The critical factor of spatial constraint,provided by the external confinement(e.g.,matrix),is often overlooked during photodynamic inactivation,despite playing a crucial role in determining the molecular photophysica...The critical factor of spatial constraint,provided by the external confinement(e.g.,matrix),is often overlooked during photodynamic inactivation,despite playing a crucial role in determining the molecular photophysical process and subsequent antipathogen performance.Here,as a proof-of-concept model,we employed two types of polymers with varying interaction energies with dopants to investigate the intrinsic relationship between spatial constraint and the essential excited-state behaviors of doped photosensitizer(4-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)ethyl)-1-methylquinolin-1-ium iodine,TPP).Through experimental investigation and theoretical calculations,we found that TPP tends to remain in the excited state for a shorter dwell time under weaker spatial constraints due to less restricted molecular motion in polyurethane(PU) nanofibers.Consequently,the singlet oxygen(^(1)O_(2)) generated from doped-TPP shows a 9.23-fold enhancement in PU than in the polyvinylchloride(PVC) matrix.Under light irradiation,the PU@TPP nanofiber can efficiently eliminate the coronavirus MHV-A59(≥99.9997%) at a 220,000-fold higher concentration than the infected space.Its antibacterial efficacy has also been demonstrated,with a killing rate of ≥99%.展开更多
Nowadays,infectious diseases persist as a global crisis by causing significant destruction to public health and the economic stability of countries worldwide.Especially bacterial infections remain a most severe concer...Nowadays,infectious diseases persist as a global crisis by causing significant destruction to public health and the economic stability of countries worldwide.Especially bacterial infections remain a most severe concern due to the prevalence and emergence of multi-drug resistance(MDR)and limitations with existing therapeutic options.Antibacterial photodynamic therapy(APDT)is a potential therapeutic modality that involves the systematic administration of photosensitizers(PSs),light,and molecular oxygen(O_(2))for coping with bacterial infections.Although the existing porphyrin and non-porphyrin PSs were effective in APDT,the poor solubility,limited efficacy against Gram-negative bacteria,and non-specific distribution hinder their clinical applications.Accordingly,to promote the efficiency of conventional PSs,various polymer-driven modification and function-alization strategies have been adopted to engineer multifunctional hybrid phototherapeutics.This review as-sesses recent advancements and state-of-the-art research in polymer-PSs hybrid materials developed for APDT applications.Further,the key research findings of the following aspects are considered in-depth with constructive discussions:i)PSs-integrated/functionalized polymeric composites through various molecular in-teractions;ii)PSs-deposited coatings on different substrates and devices to eliminate healthcare-associated in-fections;and iii)PSs-embedded films,scaffolds,and hydrogels for regenerative medicine applications.展开更多
The aim of this study was to evaluate the factors influencing the inactivation effect of intense pulsed light(IPL)on Aeromonas salmonicida grown on chicken meat and skin,and to further develop prediction models of ina...The aim of this study was to evaluate the factors influencing the inactivation effect of intense pulsed light(IPL)on Aeromonas salmonicida grown on chicken meat and skin,and to further develop prediction models of inactivation.In this work,chicken meat and skin inoculated with meat-borne A.salmonicida isolates were subjected to IPL treatments under different conditions.The results showed that IPL had obvious bactericidal effect in the chicken skin and thickness groups when the treatment voltage and time were 7 V combined with 5 s.In addition,the lethality curves of A.salmonicida were fitted under IPL conditions of 3.5-7.5 V.The comparison of statistical parameters revealed that the Weibull model could best fit the mortality curves and could accurately predict the mortality dynamic of A.salmonicida grown on chicken skin.And further a secondary model between the scale factor b and the treatment voltage in Weibull model was established using linear equations,which determined that the secondary model could accurately predict the inactivation of A.salmonicida.This study provides a theoretical basis for future prediction models of Aeromonas,and also provides new ideas for sterilization approaches of meat-borne Aeromonas.展开更多
Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppre...Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.展开更多
Photodynamic therapy(PDT)can take place in the presence of three elements:Light with an appropriate wavelength;a photosensitizer;and the presence of oxygen.This type of treatment is very effective overall against bact...Photodynamic therapy(PDT)can take place in the presence of three elements:Light with an appropriate wavelength;a photosensitizer;and the presence of oxygen.This type of treatment is very effective overall against bacterial,viral and mycotic cells.In the last 10 years many papers have been published on PDT with different types of photosensitizers(e.g.,methylene blue,toluidine blue,indocyanine green,curcumin-based photosensitizers),different wavelengths(e.g.,460 nm,630 nm,660 nm,810 nm)and various parameters(e.g.,power of the light,time of illumination,number of sessions).In the scientific literature all types of PDT seem very effective,even if it is difficult to find a standard protocol for each oral pathology.PDT could be an interesting way to treat some dangerous oral infections refractory to common pharmacological therapies,such as candidiasis from multidrug-resistant Candida spp.展开更多
Photodynamic therapy(PDT)is applied as a robust therapeutic option for tumor,which exhibits some advantages of unique selectivity and irreversible damage to tumor cells.Among which,photosensitizer(PS),appropriate lase...Photodynamic therapy(PDT)is applied as a robust therapeutic option for tumor,which exhibits some advantages of unique selectivity and irreversible damage to tumor cells.Among which,photosensitizer(PS),appropriate laser irradiation and oxygen(O_(2))are three essential components for PDT,but the hypoxic tumor microenvironment(TME)restricts the O_(2) supply in tumor tissues.Even worse,tumor metastasis and drug resistance frequently happen under hypoxic condition,which further deteriorate the antitumor effect of PDT.To enhance the PDT efficiency,critical attention has been received by relieving tumor hypoxia,and innovative strategies on this topic continue to emerge.Traditionally,the O_(2) supplement strategy is considered as a direct and effective strategy to relieve TME,whereas it is confronted with great challenges for continuous O_(2) supply.Recently,O_(2)-independent PDT provides a brand new strategy to enhance the antitumor efficiency,which can avoid the influence of TME.In addition,PDT can synergize with other antitumor strategies,such as chemotherapy,immunotherapy,photothermal therapy(PTT)and starvation therapy,to remedy the inadequate PDT effect under hypoxia conditions.In this paper,we summarized the latest progresses in the development of innovative strategies to improve PDT efficacy against hypoxic tumor,which were classified into O_(2)-dependent PDT,O_(2)-independent PDT and synergistic therapy.Furthermore,the advantages and deficiencies of various strategies were also discussed to envisage the prospects and challenges in future study.展开更多
Background:((1-triphenylaminebenzo[c][1,2,5]thiadiazole-4-yl)styryl)-1-methylpyridin methylpyridin-1-ium iodide salt(TBZPy)is a novel photosensitizer that displays excellent photodynamic properties.However,There are f...Background:((1-triphenylaminebenzo[c][1,2,5]thiadiazole-4-yl)styryl)-1-methylpyridin methylpyridin-1-ium iodide salt(TBZPy)is a novel photosensitizer that displays excellent photodynamic properties.However,There are few reports on the mechanism of action of the TBZPy photodynamic.Previous studies revealed that photodynamic therapy(PDT)could induce endoplasmic reticulum stress by acting on the endoplasmic reticulum.Therefore,in this study,we investigated the effects of endoplasmic reticulum stress induced by TBZPy-PDT in treating High-risk human papillomavirus(HR-HPV)infection and their underlying mechanisms.Methods:The human cervical cancer cell line HeLa(containing whole genome of HR-HPV18)was treated with TBZPy-PDT.Cell migration,invasion,and colony-forming ability were evaluated using wound-healing,Transwell invasion,and colonyforming assays,respectively.Through western blot analysis,we determined the level of expression of the PI3K/AKT and PERK/eIF2αpathway proteins and the proteins associated with calcium trafficking and apoptosis.The calcium levels in the cytoplasm were detected via flow cytometry.Results:The result shows that TBZPy-PDT could inhibite the migration,invasion,and colony forming ability of infected HeLa cells by downregulating the PI3K/AKT pathway in vitro.And we found that TBZPy-PDT induced endoplasmic reticulum stress-specific apoptosis via the PERK/eIF2αpathway.Moreover,TBZPy-PDT increased the levels of calcium and calmodulin,while decreasing the levels of endoplasmic reticulum calcium-binding proteins.Conclusions:TBZPy-PDT is effective on treating human papillomavirus-infected cells.Targeting the PI3K/AKT and PERK/eIF2αpathways and the endoplasmic reticulum stress process may help improve the effects of TBZPy-PDT for treating high-risk human papillomavirus infection.展开更多
