fractures.
基金supported by the National Natural Science Foundation of China(No.52173126)China Postdoctoral Science Foundation(No.2024M751152).
文摘Novel antibacterial strategies such as antibacterial photodynamic therapy(aPDT)and photothermal therapy(PTT)have gained significant attention,however,relying on a single-treatment approach still faces challenges of insufficient therapeutic efficiency and the potential for drug resistance.In this study,a multimodal synergistic antibacterial nanoplatform by coupling a carbon monoxide(CO)donor(4-(3-hydroxy-4-oxo-4H-chromen-2-yl)benzoic acid(4-BA))with carbon dots(CDs)is developed,referred to as CDs-CO,which integrates multiple antibacterial modes of aPDT,PTT,and gas therapy.This nanoplatform is designed for highly efficient antibacterial action with a low risk of inducing drug resistance.CDs are engineered to possess tailored functions,including deep-red light-triggered heat and singlet oxygen(^(1)O_(2))production.After modification with 4-BA and exposure to 660 nm laser irradiation,CDs-CO exhibits favorable photothermal conversion efficiency(η=52.7%),robust ^(1)O_(2) generation,and ^(1)O_(2)-activated CO release.Antibacterial experiments demonstrated the excellent sterilization effects of CDs-CO against both Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus),underscoring the enhanced antibacterial efficiency of this multimodal nanoplatform.This study offers a rational approach for designing multimodal synergistic antibacterial platforms,highlighting their potential for effectively treating bacterial infections.
文摘Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary intervention and statins,reduce major adverse cardiovascular events(MACE)by 25%-30%,yet a 20%five-year MACE risk persists in high-risk cohorts.These approaches,histor-ically focused on luminal stenosis,fail to address systemic atherogenesis drivers like endothelial dysfunction and inflammation.Specifically,dietary linoleic acid restriction(<5 g/day)reduces oxidized low-density lipoprotein by approximately 15%by limiting peroxidation-prone bisallylic bonds,mitigating arterial inflam-mation,a key atherogenic trigger.Enhanced external counterpulsation,through pulsatile shear stress,enhances nitric oxide-mediated coronary perfusion,alle-viating angina in approximately 70%of refractory cases unresponsive to revascu-larization.Nanoparticle-facilitated chelation targets atherosclerotic plaques with precision,reducing calcium content by up to 30%in preclinical models,offering a novel avenue for lesion reversal.These innovations collectively address residual risk by tackling root causes,oxidative stress,endothelial dysfunction,and plaque instability,potentially halving MACE rates with widespread adoption.Despite promising preliminary data,gaps remain in long-term safety and scalability.Robust clinical trials are needed to validate these approaches,which collectively aim to transform cardiovascular disease management by prioritizing prevention and vascular restoration,potentially reducing coronary events to a public health rarity.
基金funded by the National Natural Science Foundation of China(Nos.52372264,32271609and 52473109)+2 种基金The Natural Science Foundation of Heilongjiang Province of China(No.LH2023B002)The Fundamental Research Funds for the Central Universities(No.2572023CT12)Undergraduate Training Programs for Innovations by NEFU(No.202310225565)。
文摘Metal-organic frameworks(MOFs)with high porosity,specific surface area,and unique topologies are highly regarded for their applications in photocatalysis,medical treatment,and environmental pollutant degradation.However,due to the limitations of the tumor microenvironment(TME),traditional MOFs have limited efficacy in this environment.This paper designs multi-metal oxide-based heterostructure POMOFs nanoreactors with a nesting doll-like structure.This new structure not only exhibits therapeutic effects in TME but also utilizes ultrasound(US)to enhance the release of reactive oxygen species(ROS)for CDT&SDT co-therapy,becoming an effective sound sensitizer for destroying tumor cells.In summary,our study proposes an idea for constructing multi-metal oxide-based heterostructure MOFs nanoreactors material with a nesting doll-like structure to enhance ROS release and synergistically treat tumor diseases.
