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
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
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
Malignant pleural effusion(MPE) is a serious disease caused by malignant tumors with high morbidity and mortality.Chemotherapy,immunotherapy,and antiangiogenic therapy are common treatments for MPE at present.However,...Malignant pleural effusion(MPE) is a serious disease caused by malignant tumors with high morbidity and mortality.Chemotherapy,immunotherapy,and antiangiogenic therapy are common treatments for MPE at present.However,traditional chemotherapeutic drugs have many side effects and can easily lead to drug resistance in patients.The complex tumor microenvironment(TME) of MPE directly reduces the antitumor efficacy of immunotherapy.Fortunately,drug delivery systems(DDSs) based on biomaterials have the ability to overcome some of the drawbacks of conventional treatments by improving drug stability,increasing the accuracy of tumor cell targeting,reducing toxic side effects,and remodeling TME,ultimately improving drug efficacy.Therefore,the purpose of this review is to provide an overview and discussion of the latest progress in biomaterial-based DDSs for the treatment of MPE.We discuss the application of biomaterials in the treatment of MPE from multiple perspectives,including chemotherapy,immunotherapy,combination therapy,and pleurodesis,where microspheres,cell membrane-derived microparticles(MPs),micelles,nanoparticles,and liposomes,are involved.The application of these biomaterials has been proven to have great potential in the treatment of MPE,providing a new idea for follow-up research.展开更多
BACKGROUND The liver represents a common site of distant metastasis in patients with esophageal cancer(EC).Conventional chemotherapy(CMT)presents limited efficacy for EC,and EC patients with liver metastases typically...BACKGROUND The liver represents a common site of distant metastasis in patients with esophageal cancer(EC).Conventional chemotherapy(CMT)presents limited efficacy for EC,and EC patients with liver metastases typically experience a poor prognosis,highlighting an urgent need to explore novel treatment approaches.This study evaluated the overall efficacy and safety of CMT vs CMT combined with immune checkpoint inhibitors(ICIs)in the treatment of EC patients with liver metastases.Furthermore,prognostic factors influencing outcomes in this patient population were identified.AIM To evaluate the efficacy and safety of first-line chemoimmunotherapy for EC patients with liver metastases and to analyze prognostic factors.METHODS This retrospective study included 126 EC patients with liver metastases at Zhejiang Cancer Hospital between 2014 and 2024.Patients receiving CMT were compared with those receiving CMT+ICI.Analyzed variables included clinicopathological features,treatment history,characteristics of metastasis,systemic and local treatments,overall survival(OS),and treatment-related adverse events(TRAEs).Prognostic factors were evaluated using univariate and multivariate Cox proportional-hazards regression models.Finally,efficacy outcomes and TRAE profiles were compared between the two groups.RESULTS A significant difference in median OS was identified between the two groups(10.8 months in the CMT group vs 20.8 months in the CMT+ICI group,P=0.004).The CMT+ICI group also demonstrated a significantly longer median progression-free survival of 11.7 months(P<0.001).Patients receiving combination therapy exhibited significantly improved systemic objective response rate and disease control rate.Multivariate analysis identified key factors significantly influencing OS in EC patients with liver metastases:Karnofsky Performance Status score≥70,receipt of local therapy for liver metastases,and the number of cycles of CMT and immunotherapy received.Furthermore,the incidence of TRAEs did not significantly differ between the CMT+ICI and CMT groups.CONCLUSION For EC patients with liver metastases,the combination of CMT and ICIs demonstrates significantly superior efficacy compared with CMT alone,while maintaining manageable TRAEs.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
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
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
