Noninvasive drug delivery systems are well applied due to their safety,convenience,and patient compliance[1].However,drug permeability in traditional noninvasive drug delivery systems is limited,and it is difficult to...Noninvasive drug delivery systems are well applied due to their safety,convenience,and patient compliance[1].However,drug permeability in traditional noninvasive drug delivery systems is limited,and it is difficult to regulate the administration time and dosage[2].The depth of drug permeability is mainly impeded by geometry obstruction and diffusional resistance of the stratum corneum,which consists of 10 to 30 layers of keratinized corneocytes embedded in an extracellular lipid matrix.It is a great challenge to overcome stratum corneum to enhance drug permeation across skin[3].The latest publication in Advanced Materials from the teams of Cai,Cui,and Bai introduced a new type of nanobubble ultrasonic coupling hydrogel,which is built by dynamic Schiff base cross-linking between nanobubbles and aminated hyaluronic acid(HA)[4].This ultrasound coupling hydrogel opens new insights in noninvasive drug delivery because it effciently overcomes the skin barrier and achieves precise spatiotemporal drug delivery by ultrasound-amplified cavitation effect.展开更多
Microneedles(MNs)are a prospective system in cancer immunotherapy to overcome barriers regarding proper antigen delivery and presentation.This study aims at identifying the potential of MNs for the delivery of Peptide...Microneedles(MNs)are a prospective system in cancer immunotherapy to overcome barriers regarding proper antigen delivery and presentation.This study aims at identifying the potential of MNs for the delivery of Peptide-coated Conditionally Replicating Adenoviruses(PeptiCRAd),whereby peptides enhance the immunogenic properties of adenoviruses presenting tumor associated antigens.The combination of PeptiCRAd with MNs containing polyvinylpyrrolidone and sucrose was tested for the preservation of structure,induction of immune response,and tumor eradication.The findings indicated that MN-delivered PeptiCRAd was effective in peptide presentation in vivo,leading to complete tumor rejection when mice were pre-vaccinated.A rise in the cDC1 population in the lymph nodes of the MN treated mice led to an increase in the effector memory T cells in the body.Thus,the results of this study demonstrate that the combination of MN technology with PeptiCRAd may provide a safer,more tolerable,and efficient approach to cancer immunotherapy,potentially translatable to other therapeutic applications.展开更多
Collagen-based materials,renowned for their biocompatibility and minimal immunogenicity,serve as exemplary substrates in a myriad of biomedical applications.Collagen-based micro/nanogels,in particular,are valued for t...Collagen-based materials,renowned for their biocompatibility and minimal immunogenicity,serve as exemplary substrates in a myriad of biomedical applications.Collagen-based micro/nanogels,in particular,are valued for their increased surface area,tunable degradation rates,and ability to facilitate targeted drug delivery,making them instrumental in advanced therapeutics and tissue engineering endeavors.Although extensive reviews on micro/nanogels exist,they tend to cover a wide range of biomaterials and lack a specific focus on collagen-based materials.The current review offers an in-depth look into the manufacturing technologies,drug release mechanisms,and biomedical applications of collagen-based micro/nanogels to address this gap.First,we provide an overview of the synthetic strategies that allow the precise control of the size,shape,and mechanical strength of these collagen-based micro/nanogels by controlling the degree of cross-linking of the materials.These properties are crucial for their performance in biomedical applications.We then highlight the environmental responsiveness of these collagen-based micro/nanogels,particularly their sensitivity to enzymes and pH,which enables controlled drug release under various pathological conditions.The discussion then expands to include their applications in cancer therapy,antimicrobial treatments,bone tissue repair,and imaging diagnosis,emphasizing their versatility and potential in these critical areas.The challenges and future perspectives of collagen-based micro/nanogels in the field are discussed at the end of the review,with an emphasis on the translation to clinical practice.This comprehensive review serves as a valuable resource for researchers,clinicians,and scientists alike,providing insights into the current state and future directions of collagen-based micro/nanogel research and development.展开更多