Current antitumor monotherapy has many limitations,highlighting the need for novel synergistic anticancer strategies.Ferroptosis is an iron-dependent form of nonapoptotic cell death that plays a pivotal regulatory rol...Current antitumor monotherapy has many limitations,highlighting the need for novel synergistic anticancer strategies.Ferroptosis is an iron-dependent form of nonapoptotic cell death that plays a pivotal regulatory role in tumorigenesis and treatment.Photodynamic therapy(PDT)causes irreversible chemical damage to target lesions and is widely used in antitumor therapy.However,PDT’s effectiveness is usually hindered by several obstacles,such as hypoxia,excess glutathione(GSH),and tumor resistance.Ferroptosis improves the anticancer efficacy of PDT by increasing oxygen and reactive oxygen species(ROS)or reducing GSH levels,and PDT also enhances ferroptosis induction due to the ROS effect in the tumor microenvironment(TME).Strategies based on nanoparticles(NPs)can subtly exploit the potential synergy of ferroptosis and PDT.This review explores recent advances and current challenges in the landscape of the underlyingmechanisms regulating ferroptosis and PDT,as well as nano delivery system-mediated synergistic anticancer activity.These include polymers,biomimetic materials,metal organic frameworks(MOFs),inorganics,and carrier-free NPs.Finally,we highlight future perspectives of this novel emerging paradigm in targeted cancer therapies.展开更多
Port-wine stain(PWS)is a congenital capillary malformation that occurs in 0.3%–0.5%of newborns.The pulsed dye laser is the current gold standard treatment for PWS;however,its efficacy is poor.Photosensitizer photodyn...Port-wine stain(PWS)is a congenital capillary malformation that occurs in 0.3%–0.5%of newborns.The pulsed dye laser is the current gold standard treatment for PWS;however,its efficacy is poor.Photosensitizer photodynamic therapy(PDT)is considered a promising treatment for PWS.Here we provide a comprehensive overview of PDT.展开更多
基金supported by the Shenzhen Science and Technology Program (JSGG20200225151916021)the National Natural Science Foundation of China (U21A2097)+3 种基金Department of Science and Technology of Guangdong Province (2019ZT08Y191,2019QN01Y640)Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022B1212010003)Shenzhen Key Laboratory of Smart Healthcare Engineering (ZDSYS20200811144003009)Shenzhen Science and Technology Program (KQTD20190929172743294)。
文摘The critical factor of spatial constraint,provided by the external confinement(e.g.,matrix),is often overlooked during photodynamic inactivation,despite playing a crucial role in determining the molecular photophysical process and subsequent antipathogen performance.Here,as a proof-of-concept model,we employed two types of polymers with varying interaction energies with dopants to investigate the intrinsic relationship between spatial constraint and the essential excited-state behaviors of doped photosensitizer(4-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)ethyl)-1-methylquinolin-1-ium iodine,TPP).Through experimental investigation and theoretical calculations,we found that TPP tends to remain in the excited state for a shorter dwell time under weaker spatial constraints due to less restricted molecular motion in polyurethane(PU) nanofibers.Consequently,the singlet oxygen(^(1)O_(2)) generated from doped-TPP shows a 9.23-fold enhancement in PU than in the polyvinylchloride(PVC) matrix.Under light irradiation,the PU@TPP nanofiber can efficiently eliminate the coronavirus MHV-A59(≥99.9997%) at a 220,000-fold higher concentration than the infected space.Its antibacterial efficacy has also been demonstrated,with a killing rate of ≥99%.
基金National Natural Science Foundation of China(21504072,51741304 and 52073234)Natural Science Foundation of Chongqing(cstc2019jcyj-msxmX0363)+1 种基金Innovation Teams in Colleges and Universities of Chongqing(CXQT20005)innovation platform for Academicians of Hainan Province and Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices.