Serbisütherapy(ST)is a distinctive external treatment modality within traditional Mongolian medicine(TMM),historically developed within a nomadic cultural framework.This study presents a comprehensive philologica...Serbisütherapy(ST)is a distinctive external treatment modality within traditional Mongolian medicine(TMM),historically developed within a nomadic cultural framework.This study presents a comprehensive philological and historical analysis of ST,tracing its evolution from early battlefield applications to contemporary clinical use.By critically examining classical Mongolian medical texts alongside modern case studies,we aim to systematize ST’s therapeutic methods,indications,and limitations,while exploring its mechanisms of action through both traditional theory and modern biomedical perspectives.ST has undergone significant transformation,shifting from whole-body cavity immersion in the 13th century to targeted,organ-specific applications in modern practice.Its four primary methods–Covering,Mounted,Organ Placement,and Suction–demonstrate efficacy in treating cold-natured diseases,musculoskeletal disorders,gynecological conditions,and certain emergencies.ST embodies the core principles of TMM,particularly the balance of the“Three Roots”and the correction of cold-induced pathologies through heat.Despite challenges related to standardization,cultural translation,and regulatory acceptance,ST holds translational potential for integrative medicine.Future research should prioritize mechanistic validation,clinical standardization,and the development of biocompatible thermal technologies to bridge traditional practice with modern healthcare systems.展开更多
Pancreatic ductal adenocarcinoma(PDAC)remains one of the most lethal malignancies,characterized by a highly immunosuppressive tumor microenvironment(TME),dense stromal architecture,and limited response to conventional...Pancreatic ductal adenocarcinoma(PDAC)remains one of the most lethal malignancies,characterized by a highly immunosuppressive tumor microenvironment(TME),dense stromal architecture,and limited response to conventional therapies.This review comprehensively examines the emerging role of chimeric antigen receptor(CAR)-engineered immune cells,including chimeric antigen receptor-T(CAR-T),CAR-macrophages(CAR-M),and CAR-natural killer(CAR-NK)cells,as innovative immunotherapeutic strategies for PDAC.We delve into the mechanistic foundations of these platforms,highlighting their unique abilities to target tumor-associated antigens,overcome stromal barriers,and remodel the immunosuppressive TME.Recent preclinical and clinical advances demonstrate promising antitumor activity,particularly with targets such as mesothelin,claudin18.2,and human epidermal growth factor 2(HER2),though challenges related to antigen heterogeneity,TME suppression,and cell persistence remain.We further discuss synergistic approaches involving genetic engineering,microenvironment modulation,and combination therapies aimed at enhancing efficacy.Finally,we offer perspectives on the future direction of CARbased therapies,including the development of next-generation constructs,allogeneic“off-the-shelf”products,and personalized combination regimens,underscoring their potential in pancreatic cancer.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
Introduction:Chemotherapy-induced gastrointestinal symptom clusters in breast cancer impair quality of life and treatment adherence,yet lack effective interventions.While acupuncture mitigates isolated chemotherapy-in...Introduction:Chemotherapy-induced gastrointestinal symptom clusters in breast cancer impair quality of life and treatment adherence,yet lack effective interventions.While acupuncture mitigates isolated chemotherapy-induced symptoms,its mechanisms for multi-symptom clusters remain unclear.This study evaluates electroacupuncture's efficacy and explores its biological mechanisms in managing these clusters.Methods:This prospective,multicenter,block-randomized,double-blind,sham-controlled trial will enroll 388 patients with breast cancer undergoing neoadjuvant/adjuvant chemotherapy,to be randomly assigned(1:1)to electroacupuncture or sham electro-acupuncture groups.Both groups will receive the standard quadruple antiemetic regimen combined with electroacupuncture or sham intervention.The primary endpoint is the incidence of chemotherapy-induced gastrointestinal symptom clusters within 120 h after chemotherapy.Secondary endpoints include improvement in gastrointestinal symptom clusters post-first chemotherapy cycle,nausea-free rates during acute and delayed phases,vomiting-free rates during overall,acute,and delayed phases,complete response rate,complete protection rate,and quality of life.Adverse events will be documented throughout the study.Discussion:This study will assess the efficacy and safety of electroacupuncture in alleviating chemotherapy-induced gastro-intestinal symptom clusters in patients with breast cancer.By integrating multi-omics analyses,we aim to elucidate the biological mechanisms underlying its therapeutic effects.The findings may offer a robust clinical foundation for optimizing symptom cluster management in cancer care.Trial Registration:Clinical Trials ID:NCT06952920.Date of registration:April 16,2025.Prospectively registered.URL of Trial Registry Record:https://clinicaltrials.gov/study/NCT06952920cond=NCT06952920&rank=1.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
A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an or...A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.展开更多
