In this study,we developed a novel bilayered scaffold consisting of a bottom layer composed of the Decellularized Bovine Pericardium(DP)coated with Polyaniline Nanoparticles(PANINPs)and a top layer made of an electros...In this study,we developed a novel bilayered scaffold consisting of a bottom layer composed of the Decellularized Bovine Pericardium(DP)coated with Polyaniline Nanoparticles(PANINPs)and a top layer made of an electrospun Poly(lactic-co-glycolic acid)/Gelatin(PLGA/Gel)membrane incorporated with Vascular Endothelial Growth Fac-tor(VEGF)and hawthorn extract.Functionally,the DP supplies native Extracellular Matrix(ECM)components and mechanical support,while PANINPs provide conductivity.The electrospun PLGA/Gel layer mimics fibrous ECM.It incorporates bioactives,with VEGF promoting pro-angiogenic stimulation and hawthorn extract enhanc-ing anticoagulant activity,as well as increasing surface hydrophilicity.The tissue adhesive ensures the interfacial integrity between the two layers.Decellularization efficiency was confirmed histologically using 4',6-diamidino-2-phenylindole(DAPI)and Hematoxylin-Eosin(H&E)staining.The DP exhibited a DNA content of 115.9±47.8 ng/mg DNA,compared to 982.88±395.42 ng/mg in Native Pericardium(NP).The PANINPs had an average par-ticle size of 104.94±13.7 nm.The conductivity of PANINPs-coated decellularized pericardium was measured to be 9.093±8.6×10-4 S/cm using the four-point probe method.PLGA/Gel membranes containing hawthorn extract(1%,5%,10%,and 15%w/v)and VEGF(0.1μg/mL,0.5μg/mL,and 1μg/mL)were fabricated by electrospinning,result-ing in fiber diameters between 850 and 1200 nm and pore sizes between 14 and 20μm.The anticoagulant efficiency of the membranes containing hawthorn extract reached 430 s in the Activated Partial Thromboplastin Time Assay(aPTT).Mechanical testing revealed a tensile strength of 22.70±6.33 MPa,an elongation of 53.58±10.63%,and Young's modulus of 0.67±0.10 MPa.The scaffold also exhibited over 91%cell viability and excellent cardiomyo-cyte adhesion.The hemolysis ratio was determined to be 0.421±0.191%,which confirms its blood compatibility.Our results indicate that the proposed bilayered scaffold can be a promising candidate for cardiac patch applications.展开更多
Cancer is the second leading cause of death globally.Its treatment remains a major challenge due to the disease's complexity,heterogeneity,and adaptive nature.Among the array of available treatments,targeted thera...Cancer is the second leading cause of death globally.Its treatment remains a major challenge due to the disease's complexity,heterogeneity,and adaptive nature.Among the array of available treatments,targeted therapy emerges as a paramount approach to address this substantial unmet clinical need,owing to its precise tumor targeting capabilities and potential for mitigating tumor progression risks.Drug conjugates are in high demand for targeted therapy due to their unique ligand specificity and potent cytotoxicity,thereby significantly enhancing therapeutic efficacy and reducing the incidence of adverse effects.Therefore,as a burgeoning field in biomedical research,it is timely to outline the latest advances in drug conjugates-driven cancer treatment.Herein,we aim to present the emerging breakthroughs in this exciting field at the intersection of target ligands,linkers,payloads,and cancer treatments.This review focuses on several drug conjugates-related strategies,including antibody-drug conjugates(ADCs),peptide-drug conjugates(PDCs),small molecule-drug conjugates(SMDCs),aptamer-drug conjugates(ApDCs)and radionuclide-drug conjugates(RDCs).Finally,we discuss the fundamentals behind drug conjugate-based anticancer therapeutics,along with their inherent advantages and associated challenges,as well as recent research advances.展开更多
Modern medicine is expanding the possibilities of receiving "personalized" diagnosis and therapies,providing minimal invasiveness,technological solutions based on non-ionizing radiation,early detection of pa...Modern medicine is expanding the possibilities of receiving "personalized" diagnosis and therapies,providing minimal invasiveness,technological solutions based on non-ionizing radiation,early detection of pathologies with the main objectives of being operator independent and with low cost to society.Our research activities aim to strongly contribute to these trends by improving the capabilities of current diagnostic imaging systems,which are of key importance in possibly providing both optimal diagnosis and therapies to patients.In medical diagnostics,cellular imaging aims to develop new methods and technologies for the detection of specific metabolic processes in living organisms,in order to accurately identify and discriminate normal from pathological tissues.In fact,most diseases have a "molecular basis" that detected through these new diagnostic methodologies can provide enormous benefits to medicine.Nowadays,this possibility is mainly related to the use of Positron Emission Tomography,with an exposure to ionizing