Metal-organic frameworks(MOFs)hold promise as theranostic carriers for atherosclerosis.However,to further advance their therapeutic effects with higher complexity and functionality,integrating multiple components with...Metal-organic frameworks(MOFs)hold promise as theranostic carriers for atherosclerosis.However,to further advance their therapeutic effects with higher complexity and functionality,integrating multiple components with complex synthesis procedures are usually involved.Here,we reported a facile and general strategy to prepare multifunctional anti-atherosclerosis theranostic platform in a single-step manner.A custom-designed multifunctional polymer,poly(butyl methacrylate-co-methacrylic acid)branched phosphorylatedβ-glucan(PBMMA-PG),can effectively entrap different MOFs via coordination,simultaneously endow the MOF with enhanced stability,lesional macrophages selectivity and enhanced endosome escape.Sequential ex situ char-acterization and computational studies elaborated the potential mechanism.This facile post-synthetic modifi-cation granted the administered nanoparticles atherosclerotic tropism by targeting Dectin-1+macrophages,enhancing in situ MR signal intensity by 72%.Delivery of siNLRP3 effectively mitigated NLRP3 inflammasomes activation,resulting a 43%reduction of plaque area.Overall,the current study highlights a simple and general approach for fabricating a MOF-based theranostic platform towards atherosclerosis conditioning,which may also expand to other indications targeting the lesional macrophages.展开更多
Immune cells play a crucial regulatory role in inflammatory phase and proliferative phase during skin healing.How to programmatically activate sequential immune responses is the key for scarless skin regeneration.In t...Immune cells play a crucial regulatory role in inflammatory phase and proliferative phase during skin healing.How to programmatically activate sequential immune responses is the key for scarless skin regeneration.In this study,an“Inner-Outer”IL-10-loaded electrospun fiber with cascade release behavior was constructed.During the inflammatory phase,the electrospun fiber released a lower concentration of IL-10 within the wound,inhibiting excessive recruitment of inflammatory cells and polarizing macrophages into anti-inflammatory phenotype“M2c”to suppress excessive inflammation response.During the proliferative phase,a higher concentration of IL-10 released by the fiber and the anti-fibrotic cytokines secreted by polarized“M2c”directly acted on dermal fibroblasts to simultaneously inhibit extracellular matrix overdeposition and promote fibroblast migration.The“Inner-Outer”IL-10-loaded electrospun fiber programmatically activated the sequential immune responses during wound healing and led to scarless skin regeneration,which is a promising immunomodulatory biomaterial with great potential for promoting complete tissue regeneration.展开更多
Hydrogel microspheres,with their high water content and tunable physicochemical properties,have emerged as a promising class of materials for a myriad of biomedical applications.1 These microscale particles,which can ...Hydrogel microspheres,with their high water content and tunable physicochemical properties,have emerged as a promising class of materials for a myriad of biomedical applications.1 These microscale particles,which can be fabricated from both natural and synthetic polymers,exhibit diverse properties and bear a striking resemblance to the native extracellular matrix.2 This makes them highly suitable as substrates for cell culture,templates for tissue engineering,and vehicles for drug and protein delivery.展开更多
Remarkable progress in phototherapy has been made in recent decades,due to its non-invasiveness and instant therapeutic efficacy.In addition,with the rapid development of nanoscience and nanotechnology,phototherapy sy...Remarkable progress in phototherapy has been made in recent decades,due to its non-invasiveness and instant therapeutic efficacy.In addition,with the rapid development of nanoscience and nanotechnology,phototherapy systems based on nanoparticles or nanocomposites also evolved as an emerging hotspot in nanomedicine research,especially in cancer.In this review,first we briefly introduce the history of phototherapy,and the mechanisms of phototherapy in cancer treatment.Then,we summarize the representative development over the past three to five years in nanoparticle-based phototherapy and highlight the design of the innovative nanoparticles thereof.Finally,we discuss the feasibility and the potential of the nanoparticle-based phototherapy systems in clinical anticancer therapeutic applications,aiming to predict future research directions in this field.Our review is a tutorial work,aiming at providing useful insights to researchers in the field of nanotechnology,nanoscience and cancer.展开更多