Synergistic therapy using multiple modalities is a highly promising therapeutic strategy.Near-infrared-Ⅱ(NIR-Ⅱ)fluorescence imaging,with its deep penetration and high fidelity,has frequently been employed in the lit...Synergistic therapy using multiple modalities is a highly promising therapeutic strategy.Near-infrared-Ⅱ(NIR-Ⅱ)fluorescence imaging,with its deep penetration and high fidelity,has frequently been employed in the literature to guide and assist treatment.Herein,we report the development of a NIR-Ⅱfluorescence imaging guided multi-therapy platform PDI-DS NPs,which integrates a novel activatable phototheranostic agent PDI-DBU,a H_(2)S donor DPS and an amphiphilic polymer DSPE-m PEG2000.In order to maximize redshift of absorption and emission of PDI derivatives,we introduced an electron donating group DBU on PDI to obtain PDI-DBU.PDI-DBU exhibits a distinct absorption band at 700-900 nm and demonstrates excellent NIR-Ⅱfluorescence emission/imaging properties and good photothermal effects under 808 nm laser irradiation.More importantly,under 808 nm laser irradiation,PDI-DBU could be oxidized,and the photodynamic effect of the material could be subsequently activated under 530 nm laser irradiation,achieving the combination of photothermal and activatable photodynamic dual modality treatment.The H_(2)S donor DPS,when triggered by the abundant glutathione(GSH)within the tumor microenvironment(TME),is capable of generating H_(2)S.On one hand,H_(2)S can inhibit tumor growth by disrupting mitochondrial function,on the other hand,it can also repress the expression of heat shock protein 90(HSP90),thereby reversing tumor cell resistance mechanism against photothermal therapy.The utilization of PDI-DS NPs combined with DPS for efficient tumor ablation has been successfully demonstrated both in vitro and in vivo.This synergistic therapeutic platform thus offers a promising strategy in the field of NIR-Ⅱfluorescence imaging guided tumor therapy.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
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
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
This study aimed to develop a multimodal imaging histological model based on computed tomography(CT)images and carcinoembryonic antigen(CEA)values to predict the efficacy of preoperative neoadjuvant therapy in rectal ...This study aimed to develop a multimodal imaging histological model based on computed tomography(CT)images and carcinoembryonic antigen(CEA)values to predict the efficacy of preoperative neoadjuvant therapy in rectal cancer patients.Data were obtained from the Database of Colorectal Cancer of West China Hospital of Sichuan University.A total of 155 patients were enrolled and categorized into good and poor response groups based on pathological evaluation using the tumor regression grade system.Radiomics features were extracted from CT images using PyRadiomics software,and CEA data were collected and processed.Three types of models—a clinical model,a pure radiomics model,and an integrated model—were constructed using logistic regression,support vector machine,random forest(RF),and XGBoost algorithms.The results showed that the integrated model,particularly the RF and XGBoost models,demonstrated the best predictive performance.The RF model achieved an area under the curve(AUC)value of 0.96 in the test set,with accuracy,sensitivity,and specificity of 0.88,0.50,and 1.00,respectively.The XGBoost model had the highest AUC value of 0.97 in the test set,with accuracy,sensitivity,and specificity of 0.91,0.70,and 0.97,respectively.This model can be integrated into existing clinical practice to provide clinicians with additional insights for guiding treatment decisions.Future studies should recruit a larger and more diverse patient population to validate and refine the model,and prospective validation is needed to assess its real-world applicability.展开更多
The development of highly effective therapeutics is a priority in addressing the escalating threat that cancer poses to human health.Cyclodextrins(CDs) with exceptional biocompatibility and devisable structural hierar...The development of highly effective therapeutics is a priority in addressing the escalating threat that cancer poses to human health.Cyclodextrins(CDs) with exceptional biocompatibility and devisable structural hierarchy are emerging as versatile building blocks for engineered drug delivery systems,showing a promising prospect in cancer therapy.CDs enable precise synthesis of functionalized polymers with tailored architectures,endowing their excellent stability and large surface area to prolong drug circulation,enhance solubility,and increase targeting efficiency.Recently,CD-based nanotherapeutics has shown transformative potential in chemotherapy,phototherapy,immunotherapy,gene therapy and other codelivery systems of combination therapy.This review will introduce the types of CD-based nanotherapeutics,systematically summarize their design methods and anticancer application,and further discuss the prospects and challenges,providing a roadmap for advancing CD nanotechnology toward cancer therapeutics.展开更多
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.
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.