radiation for patients and operators and with extremely high medical diagnosticscosts.The future possible development of non-ionizing cellular imaging based on techniques such as Nuclear Magnetic Resonance or Ultrasound,would represent an important step towards modern and personalized therapies.During the last decade,the field of nanotechnology has made important progress and a wide range of organic and inorganic nanomaterials are now available with an incredible number of further combinations with other compounds for cellular targeting.The availability of these new advanced nanosystems allows new scenarios in diagnostic methodologies which are potentially capable of providing morphological and functional information together with metabolic and cellular indications.展开更多
Since the recognition of disease molecular basis,it has become clear that the keystone moments of medical practice,namely early diagnosis,appropriate therapeutic treatment and patient follow-up,must be approached at a...Since the recognition of disease molecular basis,it has become clear that the keystone moments of medical practice,namely early diagnosis,appropriate therapeutic treatment and patient follow-up,must be approached at a molecular level.These objectives will be in the near future more effectively achievable thanks to the impressive developments in nanotechnologies and their applications to the biomedical field,starting-up the nanomedicine era.The continuous advances in the development of biocompatible smart nanomaterials,in particular,will be crucial in several aspects of medicine.In fact,the possibility of manufacturing nanoparticle contrast agents that can be selectively targeted to specific pathological cells has extended molecular im-aging applications to non-ionizing techniques and,at the same time,has made reachable the perspective of combining highly accurate diagnoses and personalized therapies in a single theranostic intervention.Main developing applications of nanosized theranostic agents include targeted molecular imaging,controlled drug release,therapeutic monitoring,guidance of radiationbased treatments and surgical interventions.Here we will review the most recent findings in nanoparticles contrast agents and their applications in the field of cancer molecular imaging employing non-ionizing techniques and disease-specific contrast agents,with special focus on recent findings on those nanomaterials particularly promising for ultrasound molecular imaging and simultaneous treatment of cancer.展开更多
Recombinant technology-based vaccines have emerged as a highly effective way to prevent a wide range of illnesses.The technology improved vaccine manufacturing,rendering it more efficient and economical.These vaccines...Recombinant technology-based vaccines have emerged as a highly effective way to prevent a wide range of illnesses.The technology improved vaccine manufacturing,rendering it more efficient and economical.These vaccines have multiple advantages compared to conventional vaccines.The pandemic has heightened awareness of the advantages of these vaccine technologies;trust and acceptance of these vaccines are steadily growing globally.This work offers an overview of the prospects and advantages associated with recombinant vaccines.Additionally,it discusses some of the challenges likely to arise in the future.Their ability to target diverse pathogen classes underscores their contributions to preventing previously untreatable diseases(especially vector-borne and emerging diseases)and hurdles faced throughout the vaccine development process,especially in enhancing the effectiveness of these vaccines.Moreover,their compatibility with emerging vaccination platforms of the future like virus-like particles and CRISPR/Cas9 for the production of next-generation vaccines may offer many prospects.This review also reviewed the hurdles faced throughout the vaccine development process,especially in enhancing the effectiveness of these vaccines against vector-borne diseases,emerging diseases,and untreatable diseases with high mortality rates like AIDS as well as cancer.展开更多
Photodynamic therapy(PDT)has been extensively investigated as an alternative cancer treatment;however,its efficacy is limited by the low oxygen content and excess glutathione(GSH)in tumor tissues.With the emergence of...Photodynamic therapy(PDT)has been extensively investigated as an alternative cancer treatment;however,its efficacy is limited by the low oxygen content and excess glutathione(GSH)in tumor tissues.With the emergence of ferroptosis,which also impacts redox homeostasis,a combined PDT-ferroptosis approach holds promise for amplifying the efficacy of both treatments.However,concerns persist regarding biocompatibility and tumor-specific release.Here,we report a self-motivated co-nanoassembly for combined PDT and ferroptosis-driven tumor therapy.We first modify linoleic acid with protoporphyrin Ⅸ to form a lipidic derivative(denoted as PLA)and develop a light-boosted carrier-free nanoplatform(PLA@R NPs)by co-assembling the ferroptosis inducer RAS-selective lethal 3(RSL3)and PLA.Upon light irradiation,reactive oxygen species produced by PDT trigger linoleic acid peroxidation,leading to the destruction of the nanoparticles and the release of RSL3.The rapid release of RSL3 enhances PDT sensitivity by depleting GSH and utilizing the Fenton reaction to supplement oxygen.Additionally,PDT accelerates lipid peroxidation,further inducing ferroptosis.This self-motivated effect increases oxidative stress in tumor tissues,as confirmed by a tumor-on-a-chip model.Moreover,the in vivo therapeutic effect with the PLA@R NPs is significant,demonstrating the promising potential of combining PDT and ferroptosis using a light-boosted and self-motivated nanoplatform.展开更多