Antioxidant collagen hydrolysates refers to the peptides mixture with antioxidant properties identified from hydrolyzed collagen.Due to its specific structural,biological and physicochemical properties,collagen hydrol...Antioxidant collagen hydrolysates refers to the peptides mixture with antioxidant properties identified from hydrolyzed collagen.Due to its specific structural,biological and physicochemical properties,collagen hydrolysates have been explored as a multifunctional antioxidant in the biomedical field.In this review,we summarize recent advances in antioxidant collagen hydrolysates development.Initially,the preparation process of antioxidant collagen hydrolysates is introduced,including the production and separation methods.Then the effects and the mechanisms of amino acid composition and collagen peptide structure on the antioxidant activity of collagen hydrolysates are reviewed.Finally,the applications of antioxidant collagen hydrolysates in biomedical domains are summarized,with critical discussions about the advantages,current limitations and challenges to be resolved in the future.展开更多
Oral insulin delivery could change the life of millions of diabetic patients as an effective,safe,easy-to-use,and affordable alternative to insulin injections,known by an inherently thwarted patient compliance.Here,we...Oral insulin delivery could change the life of millions of diabetic patients as an effective,safe,easy-to-use,and affordable alternative to insulin injections,known by an inherently thwarted patient compliance.Here,we designed a multistage nanoparticle(NP)system capable of circumventing the biological barriers that lead to poor drug absorption and bioavailability after oral administration.The nanosystem consists of an insulin-loaded porous silicon NP encapsulated into a pH-responsive lignin matrix,and surface-functionalized with the Fc fragment of immunoglobulin G,which acts as a targeting ligand for the neonatal Fc receptor(FcRn).The developed NPs presented small size(211±1 nm)and narrow size distribution.The NPs remained intact in stomach and intestinal pH conditions,releasing the drug exclusively at pH 7.4,which mimics blood circulation.This formulation showed to be highly cytocompatible,and surface plasmon resonance studies demonstrated that FcRn-targeted NPs present higher capacity to interact and being internalized by the Caco-2 cells,which express FcRn,as demonstrated by Western blot.Ultimately,in vitro permeability studies showed that Fc-functionalized NPs induced an increase in the amount of insulin that permeated across a Caco-2/HT29-MTX co-culture model,showing apparent permeability coefficients(Papp)of 2.37×106 cm/s,over the 1.66×106 cm/s observed for their non-functionalized counterparts.Overall,these results demonstrate the potential of these NPs for oral delivery of anti-diabetic drugs.展开更多
Thrombosis and infections are the two major complications associated with extracorporeal circuits and indwelling medical devices,leading to significant mortality in clinic.To address this issue,here,we report a biomim...Thrombosis and infections are the two major complications associated with extracorporeal circuits and indwelling medical devices,leading to significant mortality in clinic.To address this issue,here,we report a biomimetic surface engineering strategy by the integration of mussel-inspired adhesive peptide,with bio-orthogonal click chemistry,to tailor the surface functionalities of tubing and catheters.Inspired by mussel adhesive foot protein,a bioclickable peptide mimic(DOPA)4-azidebased structure is designed and grafted on an aminated tubing robustly based on catechol-amine chemistry.Then,the dibenzylcyclooctyne(DBCO)modified nitric oxide generating species of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA)chelated copper ions and the DBCO-modified antimicrobial peptide(DBCO-AMP)are clicked onto the grafted surfaces via bio-orthogonal reaction.The combination of the robustly grafted AMP and Cu-DOTA endows the modified tubing with durable antimicrobial properties and ability in long-term catalytically generating NO from endogenous snitrosothiols to resist adhesion/activation of platelets,thus preventing the formation of thrombosis.Overall,this biomimetic surface engineering technology provides a promising solution for multicomponent surface functionalization and the surface bioengineering of biomedical devices with enhanced clinical performance.展开更多