文摘Nowadays,infectious diseases persist as a global crisis by causing significant destruction to public health and the economic stability of countries worldwide.Especially bacterial infections remain a most severe concern due to the prevalence and emergence of multi-drug resistance(MDR)and limitations with existing therapeutic options.Antibacterial photodynamic therapy(APDT)is a potential therapeutic modality that involves the systematic administration of photosensitizers(PSs),light,and molecular oxygen(O_(2))for coping with bacterial infections.Although the existing porphyrin and non-porphyrin PSs were effective in APDT,the poor solubility,limited efficacy against Gram-negative bacteria,and non-specific distribution hinder their clinical applications.Accordingly,to promote the efficiency of conventional PSs,various polymer-driven modification and function-alization strategies have been adopted to engineer multifunctional hybrid phototherapeutics.This review as-sesses recent advancements and state-of-the-art research in polymer-PSs hybrid materials developed for APDT applications.Further,the key research findings of the following aspects are considered in-depth with constructive discussions:i)PSs-integrated/functionalized polymeric composites through various molecular in-teractions;ii)PSs-deposited coatings on different substrates and devices to eliminate healthcare-associated in-fections;and iii)PSs-embedded films,scaffolds,and hydrogels for regenerative medicine applications.
基金supported by projects funded by grants from the Natural Science Foundation of Jiangsu Province in China(BK20221515)the National Natural Science Foundation of China(32172266)the Changzhou Science and Technology Support Program(CE20222002)。
文摘The aim of this study was to evaluate the factors influencing the inactivation effect of intense pulsed light(IPL)on Aeromonas salmonicida grown on chicken meat and skin,and to further develop prediction models of inactivation.In this work,chicken meat and skin inoculated with meat-borne A.salmonicida isolates were subjected to IPL treatments under different conditions.The results showed that IPL had obvious bactericidal effect in the chicken skin and thickness groups when the treatment voltage and time were 7 V combined with 5 s.In addition,the lethality curves of A.salmonicida were fitted under IPL conditions of 3.5-7.5 V.The comparison of statistical parameters revealed that the Weibull model could best fit the mortality curves and could accurately predict the mortality dynamic of A.salmonicida grown on chicken skin.And further a secondary model between the scale factor b and the treatment voltage in Weibull model was established using linear equations,which determined that the secondary model could accurately predict the inactivation of A.salmonicida.This study provides a theoretical basis for future prediction models of Aeromonas,and also provides new ideas for sterilization approaches of meat-borne Aeromonas.
文摘Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.
文摘Photodynamic therapy(PDT)can take place in the presence of three elements:Light with an appropriate wavelength;a photosensitizer;and the presence of oxygen.This type of treatment is very effective overall against bacterial,viral and mycotic cells.In the last 10 years many papers have been published on PDT with different types of photosensitizers(e.g.,methylene blue,toluidine blue,indocyanine green,curcumin-based photosensitizers),different wavelengths(e.g.,460 nm,630 nm,660 nm,810 nm)and various parameters(e.g.,power of the light,time of illumination,number of sessions).In the scientific literature all types of PDT seem very effective,even if it is difficult to find a standard protocol for each oral pathology.PDT could be an interesting way to treat some dangerous oral infections refractory to common pharmacological therapies,such as candidiasis from multidrug-resistant Candida spp.
文摘Photodynamic therapy(PDT)is applied as a robust therapeutic option for tumor,which exhibits some advantages of unique selectivity and irreversible damage to tumor cells.Among which,photosensitizer(PS),appropriate laser irradiation and oxygen(O_(2))are three essential components for PDT,but the hypoxic tumor microenvironment(TME)restricts the O_(2) supply in tumor tissues.Even worse,tumor metastasis and drug resistance frequently happen under hypoxic condition,which further deteriorate the antitumor effect of PDT.To enhance the PDT efficiency,critical attention has been received by relieving tumor hypoxia,and innovative strategies on this topic continue to emerge.Traditionally,the O_(2) supplement strategy is considered as a direct and effective strategy to relieve TME,whereas it is confronted with great challenges for continuous O_(2) supply.Recently,O_(2)-independent PDT provides a brand new strategy to enhance the antitumor efficiency,which can avoid the influence of TME.In addition,PDT can synergize with other antitumor strategies,such as chemotherapy,immunotherapy,photothermal therapy(PTT)and starvation therapy,to remedy the inadequate PDT effect under hypoxia conditions.In this paper,we summarized the latest progresses in the development of innovative strategies to improve PDT efficacy against hypoxic tumor,which were classified into O_(2)-dependent PDT,O_(2)-independent PDT and synergistic therapy.Furthermore,the advantages and deficiencies of various strategies were also discussed to envisage the prospects and challenges in future study.