In the United States,1 in 10 infants are born preterm.The majority of neonatal deaths and nearly a third of infant deaths are linked to preterm birth.Preterm birth is initiated when the quiescent state of the uterus e...In the United States,1 in 10 infants are born preterm.The majority of neonatal deaths and nearly a third of infant deaths are linked to preterm birth.Preterm birth is initiated when the quiescent state of the uterus ends prematurely,leading to contractions and parturition beginning as early as 32 weeks,though the origins are not well understood.To enable research and discovery of therapeutics with potential to better address preterm birth,the capability to study isolated cell processes of pregnant uterine tissue in vitro is needed.Our development of an in vitro model of the myometrium utilizing human uterine smooth muscle cells(uSMCs)responsible for contractions provides a methodology to examine cellular mechanisms of late-stage pregnancy potentially involved in preterm birth.We discuss culture of uSMCs on a flexible polydimethylsiloxane(PDMS)substrate functionalized with cationic poly-L-lysine(PLL),followed by extracellular matrix(ECM)protein coating.Previous work exploring uSMC behavior on PDMS substrates have utilized collagen-I coatings,however,we demonstrated the first exploration of human uSMC response to strain on fibronectin-coated flexible membranes,importantly reflecting the significant increase of fibronectin content found in the myometrial ECM during late-stage pregnancy.Using the model we developed,we conducted proof-of-concept studies to investigate the impact of substrate strain on uSMC cell morphology and gene expression.It was found that PLL and varied ECM protein coatings(collagen I,collagen III,and fibronectin)altered cell nuclei morphology and density on PDMS substrates.Additionally,varied strain rates applied to uSMC substrates significantly impacted uSMC gene expression of IL-6,a cytokine associated with instances of preterm labor.These results suggest that both surface and mechanical properties of in vitro systems impact primary human uSMC phenotype and offer uSMC culture methodologies that can be utilized to further the understanding of cellular pathways involved in the uterus under mechanical load.展开更多
文摘In this study,we developed a novel bilayered scaffold consisting of a bottom layer composed of the Decellularized Bovine Pericardium(DP)coated with Polyaniline Nanoparticles(PANINPs)and a top layer made of an electrospun Poly(lactic-co-glycolic acid)/Gelatin(PLGA/Gel)membrane incorporated with Vascular Endothelial Growth Fac-tor(VEGF)and hawthorn extract.Functionally,the DP supplies native Extracellular Matrix(ECM)components and mechanical support,while PANINPs provide conductivity.The electrospun PLGA/Gel layer mimics fibrous ECM.It incorporates bioactives,with VEGF promoting pro-angiogenic stimulation and hawthorn extract enhanc-ing anticoagulant activity,as well as increasing surface hydrophilicity.The tissue adhesive ensures the interfacial integrity between the two layers.Decellularization efficiency was confirmed histologically using 4',6-diamidino-2-phenylindole(DAPI)and Hematoxylin-Eosin(H&E)staining.The DP exhibited a DNA content of 115.9±47.8 ng/mg DNA,compared to 982.88±395.42 ng/mg in Native Pericardium(NP).The PANINPs had an average par-ticle size of 104.94±13.7 nm.The conductivity of PANINPs-coated decellularized pericardium was measured to be 9.093±8.6×10-4 S/cm using the four-point probe method.PLGA/Gel membranes containing hawthorn extract(1%,5%,10%,and 15%w/v)and VEGF(0.1μg/mL,0.5μg/mL,and 1μg/mL)were fabricated by electrospinning,result-ing in fiber diameters between 850 and 1200 nm and pore sizes between 14 and 20μm.The anticoagulant efficiency of the membranes containing hawthorn extract reached 430 s in the Activated Partial Thromboplastin Time Assay(aPTT).Mechanical testing revealed a tensile strength of 22.70±6.33 MPa,an elongation of 53.58±10.63%,and Young's modulus of 0.67±0.10 MPa.The scaffold also exhibited over 91%cell viability and excellent cardiomyo-cyte adhesion.The hemolysis ratio was determined to be 0.421±0.191%,which confirms its blood compatibility.Our results indicate that the proposed bilayered scaffold can be a promising candidate for cardiac patch applications.