Background:Transcriptomic and proteomic profiling of human brain tissue is hindered by the availability of fresh samples from living patients.Postmortem samples usually represent the advanced disease stage of the pati...Background:Transcriptomic and proteomic profiling of human brain tissue is hindered by the availability of fresh samples from living patients.Postmortem samples usually represent the advanced disease stage of the patient.Fur-thermore,the postmortem interval can affect the transcriptomic and proteomic profiles.Therefore,fresh brain tissue samples from living patients represent a valuable resource of metabolically intact tissue.Implantation of deep brain stimulation(DBS)electrodes into the human brain is a neurosurgical treatment for,e.g.,movement disorders.Here,we describe an improved approach to collecting brain tissues from surgical instruments used in implantation of DBS device for transcriptomics and proteomics analyses.Methods:Samples were extracted from guide tubes and recording electrodes used in routine DBS implantation procedure to treat patients with Parkinson’s disease,genetic dystonia and tremor.RNA sequencing was performed in tissues extracted from the recording microelectrodes and liquid chromatography-mass spectrometry(LC-MS)per-formed in tissues from guide tubes.To assess the performance of the current approach,the obtained datasets were compared with previously published datasets representing brain tissues.Results:Altogether,32,034 RNA transcripts representing the unique Ensembl gene identifiers were detected from eight samples representing both hemispheres of four patients.By using LC-MS,we identified 734 unique proteins from 31 samples collected from 14 patients.The datasets are available in the BioStudies database(accession number S-BSST667).Our results indicate that surgical instruments used in DBS installation retain brain material sufficient for protein and gene expression studies.Comparison with previously published datasets obtained with similar approach proved the robustness and reproducibility of the protocol.Conclusions:The instruments used during routine DBS surgery are a useful source for obtaining fresh brain tis-sues from living patients.This approach overcomes the issues that arise from using postmortem tissues,such as the effect of postmortem interval on transcriptomic and proteomic landscape of the brain,and can be used for studying molecular aspects of DBS-treatable diseases.展开更多
Tuberculosis(TB),caused by Mycobacterium tuberculosis,continues to pose a significant threat to global health.The resilience of TB is amplified by a myriad of physical,biological,and biopharmaceutical barriers that ch...Tuberculosis(TB),caused by Mycobacterium tuberculosis,continues to pose a significant threat to global health.The resilience of TB is amplified by a myriad of physical,biological,and biopharmaceutical barriers that challenge conventional therapeutic approaches.This review navigates the intricate landscape of TB treatment,from the stealth of latent infections and the strength of granuloma formations to the daunting specters of drug resistance and altered gene expression.Amidst these challenges,traditional therapies often fail,contending with inconsistent bioavailability,prolonged treatment regimens,and socioeconomic burdens.Nanoscale Drug Delivery Systems(NDDSs)emerge as a promising beacon,ready to overcome these barriers,offering better drug targeting and improved patient adherence.Through a critical approach,we evaluate a spectrum of nanosystems and their efficacy against MTB both in vitro and in vivo.This review advocates for the intensification of research in NDDSs,heralding their potential to reshape the contours of global TB treatment strategies.展开更多
基金support from the UMCG Research Fundssupport from China Scholarship Council.
文摘Noninvasive drug delivery systems are well applied due to their safety,convenience,and patient compliance[1].However,drug permeability in traditional noninvasive drug delivery systems is limited,and it is difficult to regulate the administration time and dosage[2].The depth of drug permeability is mainly impeded by geometry obstruction and diffusional resistance of the stratum corneum,which consists of 10 to 30 layers of keratinized corneocytes embedded in an extracellular lipid matrix.It is a great challenge to overcome stratum corneum to enhance drug permeation across skin[3].The latest publication in Advanced Materials from the teams of Cai,Cui,and Bai introduced a new type of nanobubble ultrasonic coupling hydrogel,which is built by dynamic Schiff base cross-linking between nanobubbles and aminated hyaluronic acid(HA)[4].This ultrasound coupling hydrogel opens new insights in noninvasive drug delivery because it effciently overcomes the skin barrier and achieves precise spatiotemporal drug delivery by ultrasound-amplified cavitation effect.
基金support from the Research Council Finland(grant No.331151,HAS)UMCG Research Funds(HAS)+6 种基金the Finnish Cultural Foundation(CD)provided by the European Research Council(ERC)under the Horizon 2020 framework(grant No.681219,VC)the Magnus Ehrnrooth Foundation(project No.4706235,VC)the Jane and Aatos Erkko Foundation(project No.4705796,VC)the Finnish Cancer Foundation(project No.4706116,VC)the Helsinki Institute of Life Science(HiLIFE)(project No.797011004,VC)the Digital Precision Cancer Medicine Flagship iCAN(VC),and the GeneCellNano Flagship(VC).