基金financial support from the Noncommunicable Chronic Diseases-National Science and Technology Major Project (Nos.2024ZD0522800,2024ZD0522803)the National Natural Science Foundation of China (Nos.U21A20417,31930067,31800797)+2 种基金the Natural Science Foundation of Sichuan Province (No.2024NSFSC0046)the Sichuan Science and Technology Program (No.2022YFS0333)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University (No.ZYGD24003)。
文摘Malignant pleural effusion(MPE) is a serious disease caused by malignant tumors with high morbidity and mortality.Chemotherapy,immunotherapy,and antiangiogenic therapy are common treatments for MPE at present.However,traditional chemotherapeutic drugs have many side effects and can easily lead to drug resistance in patients.The complex tumor microenvironment(TME) of MPE directly reduces the antitumor efficacy of immunotherapy.Fortunately,drug delivery systems(DDSs) based on biomaterials have the ability to overcome some of the drawbacks of conventional treatments by improving drug stability,increasing the accuracy of tumor cell targeting,reducing toxic side effects,and remodeling TME,ultimately improving drug efficacy.Therefore,the purpose of this review is to provide an overview and discussion of the latest progress in biomaterial-based DDSs for the treatment of MPE.We discuss the application of biomaterials in the treatment of MPE from multiple perspectives,including chemotherapy,immunotherapy,combination therapy,and pleurodesis,where microspheres,cell membrane-derived microparticles(MPs),micelles,nanoparticles,and liposomes,are involved.The application of these biomaterials has been proven to have great potential in the treatment of MPE,providing a new idea for follow-up research.
基金Supported by National Natural Science Foundation of China,No.82303672Zhejiang Provincial Health Commission and Zhejiang Provincial Administration of Traditional Chinese Medicine through the Targeted Project for Medical and Health Research,No.2025ZL017and China Primary Health Care Foundation,No.ZLMY20240311001ZJ.
文摘BACKGROUND The liver represents a common site of distant metastasis in patients with esophageal cancer(EC).Conventional chemotherapy(CMT)presents limited efficacy for EC,and EC patients with liver metastases typically experience a poor prognosis,highlighting an urgent need to explore novel treatment approaches.This study evaluated the overall efficacy and safety of CMT vs CMT combined with immune checkpoint inhibitors(ICIs)in the treatment of EC patients with liver metastases.Furthermore,prognostic factors influencing outcomes in this patient population were identified.AIM To evaluate the efficacy and safety of first-line chemoimmunotherapy for EC patients with liver metastases and to analyze prognostic factors.METHODS This retrospective study included 126 EC patients with liver metastases at Zhejiang Cancer Hospital between 2014 and 2024.Patients receiving CMT were compared with those receiving CMT+ICI.Analyzed variables included clinicopathological features,treatment history,characteristics of metastasis,systemic and local treatments,overall survival(OS),and treatment-related adverse events(TRAEs).Prognostic factors were evaluated using univariate and multivariate Cox proportional-hazards regression models.Finally,efficacy outcomes and TRAE profiles were compared between the two groups.RESULTS A significant difference in median OS was identified between the two groups(10.8 months in the CMT group vs 20.8 months in the CMT+ICI group,P=0.004).The CMT+ICI group also demonstrated a significantly longer median progression-free survival of 11.7 months(P<0.001).Patients receiving combination therapy exhibited significantly improved systemic objective response rate and disease control rate.Multivariate analysis identified key factors significantly influencing OS in EC patients with liver metastases:Karnofsky Performance Status score≥70,receipt of local therapy for liver metastases,and the number of cycles of CMT and immunotherapy received.Furthermore,the incidence of TRAEs did not significantly differ between the CMT+ICI and CMT groups.CONCLUSION For EC patients with liver metastases,the combination of CMT and ICIs demonstrates significantly superior efficacy compared with CMT alone,while maintaining manageable TRAEs.
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.
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.
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 China Ethnic Medicine Association Research Grant(No.2023MY055-81)Science and Technology Program of the Joint Fund of Scientific Research for the Public Hospitals of Inner Mongolia Academy of Medical Sciences(2023GLLHD177,2023GLLH0174)Inner Mongolia Autonomous Region Regional Medical Center for Specialized Care(2025).