基金supported by the Vall d’Hebron Research Institute(PI23/01345)the Networking Research Centre on Bioengineering,Biomaterials,and Nanomedicine(CIBER-BBN),which is financed by the Instituto de Salud Carlos III(ISCIII)with assistance from the European Regional Development Fund(ERDF)+4 种基金supported by ANID FONDECYT REGULAR(Chile)through project No.1250634,and FOVI230019 granted to Esteban Duran-LaraDiana Rafael was supported by Marie Skłodowska-Curie Actions(MSCA-PF ID 101107735),“La Caixa Foundation”(LCF/BQ/PR24/12050008),and ISCIII(PI24/00745)Fernanda Andrade was granted by the Fundación Científica de la Asociación Española Contra el Cáncer(FCAECC Refs.INVES211530DASI and SNRGS247164DASI)“La Caixa Foundation”(HR24-00927).Júlia German-Cortés was granted by the 791 FAECC(PRDBA258393GERM)The authors also thank the denomination of Consolidated group from Generalitat de Catalunya(2021 SGR 01173)granted to the CB-DDT group。
文摘Despite remarkable advances in nanomedicine,localized delivery of advanced cancer therapeutics remains underexploited.Advanced therapies based on biopharmaceuticals,immunotherapy,or gene therapy have revolutionized oncology.Yet,their systemic administration is often associated with limitations such as poor sitespecific accumulation,instability,and systemic toxicity.Hydrogels/macrogels offer the ability to encapsulate,protect,and release biomolecules in situ with sustained and stimulus-responsive profiles,addressing key translational gaps.This review provides a focused synthesis of the last five years of hydrogel-based research for cancer therapy,with emphasis on peptides,antibodies,immunotherapeutic agents,and gene delivery systems.We discuss design principles,release mechanisms,and clinical translation challenges,highlighting structure-function relationships and comparative performance across therapeutic classes.By integrating mechanistic insights with recent breakthroughs,we outline how next-generation hydrogels can synergize with personalized medicine and combination therapies to redefine localized cancer treatment.This work explores the fundamental aspects and provides examples of hydrogel-based delivery for the advanced treatment of cancer.The review summarizes the dynamic landscape of hydrogel research of the last 5 years,showcasing their potential systems for the precise delivery of biomolecules.Specifically,we explore the multidimensional role of hydrogels in the sustained and localized release of antibodies,immunotherapeutic agents,and genes as next-generation platforms for localized cancer treatment.This review aims to critically evaluate the mechanisms and applications of these systems in order to assess their potential to transform medical interventions and advance patient care.
基金Noncommunicable Chronic Diseases-National Science and Technology Major Project,Grant/Award Number:2023ZD0502200National Natural Science Foundation of China,Grant/Award Number:82103010+2 种基金Cultivation Project of Medical Oncology Key Foundation of Cancer HospitalChinese Academy of Medical Sciences,Grant/Award Number:CICAMS-MOCP2022004Joint Innovative Fund of Beijing Natural Science Foundation and Changping District,Grant/Award Number:L234004。
文摘In recent years,multidisciplinary treatment strategies have profoundly improved drug responses and survival outcomes of breast cancer(BC)patients.However,there is an urgent need for novel therapies for BC patients who are heavily treated or develop resistance to conventional treatment regimens.Radionuclide therapy(RT)and targeted radionuclide therapy(TRT)have emerged as paradigm-shifting therapeutic approaches for BC,which enable functions of both imaging and localised treatment.They utilise radionuclides that can selectively bind to biomarkers overexpressing on BC cells,allowing precise delivery and localised tumour irradiation.Moreover,several types of radionuclides possess‘cross-fire’effects that result in the eradication of neighbouring tumour cells lacking the biomarker expression.In the current review,we summarise the potential biomarkers for the development of RT and TRT that can be employed in the treatment of BC,including receptor markers of ER,PR and HER2,together with other markers of Trop2,PD-1,EGFR,GRPR and PSMA.
文摘Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major cohort for stem cell-based therapies.However,the regenerative potential of stem cells significantly decreases with advanced age and deteriorating health status of the donor.Therefore,the efficacy of autologous stem cell therapy is significantly compromised in older patients.To overcome these limitations,alternative strategies have been used to restore the age-and disease-depleted function of stem cells.These methods aim to restore the therapeutic efficacy of aged stem cells for autologous use.This article explores the effect of donor age and health status on the regenerative potential of stem cells.It further highlights the limitations of stem cell-based therapy for autologous treatment in the elderly.A comprehensive insight into the potential strategies to address the“age”and“disease”compromised regenerative potential of autologous stem cells is also presented.The information provided here serves as a valuable resource for physicians and patients for optimization of stem cellbased autologous therapy for aged patients.
文摘Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,tau is not an easy target because it dynamically interacts with microtubules and other cellular components,which presents a challenge for tau-targeted drugs.New cellular models could aid the development of mechanism-based tau-targeted therapies.