文摘Microneedles(MNs)are a prospective system in cancer immunotherapy to overcome barriers regarding proper antigen delivery and presentation.This study aims at identifying the potential of MNs for the delivery of Peptide-coated Conditionally Replicating Adenoviruses(PeptiCRAd),whereby peptides enhance the immunogenic properties of adenoviruses presenting tumor associated antigens.The combination of PeptiCRAd with MNs containing polyvinylpyrrolidone and sucrose was tested for the preservation of structure,induction of immune response,and tumor eradication.The findings indicated that MN-delivered PeptiCRAd was effective in peptide presentation in vivo,leading to complete tumor rejection when mice were pre-vaccinated.A rise in the cDC1 population in the lymph nodes of the MN treated mice led to an increase in the effector memory T cells in the body.Thus,the results of this study demonstrate that the combination of MN technology with PeptiCRAd may provide a safer,more tolerable,and efficient approach to cancer immunotherapy,potentially translatable to other therapeutic applications.
基金This study was supported by grants from the National Natural Science Foundation of China(No.52242208)the National Natural Science Foundation of China(No.82371964)+1 种基金the Sigrid Jusélius Foundation,the Research Council of Finland(Academy Research Fellowship Grant No.354421)the European Union(ERC,BioLure,No.101115752).
文摘Collagen-based materials,renowned for their biocompatibility and minimal immunogenicity,serve as exemplary substrates in a myriad of biomedical applications.Collagen-based micro/nanogels,in particular,are valued for their increased surface area,tunable degradation rates,and ability to facilitate targeted drug delivery,making them instrumental in advanced therapeutics and tissue engineering endeavors.Although extensive reviews on micro/nanogels exist,they tend to cover a wide range of biomaterials and lack a specific focus on collagen-based materials.The current review offers an in-depth look into the manufacturing technologies,drug release mechanisms,and biomedical applications of collagen-based micro/nanogels to address this gap.First,we provide an overview of the synthetic strategies that allow the precise control of the size,shape,and mechanical strength of these collagen-based micro/nanogels by controlling the degree of cross-linking of the materials.These properties are crucial for their performance in biomedical applications.We then highlight the environmental responsiveness of these collagen-based micro/nanogels,particularly their sensitivity to enzymes and pH,which enables controlled drug release under various pathological conditions.The discussion then expands to include their applications in cancer therapy,antimicrobial treatments,bone tissue repair,and imaging diagnosis,emphasizing their versatility and potential in these critical areas.The challenges and future perspectives of collagen-based micro/nanogels in the field are discussed at the end of the review,with an emphasis on the translation to clinical practice.This comprehensive review serves as a valuable resource for researchers,clinicians,and scientists alike,providing insights into the current state and future directions of collagen-based micro/nanogel research and development.
基金financial support from Seed Funding from Second Affiliated Hospital of Zhejiang University School of Medicine.Z.Liu acknowledges financial support from Academy of Finland(No.340129)Finnish Foundation for Cardiovascular Research.Prof.H.A.Santos acknowledges financial support from Academy of Finland(No.331151)+3 种基金the UMCG Research Funds.H.Gao acknowledges financial support from the Chinese Scholarship Council(No.202006090004)financial support European Union’s Horizon Europe 2021 Research and Innovation Programme for her Marie Skło-dowska-Curie(No.101059391)financial support from National Natural Science Foundation of China(No.52072392,52472290)the financial support from Shanghai Super Post-Doctor Incentive Program(No.2022665).