文摘Serbisütherapy(ST)is a distinctive external treatment modality within traditional Mongolian medicine(TMM),historically developed within a nomadic cultural framework.This study presents a comprehensive philological and historical analysis of ST,tracing its evolution from early battlefield applications to contemporary clinical use.By critically examining classical Mongolian medical texts alongside modern case studies,we aim to systematize ST’s therapeutic methods,indications,and limitations,while exploring its mechanisms of action through both traditional theory and modern biomedical perspectives.ST has undergone significant transformation,shifting from whole-body cavity immersion in the 13th century to targeted,organ-specific applications in modern practice.Its four primary methods–Covering,Mounted,Organ Placement,and Suction–demonstrate efficacy in treating cold-natured diseases,musculoskeletal disorders,gynecological conditions,and certain emergencies.ST embodies the core principles of TMM,particularly the balance of the“Three Roots”and the correction of cold-induced pathologies through heat.Despite challenges related to standardization,cultural translation,and regulatory acceptance,ST holds translational potential for integrative medicine.Future research should prioritize mechanistic validation,clinical standardization,and the development of biocompatible thermal technologies to bridge traditional practice with modern healthcare systems.
文摘Pancreatic ductal adenocarcinoma(PDAC)remains one of the most lethal malignancies,characterized by a highly immunosuppressive tumor microenvironment(TME),dense stromal architecture,and limited response to conventional therapies.This review comprehensively examines the emerging role of chimeric antigen receptor(CAR)-engineered immune cells,including chimeric antigen receptor-T(CAR-T),CAR-macrophages(CAR-M),and CAR-natural killer(CAR-NK)cells,as innovative immunotherapeutic strategies for PDAC.We delve into the mechanistic foundations of these platforms,highlighting their unique abilities to target tumor-associated antigens,overcome stromal barriers,and remodel the immunosuppressive TME.Recent preclinical and clinical advances demonstrate promising antitumor activity,particularly with targets such as mesothelin,claudin18.2,and human epidermal growth factor 2(HER2),though challenges related to antigen heterogeneity,TME suppression,and cell persistence remain.We further discuss synergistic approaches involving genetic engineering,microenvironment modulation,and combination therapies aimed at enhancing efficacy.Finally,we offer perspectives on the future direction of CARbased therapies,including the development of next-generation constructs,allogeneic“off-the-shelf”products,and personalized combination regimens,underscoring their potential in pancreatic cancer.
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.
基金Noncommunicable Chronic Diseases-National Science and Technology Major Project,Grant/Award Numbers:2024ZD0521400,2024ZD0521404Affiliated Hospital of Qinghai University。
文摘Introduction:Chemotherapy-induced gastrointestinal symptom clusters in breast cancer impair quality of life and treatment adherence,yet lack effective interventions.While acupuncture mitigates isolated chemotherapy-induced symptoms,its mechanisms for multi-symptom clusters remain unclear.This study evaluates electroacupuncture's efficacy and explores its biological mechanisms in managing these clusters.Methods:This prospective,multicenter,block-randomized,double-blind,sham-controlled trial will enroll 388 patients with breast cancer undergoing neoadjuvant/adjuvant chemotherapy,to be randomly assigned(1:1)to electroacupuncture or sham electro-acupuncture groups.Both groups will receive the standard quadruple antiemetic regimen combined with electroacupuncture or sham intervention.The primary endpoint is the incidence of chemotherapy-induced gastrointestinal symptom clusters within 120 h after chemotherapy.Secondary endpoints include improvement in gastrointestinal symptom clusters post-first chemotherapy cycle,nausea-free rates during acute and delayed phases,vomiting-free rates during overall,acute,and delayed phases,complete response rate,complete protection rate,and quality of life.Adverse events will be documented throughout the study.Discussion:This study will assess the efficacy and safety of electroacupuncture in alleviating chemotherapy-induced gastro-intestinal symptom clusters in patients with breast cancer.By integrating multi-omics analyses,we aim to elucidate the biological mechanisms underlying its therapeutic effects.The findings may offer a robust clinical foundation for optimizing symptom cluster management in cancer care.Trial Registration:Clinical Trials ID:NCT06952920.Date of registration:April 16,2025.Prospectively registered.URL of Trial Registry Record:https://clinicaltrials.gov/study/NCT06952920cond=NCT06952920&rank=1.
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.
文摘A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.