基金the Project of China-Japan Joint International Laboratory of Advanced Drug Delivery System Research and Translation of Liaoning Province(No.2024JH2/102100007)the open fund of National Key Laboratory of Advanced DrugFormulations for Overcoming Delivery Barriers(No.2024-KFB-003)+1 种基金the National Natural Science Foundation of China(No.82104109)Scientific Research Project of Liaoning Department of Education(No.LJ212410163045).
文摘Cancer is the second leading cause of death globally.Its treatment remains a major challenge due to the disease's complexity,heterogeneity,and adaptive nature.Among the array of available treatments,targeted therapy emerges as a paramount approach to address this substantial unmet clinical need,owing to its precise tumor targeting capabilities and potential for mitigating tumor progression risks.Drug conjugates are in high demand for targeted therapy due to their unique ligand specificity and potent cytotoxicity,thereby significantly enhancing therapeutic efficacy and reducing the incidence of adverse effects.Therefore,as a burgeoning field in biomedical research,it is timely to outline the latest advances in drug conjugates-driven cancer treatment.Herein,we aim to present the emerging breakthroughs in this exciting field at the intersection of target ligands,linkers,payloads,and cancer treatments.This review focuses on several drug conjugates-related strategies,including antibody-drug conjugates(ADCs),peptide-drug conjugates(PDCs),small molecule-drug conjugates(SMDCs),aptamer-drug conjugates(ApDCs)and radionuclide-drug conjugates(RDCs).Finally,we discuss the fundamentals behind drug conjugate-based anticancer therapeutics,along with their inherent advantages and associated challenges,as well as recent research advances.
基金Supported by Italian Ministry of Research,Apulia Region,European Commission and National Council of Research
文摘Modern medicine is expanding the possibilities of receiving "personalized" diagnosis and therapies,providing minimal invasiveness,technological solutions based on non-ionizing radiation,early detection of pathologies with the main objectives of being operator independent and with low cost to society.Our research activities aim to strongly contribute to these trends by improving the capabilities of current diagnostic imaging systems,which are of key importance in possibly providing both optimal diagnosis and therapies to patients.In medical diagnostics,cellular imaging aims to develop new methods and technologies for the detection of specific metabolic processes in living organisms,in order to accurately identify and discriminate normal from pathological tissues.In fact,most diseases have a "molecular basis" that detected through these new diagnostic methodologies can provide enormous benefits to medicine.Nowadays,this possibility is mainly related to the use of Positron Emission Tomography,with an exposure to ionizing radiation for patients and operators and with extremely high medical diagnosticscosts.The future possible development of non-ionizing cellular imaging based on techniques such as Nuclear Magnetic Resonance or Ultrasound,would represent an important step towards modern and personalized therapies.During the last decade,the field of nanotechnology has made important progress and a wide range of organic and inorganic nanomaterials are now available with an incredible number of further combinations with other compounds for cellular targeting.The availability of these new advanced nanosystems allows new scenarios in diagnostic methodologies which are potentially capable of providing morphological and functional information together with metabolic and cellular indications.
基金Supported by Bando Laboratori,DD MIUR 14.5.2005 n.602/Ric/2005 of the Italian Ministry of Instruction and Research,No.DM18604by FESR P.O.Apulia Region 2007-2013,Action 1.2.4,No.3Q5AX31by the Progetto Bandiera NANOMAX ENCODER
文摘Since the recognition of disease molecular basis,it has become clear that the keystone moments of medical practice,namely early diagnosis,appropriate therapeutic treatment and patient follow-up,must be approached at a molecular level.These objectives will be in the near future more effectively achievable thanks to the impressive developments in nanotechnologies and their applications to the biomedical field,starting-up the nanomedicine era.The continuous advances in the development of biocompatible smart nanomaterials,in particular,will be crucial in several aspects of medicine.In fact,the possibility of manufacturing nanoparticle contrast agents that can be selectively targeted to specific pathological cells has extended molecular im-aging applications to non-ionizing techniques and,at the same time,has made reachable the perspective of combining highly accurate diagnoses and personalized therapies in a single theranostic intervention.Main developing applications of nanosized theranostic agents include targeted molecular imaging,controlled drug release,therapeutic monitoring,guidance of radiationbased treatments and surgical interventions.Here we will review the most recent findings in nanoparticles contrast agents and their applications in the field of cancer molecular imaging employing non-ionizing techniques and disease-specific contrast agents,with special focus on recent findings on those nanomaterials particularly promising for ultrasound molecular imaging and simultaneous treatment of cancer.