文摘Metal-organic frameworks(MOFs)hold promise as theranostic carriers for atherosclerosis.However,to further advance their therapeutic effects with higher complexity and functionality,integrating multiple components with complex synthesis procedures are usually involved.Here,we reported a facile and general strategy to prepare multifunctional anti-atherosclerosis theranostic platform in a single-step manner.A custom-designed multifunctional polymer,poly(butyl methacrylate-co-methacrylic acid)branched phosphorylatedβ-glucan(PBMMA-PG),can effectively entrap different MOFs via coordination,simultaneously endow the MOF with enhanced stability,lesional macrophages selectivity and enhanced endosome escape.Sequential ex situ char-acterization and computational studies elaborated the potential mechanism.This facile post-synthetic modifi-cation granted the administered nanoparticles atherosclerotic tropism by targeting Dectin-1+macrophages,enhancing in situ MR signal intensity by 72%.Delivery of siNLRP3 effectively mitigated NLRP3 inflammasomes activation,resulting a 43%reduction of plaque area.Overall,the current study highlights a simple and general approach for fabricating a MOF-based theranostic platform towards atherosclerosis conditioning,which may also expand to other indications targeting the lesional macrophages.
基金This work was supported by the National Key Research and Development Program of China(2020YFA0908200)National Natural Science Foundation of China(81701907 and 81871472)+7 种基金The in vitro biological experiment was supported by National Natural Science Foundation of China(81772099 and 81801928)Shanghai Sailing Program(18YF1412400)The production and detection of the scaffold were supported by Shanghai Jiao Tong University“Medical and Research”Program(ZH2018ZDA04)Science and Technology Commission of Shanghai Municipality(19440760400)The in vivo biological experiment were supported Pujiang program of SSTC(18PJ1407100)Prof.H.Zhang acknowledges the financial support from Academy of Finland(328933)Sigrid Juselius Foundation(28001830K1)Prof.H.A.Santos acknowledges the financial support from HiLIFE Research Funds and Sigrid Juselius Foundation.
文摘Immune cells play a crucial regulatory role in inflammatory phase and proliferative phase during skin healing.How to programmatically activate sequential immune responses is the key for scarless skin regeneration.In this study,an“Inner-Outer”IL-10-loaded electrospun fiber with cascade release behavior was constructed.During the inflammatory phase,the electrospun fiber released a lower concentration of IL-10 within the wound,inhibiting excessive recruitment of inflammatory cells and polarizing macrophages into anti-inflammatory phenotype“M2c”to suppress excessive inflammation response.During the proliferative phase,a higher concentration of IL-10 released by the fiber and the anti-fibrotic cytokines secreted by polarized“M2c”directly acted on dermal fibroblasts to simultaneously inhibit extracellular matrix overdeposition and promote fibroblast migration.The“Inner-Outer”IL-10-loaded electrospun fiber programmatically activated the sequential immune responses during wound healing and led to scarless skin regeneration,which is a promising immunomodulatory biomaterial with great potential for promoting complete tissue regeneration.
文摘Hydrogel microspheres,with their high water content and tunable physicochemical properties,have emerged as a promising class of materials for a myriad of biomedical applications.1 These microscale particles,which can be fabricated from both natural and synthetic polymers,exhibit diverse properties and bear a striking resemblance to the native extracellular matrix.2 This makes them highly suitable as substrates for cell culture,templates for tissue engineering,and vehicles for drug and protein delivery.
基金The Academy of Finland(Grants Nos.331151 and 331106),the Sigrid Jus´elius Foundation,the China Scholarship Council,and the UMCG Research Funds are acknowledged for financial support.
文摘Remarkable progress in phototherapy has been made in recent decades,due to its non-invasiveness and instant therapeutic efficacy.In addition,with the rapid development of nanoscience and nanotechnology,phototherapy systems based on nanoparticles or nanocomposites also evolved as an emerging hotspot in nanomedicine research,especially in cancer.In this review,first we briefly introduce the history of phototherapy,and the mechanisms of phototherapy in cancer treatment.Then,we summarize the representative development over the past three to five years in nanoparticle-based phototherapy and highlight the design of the innovative nanoparticles thereof.Finally,we discuss the feasibility and the potential of the nanoparticle-based phototherapy systems in clinical anticancer therapeutic applications,aiming to predict future research directions in this field.Our review is a tutorial work,aiming at providing useful insights to researchers in the field of nanotechnology,nanoscience and cancer.
基金supported by grants from the National Natural Science Foundation of China(No.52242208).