基金supported by the National Natural Science Foundation of China(No.22274148)the Science and Technology Development Foundation of Jilin Province(Nos.20220204098YY,20230402045GH,20230402018GH,YDZJ202201ZYTS359,YDZJ202201ZYTS351,20240404070ZP,SKL202302030)the Jilin Province Development and Reform Commission’s Innovation Capacity Building Program(No.2023C041-8)。
文摘Synergistic therapy using multiple modalities is a highly promising therapeutic strategy.Near-infrared-Ⅱ(NIR-Ⅱ)fluorescence imaging,with its deep penetration and high fidelity,has frequently been employed in the literature to guide and assist treatment.Herein,we report the development of a NIR-Ⅱfluorescence imaging guided multi-therapy platform PDI-DS NPs,which integrates a novel activatable phototheranostic agent PDI-DBU,a H_(2)S donor DPS and an amphiphilic polymer DSPE-m PEG2000.In order to maximize redshift of absorption and emission of PDI derivatives,we introduced an electron donating group DBU on PDI to obtain PDI-DBU.PDI-DBU exhibits a distinct absorption band at 700-900 nm and demonstrates excellent NIR-Ⅱfluorescence emission/imaging properties and good photothermal effects under 808 nm laser irradiation.More importantly,under 808 nm laser irradiation,PDI-DBU could be oxidized,and the photodynamic effect of the material could be subsequently activated under 530 nm laser irradiation,achieving the combination of photothermal and activatable photodynamic dual modality treatment.The H_(2)S donor DPS,when triggered by the abundant glutathione(GSH)within the tumor microenvironment(TME),is capable of generating H_(2)S.On one hand,H_(2)S can inhibit tumor growth by disrupting mitochondrial function,on the other hand,it can also repress the expression of heat shock protein 90(HSP90),thereby reversing tumor cell resistance mechanism against photothermal therapy.The utilization of PDI-DS NPs combined with DPS for efficient tumor ablation has been successfully demonstrated both in vitro and in vivo.This synergistic therapeutic platform thus offers a promising strategy in the field of NIR-Ⅱfluorescence imaging guided tumor therapy.
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.
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.
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 the 1-3-5 projects for artificial intelligence(Grant No.:ZYAI24067)West China Hospital,Sichuan University and the medical research project(Grant No.:S2024045),Sichuan Medical Association.
文摘This study aimed to develop a multimodal imaging histological model based on computed tomography(CT)images and carcinoembryonic antigen(CEA)values to predict the efficacy of preoperative neoadjuvant therapy in rectal cancer patients.Data were obtained from the Database of Colorectal Cancer of West China Hospital of Sichuan University.A total of 155 patients were enrolled and categorized into good and poor response groups based on pathological evaluation using the tumor regression grade system.Radiomics features were extracted from CT images using PyRadiomics software,and CEA data were collected and processed.Three types of models—a clinical model,a pure radiomics model,and an integrated model—were constructed using logistic regression,support vector machine,random forest(RF),and XGBoost algorithms.The results showed that the integrated model,particularly the RF and XGBoost models,demonstrated the best predictive performance.The RF model achieved an area under the curve(AUC)value of 0.96 in the test set,with accuracy,sensitivity,and specificity of 0.88,0.50,and 1.00,respectively.The XGBoost model had the highest AUC value of 0.97 in the test set,with accuracy,sensitivity,and specificity of 0.91,0.70,and 0.97,respectively.This model can be integrated into existing clinical practice to provide clinicians with additional insights for guiding treatment decisions.Future studies should recruit a larger and more diverse patient population to validate and refine the model,and prospective validation is needed to assess its real-world applicability.
基金financially supported by National Natural Science Foundation of China (No.3240117,X.S)Sichuan Science and Technology Program (No.2024YFFK0345,Z.X)+3 种基金Natural Science Foundation of Chongqing (No.CSTB2024NSCQ-MSX0046,F.R)Startup Fund of Chongqing Normal University (No.23XLB036,F.R)National College Student Innovation and Entrepreneurship Program of Southwest University (No.202410635109,Y.Z)Guangdong High-level Hospital Construction Fund。
文摘The development of highly effective therapeutics is a priority in addressing the escalating threat that cancer poses to human health.Cyclodextrins(CDs) with exceptional biocompatibility and devisable structural hierarchy are emerging as versatile building blocks for engineered drug delivery systems,showing a promising prospect in cancer therapy.CDs enable precise synthesis of functionalized polymers with tailored architectures,endowing their excellent stability and large surface area to prolong drug circulation,enhance solubility,and increase targeting efficiency.Recently,CD-based nanotherapeutics has shown transformative potential in chemotherapy,phototherapy,immunotherapy,gene therapy and other codelivery systems of combination therapy.This review will introduce the types of CD-based nanotherapeutics,systematically summarize their design methods and anticancer application,and further discuss the prospects and challenges,providing a roadmap for advancing CD nanotechnology toward cancer therapeutics.