文摘Therapy discontinuation in inflammatory bowel disease,particularly involving immunomodulators,biologics,and small molecules,remains a controversial and evolving topic.This letter reflects on developments following the publication by Meštrovićet al,emphasizing the complex balance between risks of relapse,antidrug antibody formation,and potential complications of long-term immunosuppression.Recent evidence underscores high relapse rates following withdrawal-especially of anti-tumor necrosis factor agents-and highlights the lack of robust data for newer biologics.Updated guidelines from European Crohn’s and Colitis Organization,British Society of Gastroenterology,and American College of Gastroenterology all support cautious and individualized approaches,with strict criteria and close follow-up,particularly in Crohn’s disease.For ulcerative colitis,therapeutic cycling remains insufficiently addressed.We proposed a flowchart to support clinical decision-making and stress the importance of shared decisionmaking in the era of personalized medicine since,despite new drug classes and evolving strategies,the therapeutic ceiling in inflammatory bowel disease has yet to be fully overcome.
基金supported by the National Natural Science Foundation of China (No. 82373809 to Y.L., No. 825B2116 to J.L., No. 82373805 to N.Z., No. 82204295 to W.M)the Shandong Excellent Youth Fund and Provincial Natural Science Foundation (ZR2022YQ76 to Y.L., ZR2022QH224 to W.M.)。
文摘Tumors pose a serious threat to human life and health. In recent years, gene therapy against tumors has garnered considerable attention. Small interfering RNAs(siRNAs), an important class of nucleic acid drugs, can silence the m RNAs of tumor-associated genes with high specificity through RNA interference(RNAi), inhibiting tumor-related signaling pathways or protein expression and thereby exerting anti-tumor effects. However, antitumor siRNA drugs are currently in the clinical research stage, and none of these drugs have been approved for marketing, mainly because of the challenges in terms of safety,efficacy and targeted delivery. Nano-delivery systems can enhance siRNA stability and improve siRNA pharmacokinetics and biodistribution, while increasing their uptake by target cells to achieve precise delivery and controlled release, thereby serving as a promising solution to overcome the challenges of siRNA drug application. This review summarizes the existing research on the nano-delivery systems currently available to help siRNAs achieve organ-targeted delivery and enhance the anti-tumor efficacy of siRNAs, discussing the characteristics of siRNA action and the unique advantages of different types of nanodelivery systems. The aim was to provide novel ideas for the design and optimization of siRNA-based drug delivery and the development of novel anti-tumor formulations to promote the clinical translation and application of siRNA drugs.
基金supported by the National Natural Science Foundation of China(Grant Nos.82472677,82404653,U25A20103,and 223B2704)the Natural Science Foundation of Shanghai(Grant No.23ZR1418900)the Natural Science Foundation of Chongqing(Grant No.CSTB2023NSCQ-MSX0367).
文摘KRAS is a critical proto-oncogene and molecular switch that is frequently mutated in human cancers.Oncogenic mutations,primarily at codons 12,13,and 61,lock KRAS into a GTPbound active state,thus resulting in constitutive signaling through downstream effectors such as RAF and phosphoinositide 3-kinase(PI3K)1.These alterations are highly prevalent in pancreatic cancer,colorectal cancer(CRC),and non-small cell lung cancer(NSCLC),and they drive tumor initiation,progression,and therapy resistance.
基金supported by the National Key R&D Program of China(No.2023YFB4705600)the National Natural Science Foundation of China(Nos.U23A20342,U20A20380,62273331,62127811,and 82373342)+4 种基金CAS Project for Young Scientists in Basic Research(No.YSBR-036)New Cornerstone Science Foundation through the XPLORER PRIZE,CAS/SAFEA International Partnership Program for Creative Research Teams,the Science and Technology Planning Project of Liaoning Province(No.2021JH1/10400049)Shengjing Hospital of China Medical University 345 Talent Project(No.1000801592)the Joint Project of Liaoning Province(No.2023JH2/101700202)“the Fundamental Research Funds for the Central Universities”,South-Central Minzu University(No.CZQ 25014).