文摘Antioxidant collagen hydrolysates refers to the peptides mixture with antioxidant properties identified from hydrolyzed collagen.Due to its specific structural,biological and physicochemical properties,collagen hydrolysates have been explored as a multifunctional antioxidant in the biomedical field.In this review,we summarize recent advances in antioxidant collagen hydrolysates development.Initially,the preparation process of antioxidant collagen hydrolysates is introduced,including the production and separation methods.Then the effects and the mechanisms of amino acid composition and collagen peptide structure on the antioxidant activity of collagen hydrolysates are reviewed.Finally,the applications of antioxidant collagen hydrolysates in biomedical domains are summarized,with critical discussions about the advantages,current limitations and challenges to be resolved in the future.
基金Dr.Shiqi Wang acknowledges financial support from Academy of Finland(decision no.331106)Prof.H´elder A.Santos acknowledges financial support from the HiLIFE Research Funds,the Sigrid Jus´elius Foundation(decision no.4704580)+1 种基金the Academy of Finland(grant no.317042 and 331151)The authors acknowledge the following core facilities funded by Biocenter Finland:Electron Microscopy Unity of the University of Helsinki,Finland for providing the facilities for TEM imaging.The authors acknowledge the use of ALD center Finland research infrastructure for EDX measurements.The authors acknowledge Tomas Bauleth-Ramos for technical support with the cell viability assays.
文摘Oral insulin delivery could change the life of millions of diabetic patients as an effective,safe,easy-to-use,and affordable alternative to insulin injections,known by an inherently thwarted patient compliance.Here,we designed a multistage nanoparticle(NP)system capable of circumventing the biological barriers that lead to poor drug absorption and bioavailability after oral administration.The nanosystem consists of an insulin-loaded porous silicon NP encapsulated into a pH-responsive lignin matrix,and surface-functionalized with the Fc fragment of immunoglobulin G,which acts as a targeting ligand for the neonatal Fc receptor(FcRn).The developed NPs presented small size(211±1 nm)and narrow size distribution.The NPs remained intact in stomach and intestinal pH conditions,releasing the drug exclusively at pH 7.4,which mimics blood circulation.This formulation showed to be highly cytocompatible,and surface plasmon resonance studies demonstrated that FcRn-targeted NPs present higher capacity to interact and being internalized by the Caco-2 cells,which express FcRn,as demonstrated by Western blot.Ultimately,in vitro permeability studies showed that Fc-functionalized NPs induced an increase in the amount of insulin that permeated across a Caco-2/HT29-MTX co-culture model,showing apparent permeability coefficients(Papp)of 2.37×106 cm/s,over the 1.66×106 cm/s observed for their non-functionalized counterparts.Overall,these results demonstrate the potential of these NPs for oral delivery of anti-diabetic drugs.
基金the National Natural Science Foundation of China(Project 82072072)(Z.Y)International Cooperation Project by Science and Technology Department of Sichuan Province(2021YFH0056 and 2019YFH0103)(Z.Y)the Fundamental Research Funds for the Central Universities(2682020ZT82 and 2682020ZT76)(Z.Y).
文摘Thrombosis and infections are the two major complications associated with extracorporeal circuits and indwelling medical devices,leading to significant mortality in clinic.To address this issue,here,we report a biomimetic surface engineering strategy by the integration of mussel-inspired adhesive peptide,with bio-orthogonal click chemistry,to tailor the surface functionalities of tubing and catheters.Inspired by mussel adhesive foot protein,a bioclickable peptide mimic(DOPA)4-azidebased structure is designed and grafted on an aminated tubing robustly based on catechol-amine chemistry.Then,the dibenzylcyclooctyne(DBCO)modified nitric oxide generating species of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA)chelated copper ions and the DBCO-modified antimicrobial peptide(DBCO-AMP)are clicked onto the grafted surfaces via bio-orthogonal reaction.The combination of the robustly grafted AMP and Cu-DOTA endows the modified tubing with durable antimicrobial properties and ability in long-term catalytically generating NO from endogenous snitrosothiols to resist adhesion/activation of platelets,thus preventing the formation of thrombosis.Overall,this biomimetic surface engineering technology provides a promising solution for multicomponent surface functionalization and the surface bioengineering of biomedical devices with enhanced clinical performance.