基金supported by the Natural Science Foundation of Gansu Province(22JR5RA496,22JR5RA955)Talent Innovation and Entrepreneurship Project of Lanzhou City(2022-RC-49)+4 种基金Talent Innovation and Entrepreneurship Project of Chengguan District(2022-rc-7)Foundation of Lanzhou University Second Hospital(CYXZ2022-22)Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital(CY2021-QN-A02)Fundamental Research Funds for the Central Universities(lzujbky-2022-50)Project of Gansu Province Health Commission(GSWSKY2022-02)Innovation Fund for Colleges and Universities(2021B-046).
文摘Background:((1-triphenylaminebenzo[c][1,2,5]thiadiazole-4-yl)styryl)-1-methylpyridin methylpyridin-1-ium iodide salt(TBZPy)is a novel photosensitizer that displays excellent photodynamic properties.However,There are few reports on the mechanism of action of the TBZPy photodynamic.Previous studies revealed that photodynamic therapy(PDT)could induce endoplasmic reticulum stress by acting on the endoplasmic reticulum.Therefore,in this study,we investigated the effects of endoplasmic reticulum stress induced by TBZPy-PDT in treating High-risk human papillomavirus(HR-HPV)infection and their underlying mechanisms.Methods:The human cervical cancer cell line HeLa(containing whole genome of HR-HPV18)was treated with TBZPy-PDT.Cell migration,invasion,and colony-forming ability were evaluated using wound-healing,Transwell invasion,and colonyforming assays,respectively.Through western blot analysis,we determined the level of expression of the PI3K/AKT and PERK/eIF2αpathway proteins and the proteins associated with calcium trafficking and apoptosis.The calcium levels in the cytoplasm were detected via flow cytometry.Results:The result shows that TBZPy-PDT could inhibite the migration,invasion,and colony forming ability of infected HeLa cells by downregulating the PI3K/AKT pathway in vitro.And we found that TBZPy-PDT induced endoplasmic reticulum stress-specific apoptosis via the PERK/eIF2αpathway.Moreover,TBZPy-PDT increased the levels of calcium and calmodulin,while decreasing the levels of endoplasmic reticulum calcium-binding proteins.Conclusions:TBZPy-PDT is effective on treating human papillomavirus-infected cells.Targeting the PI3K/AKT and PERK/eIF2αpathways and the endoplasmic reticulum stress process may help improve the effects of TBZPy-PDT for treating high-risk human papillomavirus infection.
基金supported by China Medical University’s High-level Talents Research Start-up Fund(1210619010)Double First-Class Scientific Research Fund(3110210603).
文摘Current antitumor monotherapy has many limitations,highlighting the need for novel synergistic anticancer strategies.Ferroptosis is an iron-dependent form of nonapoptotic cell death that plays a pivotal regulatory role in tumorigenesis and treatment.Photodynamic therapy(PDT)causes irreversible chemical damage to target lesions and is widely used in antitumor therapy.However,PDT’s effectiveness is usually hindered by several obstacles,such as hypoxia,excess glutathione(GSH),and tumor resistance.Ferroptosis improves the anticancer efficacy of PDT by increasing oxygen and reactive oxygen species(ROS)or reducing GSH levels,and PDT also enhances ferroptosis induction due to the ROS effect in the tumor microenvironment(TME).Strategies based on nanoparticles(NPs)can subtly exploit the potential synergy of ferroptosis and PDT.This review explores recent advances and current challenges in the landscape of the underlyingmechanisms regulating ferroptosis and PDT,as well as nano delivery system-mediated synergistic anticancer activity.These include polymers,biomimetic materials,metal organic frameworks(MOFs),inorganics,and carrier-free NPs.Finally,we highlight future perspectives of this novel emerging paradigm in targeted cancer therapies.
基金the National Natural Science Foundation of China(grant no.81971847)Interdisciplinary Program of Shanghai Jiao Tong University(grant no.YG2019QNB10)+1 种基金Shanghai Municipal Key Clinical Specialty(grant no.shslczdzk00901)Shanghai Municipal Commission of Health and Family Planning(grant no.202240150)。
文摘Port-wine stain(PWS)is a congenital capillary malformation that occurs in 0.3%–0.5%of newborns.The pulsed dye laser is the current gold standard treatment for PWS;however,its efficacy is poor.Photosensitizer photodynamic therapy(PDT)is considered a promising treatment for PWS.Here we provide a comprehensive overview of PDT.