文摘Diatoms,as natural sources of porous silica,have important potential for biomedical applications.Biohybrid microrobots also show promise for targeted delivery;however,research on converting diatoms into biohybrid microrobots and exploiting their intrinsic properties for cancer treatment remains limited.In this study,Thalassiosira weissflogii was transformed into biohybrid microrobots(Mag-Diatoms)while retaining its natural chlorophyll,thereby enabling Mag-Diatom-mediated photodynamic therapy(PDT)without additional drug modification.In this system,Mag-Diatoms act ed as microrobots,and their intrinsic chlorophyll serve d as a photosensitizer,exhibiting excellent biological safety.The autonomous closed-loop motion of the Mag-Diatoms was achieved using an artificial intelligence algorithm,which enabled controlled navigation along a preset trajectory.Mag-Diatoms also exhibited the ability to traverse narrow slits and target cancer cells within a cellular environment.The PDT effect was validated in vitro using human malignant glioblastoma(GBM)cell lines and primary cells derived from patients.The results revealed that the cell viability was closely related to the Mag-Diatom concentration,laser intensity,and irradiation time.Under combined Mag-Diatoms and laser treatment,viability decreased to 19.5%in primary cells and 3.6%in cell line models.Moreover,in vivo experiments using a mouse glioma model revealed that Mag-Diatom-mediated PDT effectively suppressed GBM progression.These findings highlight the potential of diatom-derived biohybrid microrobots,leveraging their natural properties,as a novel material and solution for PDT-based GBM therapy.
文摘Ischemic stroke therapy has long been dominated by strategies aimed at restoring cerebral blood flow. Yet, accumulating evidence suggests that neuronal survival and functional recovery depend not only on reperfusion, but also on the resolution of postischemic immune dysregulation. This study(Chen et al., Prog Biochem Biophys, 2026, 53(3): 697-710. DOI:10.3724/j.pibb.2025.0541) a dvances this emerging paradigm by proposing a therapeutic strategy that integrates lesion-specific delivery with active modulation of the inflammatory microenvironment.
基金the financial support from the Fujian Provincial Youth Top-Notch Talent Support Program,China.
文摘The clinical management of hypertrophic scars(HSs)remains challenging due to their complex etiology and heterogeneous morphology,underscoring the need for multitarget treatment strategies.In this study,we developed a nanocomposite system constructed through the metal-phenolic network-mediated self-assembly of molybdenum polyoxometalate({Mo 154})and epigallocatechin gallate(EGCG),followed by chitosan encapsulation,to generate chitosan-encapsulated{Mo 154}/EGCG(CME)nanoparticles.These nanoparticles were integrated into dissolvable microneedles(CME@MN)to enable transdermal administration.Under near-infrared laser irradiation,CME exhibited a three-pronged therapeutic effect:suppression of collagen overproduction and excessive extracellular matrix(ECM)deposition in human keloid fibroblasts,regulation of proliferation and migration in human umbilical vein endothelial cells,and reprogramming of macrophages toward a proinflammatory M1 phenotype.In vivo,CME@MN patches preferentially accumulated within scar tissue,where they normalized ECM organization,improved collagen fiber rearrangement,and attenuated fibroblast activity through photothermal-enhanced mechanisms while maintaining an excellent safety profile.The CME@MN system represents a potentially transformative approach to HS management by offering a unified platform that simultaneously targets the fibrotic,angiogenic,and inflammatory components of scar pathogenesis.
基金supported by National Natural Science Foundation of China(Grant 22407024)the Star-up Research Fund of Southeast University(RF1028624094)(X.W.)+7 种基金the China Postdoctoral Science Foundation(Grant 2025M772911)Natural Science Foundation of Jiangsu Province(Grants BK20251303)(X.L.)Postdoctoral Fellowship Program of CPSF(Grant GZC20251914)(X.L.)Jiangsu Funding Program for Excellent Postdoctoral Talent(Grant 2025ZB052)(X.L.)National Natural Science Foundation of China(Grant 22234002)(G.L.)National Key Research and Development Program of China(Grant 2023YFF0724100)(G.L.)Natural Science Foundation of Jiangsu Province(Grant BK20232007)(G.L.)Jiangsu ShuangChuang Team(Grant JSSCTD202409)(G.L.and X.W.).
文摘Targeted protein degradation(TPD)is an innovative strategy for selectively eliminating pathogenic proteins,enabling precise degradation of once-undruggable targets in cancer therapy.However,current TPD molecules are often limited by poor tumor targeting and the need for high doses.To overcome these limitations,assembly/disassembly-based TPD systems have been proposed to effectively degrade proteins of interest and enhance therapeutic efficacy.Herein,we summarize the recent advances in such TPD systems and categorize the strategies employed,including nanosphere morphology of assembled TPD systems,nanofiber morphology of assembled TPD systems,carrier-mediated TPD release systems,and stimulus-induced free TPD molecule formation nanosystems.Finally,we outline future directions and identify the remaining challenges in assembly/disassembly-based TPD systems.