基金the Academy of Finland(Decision Numbers#311934 R.H.[profiling programme]and#331436 J.U.),Pediatric Research Foundation,Finland(J.U.and R.H.),Biocenter Oulu(J.U.and R.H.),Biocenter Finland,Special State Grants for Health Research,Oulu University Hospital,Finland(J.U.)the Terttu Foundation,Oulu University Hospital,Finland(J.K.).
文摘Background:Transcriptomic and proteomic profiling of human brain tissue is hindered by the availability of fresh samples from living patients.Postmortem samples usually represent the advanced disease stage of the patient.Fur-thermore,the postmortem interval can affect the transcriptomic and proteomic profiles.Therefore,fresh brain tissue samples from living patients represent a valuable resource of metabolically intact tissue.Implantation of deep brain stimulation(DBS)electrodes into the human brain is a neurosurgical treatment for,e.g.,movement disorders.Here,we describe an improved approach to collecting brain tissues from surgical instruments used in implantation of DBS device for transcriptomics and proteomics analyses.Methods:Samples were extracted from guide tubes and recording electrodes used in routine DBS implantation procedure to treat patients with Parkinson’s disease,genetic dystonia and tremor.RNA sequencing was performed in tissues extracted from the recording microelectrodes and liquid chromatography-mass spectrometry(LC-MS)per-formed in tissues from guide tubes.To assess the performance of the current approach,the obtained datasets were compared with previously published datasets representing brain tissues.Results:Altogether,32,034 RNA transcripts representing the unique Ensembl gene identifiers were detected from eight samples representing both hemispheres of four patients.By using LC-MS,we identified 734 unique proteins from 31 samples collected from 14 patients.The datasets are available in the BioStudies database(accession number S-BSST667).Our results indicate that surgical instruments used in DBS installation retain brain material sufficient for protein and gene expression studies.Comparison with previously published datasets obtained with similar approach proved the robustness and reproducibility of the protocol.Conclusions:The instruments used during routine DBS surgery are a useful source for obtaining fresh brain tis-sues from living patients.This approach overcomes the issues that arise from using postmortem tissues,such as the effect of postmortem interval on transcriptomic and proteomic landscape of the brain,and can be used for studying molecular aspects of DBS-treatable diseases.
基金support from the S˜ao Paulo Research Foundation(FAPESP,Brazil),Grant numbers#01664-1,#2022/02661-3 and#2020/16573-3,respectivelyNational Council for Scientific and Technological Development(CNPq):Productivity Research Fellows(PQ CNPq):305408/2022-4This study is part of the National Institute of Science and Technology in Pharmaceutical Nanotechnology:a transdisciplinary approach,INCT-NANOFARMA,which is supported by S˜ao Paulo Research Foundation(FAPESP,Brazil)Grant#2014/50928-2,and by“Conselho Nacional de Desenvolvimento Científico e Tecnol′ogico”(CNPq,Brazil)Grant#465687/2014-8.Prof.H.A.Santos acknowledges financial support from the Research Council of Finland(Grant No.331151)and the UMCG Research Funds.
文摘Tuberculosis(TB),caused by Mycobacterium tuberculosis,continues to pose a significant threat to global health.The resilience of TB is amplified by a myriad of physical,biological,and biopharmaceutical barriers that challenge conventional therapeutic approaches.This review navigates the intricate landscape of TB treatment,from the stealth of latent infections and the strength of granuloma formations to the daunting specters of drug resistance and altered gene expression.Amidst these challenges,traditional therapies often fail,contending with inconsistent bioavailability,prolonged treatment regimens,and socioeconomic burdens.Nanoscale Drug Delivery Systems(NDDSs)emerge as a promising beacon,ready to overcome these barriers,offering better drug targeting and improved patient adherence.Through a critical approach,we evaluate a spectrum of nanosystems and their efficacy against MTB both in vitro and in vivo.This review advocates for the intensification of research in NDDSs,heralding their potential to reshape the contours of global TB treatment strategies.