文摘Recombinant technology-based vaccines have emerged as a highly effective way to prevent a wide range of illnesses.The technology improved vaccine manufacturing,rendering it more efficient and economical.These vaccines have multiple advantages compared to conventional vaccines.The pandemic has heightened awareness of the advantages of these vaccine technologies;trust and acceptance of these vaccines are steadily growing globally.This work offers an overview of the prospects and advantages associated with recombinant vaccines.Additionally,it discusses some of the challenges likely to arise in the future.Their ability to target diverse pathogen classes underscores their contributions to preventing previously untreatable diseases(especially vector-borne and emerging diseases)and hurdles faced throughout the vaccine development process,especially in enhancing the effectiveness of these vaccines.Moreover,their compatibility with emerging vaccination platforms of the future like virus-like particles and CRISPR/Cas9 for the production of next-generation vaccines may offer many prospects.This review also reviewed the hurdles faced throughout the vaccine development process,especially in enhancing the effectiveness of these vaccines against vector-borne diseases,emerging diseases,and untreatable diseases with high mortality rates like AIDS as well as cancer.
基金the Project of China-Japan Joint International Laboratory of Advanced Drug Delivery System Research and Translation of Liaoning Province(No.2024JH2/102100007)Basic research project of 2024 Liaoning Provincial Department of Education Program(No.LJ212410163045)+1 种基金Liaoning Provincial Department of Education Program(No.LJKMZ20221353)the open fund of National Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers(No.2024-KFB-003).
文摘Photodynamic therapy(PDT)has been extensively investigated as an alternative cancer treatment;however,its efficacy is limited by the low oxygen content and excess glutathione(GSH)in tumor tissues.With the emergence of ferroptosis,which also impacts redox homeostasis,a combined PDT-ferroptosis approach holds promise for amplifying the efficacy of both treatments.However,concerns persist regarding biocompatibility and tumor-specific release.Here,we report a self-motivated co-nanoassembly for combined PDT and ferroptosis-driven tumor therapy.We first modify linoleic acid with protoporphyrin Ⅸ to form a lipidic derivative(denoted as PLA)and develop a light-boosted carrier-free nanoplatform(PLA@R NPs)by co-assembling the ferroptosis inducer RAS-selective lethal 3(RSL3)and PLA.Upon light irradiation,reactive oxygen species produced by PDT trigger linoleic acid peroxidation,leading to the destruction of the nanoparticles and the release of RSL3.The rapid release of RSL3 enhances PDT sensitivity by depleting GSH and utilizing the Fenton reaction to supplement oxygen.Additionally,PDT accelerates lipid peroxidation,further inducing ferroptosis.This self-motivated effect increases oxidative stress in tumor tissues,as confirmed by a tumor-on-a-chip model.Moreover,the in vivo therapeutic effect with the PLA@R NPs is significant,demonstrating the promising potential of combining PDT and ferroptosis using a light-boosted and self-motivated nanoplatform.
文摘In the United States,1 in 10 infants are born preterm.The majority of neonatal deaths and nearly a third of infant deaths are linked to preterm birth.Preterm birth is initiated when the quiescent state of the uterus ends prematurely,leading to contractions and parturition beginning as early as 32 weeks,though the origins are not well understood.To enable research and discovery of therapeutics with potential to better address preterm birth,the capability to study isolated cell processes of pregnant uterine tissue in vitro is needed.Our development of an in vitro model of the myometrium utilizing human uterine smooth muscle cells(uSMCs)responsible for contractions provides a methodology to examine cellular mechanisms of late-stage pregnancy potentially involved in preterm birth.We discuss culture of uSMCs on a flexible polydimethylsiloxane(PDMS)substrate functionalized with cationic poly-L-lysine(PLL),followed by extracellular matrix(ECM)protein coating.Previous work exploring uSMC behavior on PDMS substrates have utilized collagen-I coatings,however,we demonstrated the first exploration of human uSMC response to strain on fibronectin-coated flexible membranes,importantly reflecting the significant increase of fibronectin content found in the myometrial ECM during late-stage pregnancy.Using the model we developed,we conducted proof-of-concept studies to investigate the impact of substrate strain on uSMC cell morphology and gene expression.It was found that PLL and varied ECM protein coatings(collagen I,collagen III,and fibronectin)altered cell nuclei morphology and density on PDMS substrates.Additionally,varied strain rates applied to uSMC substrates significantly impacted uSMC gene expression of IL-6,a cytokine associated with instances of preterm labor.These results suggest that both surface and mechanical properties of in vitro systems impact primary human uSMC phenotype and offer uSMC culture methodologies that can be utilized to further the understanding of cellular pathways involved in the uterus under mechanical load.
