The internal electric field(IEF)is key in speeding up the separation and transfer of photogenerated carriers,which boosts the production of reactive oxygen species(ROS).In this study,we present a novel silver iodide/N...The internal electric field(IEF)is key in speeding up the separation and transfer of photogenerated carriers,which boosts the production of reactive oxygen species(ROS).In this study,we present a novel silver iodide/N-rich carbon nitride(AgI/C_(3)N_(5))heterojunction catalyst with an IEF directed from AgI to C_(3)N_(5).We confirmed this IEF using density functional theory(DFT)calculations and various characterization methods.This IEF induces and reinforces the Type II transfer pathway for carrier separation and transfer,significantly increasing the production of ROS,particularly singlet oxygen(1O_(2)).As a result,the AgI/C_(3)N_(5)catalysts achieve 10.1 times the disinfection efficiency of C_(3)N_(5)and 5.6 times that of AgI,under one-min reaction time,107 CFU/mL of E.coli,visible light,and room temperature.It also outperforms most other AgI and carbon nitride-based heterojunction photocatalysts.Notably,the photogenerated holes(h+)selectively oxidize superoxide radicals(·O_(2)^(-))to 1O_(2)due to favorable energy alignment,minimizing O_(2)reduction effects and enhancing photocorrosion resistance,as demonstrated in five consecutive cycling experiments.In addition,the actual water disinfection tests confirmed its practical application potential.This work highlights the AgI/C_(3)N_(5)heterojunction catalyst’s promise as an efficient disinfection agent and sheds light on the photocatalytic disinfection mechanism.展开更多
Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer,their inefficient therapeutic outcomes,serious adverse effects,and high cost of mass production remai...Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer,their inefficient therapeutic outcomes,serious adverse effects,and high cost of mass production remain crucial challenges.Herein,we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers(TFENs).These nanovehicles had desirable particle sizes(131 nm),exosome-like morphology,and negative zeta potentials.Furthermore,TFENs were found to contain large amounts of polyphenols,flavonoids,functional proteins,and lipids.Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species(ROS)amplification.The increased intracellular ROS amounts could not only trigger mitochondrial damage,but also arrest cell cycle,resulting in the in vitro anti-proliferation,anti-migration,and anti-invasion activities against breast cancer cells.Further mice investigations demonstrated that TFENs after intravenous(i.v.)injection or oral administration could accumulate in breast tumors and lung metastatic sites,inhibit the growth and metastasis of breast cancer,and modulate gut microbiota.This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v.and oral routes.展开更多
Vanadium compounds show potential in diabetes and cancer treatment, although the toxicity remains a great concern. Previous studies have shown that vanadium-induced oxidative stress affecting mitochondrial function is...Vanadium compounds show potential in diabetes and cancer treatment, although the toxicity remains a great concern. Previous studies have shown that vanadium-induced oxidative stress affecting mitochondrial function is intensively responsible for the toxicity. In this work, we investigated the effects of the vanadium compounds sodium metavanadate （NaVO3） and vanadyl acetylacetonate （VO（acac）2） on mitochondrial ROS generation and respiratory complex activities. The experimental results showed that vanadium compounds affected the ROS generation and complex activities in different patterns depending on the chemical species. NaVO3 inhibited mitochondrial complexes Ⅰ and Ⅱ activities and stimulated ROS generation at low concentration range; while VO（acac）2 promoted complex Ⅱ activity but resulted in electron leakage from the complex Ⅰ-involved pathway. The present results provide new evidence for understanding the toxicity of antidiabetic vanadium compounds.展开更多
Fluorescence imaging-guided photodynamic therapy holds great promise for application in precise cancer diagnosis and treatment,which has motivated high requirements for phototheranostic agents.However,current photosen...Fluorescence imaging-guided photodynamic therapy holds great promise for application in precise cancer diagnosis and treatment,which has motivated high requirements for phototheranostic agents.However,current photosensitizers(PSs)generally face limitations such as short emission wavelength and inadequate reactive oxygen species(ROS)production.Aggregation-caused quenching issue also hinders the phototheranostic efficiency of PSs.Herein,theπ-bridge modulation strategy is proposed to construct ionic PSs with enhanced bioimaging and therapeutic outcomes.Two donor-π-acceptor(D-π-A)molecules TPCPY and TFCPY were obtained by incorporating phenyl and furan units asπ-bridge,respectively.Both PSs feature aggregation-induced near-infrared emission.Under light irradiation,TPCPY and TFCPY can produce both typeⅠandⅡROS.Introducing furan ring in TFCPY enhances the ROS generation capacity by typeⅠphotosensitization process,which is consistent with the reduced energy gap between singlet and triplet states from theoretical calculation.Furthermore,TFCPY can achieve quick cellular uptake,accumulate in mitochondria,and then efficiently kill cancer cells,which is superior to TPCPY.Consequently,TFCPY exhibited good antitumor outcomes and excellent in vivo fluorescence imaging ability.This work provides an efficient molecular engineering of introducing heterocycles into the D-π-A skeleton to develop high-performance PSs with both typeⅠandⅡROS generation.展开更多
Photodynamic therapy(PDT)brings new hope for the treatment of breast cancer due to few side effects and highly effective cell killing;however,the low bioavailability of traditional photosensitizers(PSs)and their depen...Photodynamic therapy(PDT)brings new hope for the treatment of breast cancer due to few side effects and highly effective cell killing;however,the low bioavailability of traditional photosensitizers(PSs)and their dependence on oxygen severely limits their application.Aggregation-induced emission(AIE)PSs can dramatically facilitate the photosensitization effect,which can have positive impacts on tumor PDT.To-date,most AIE PSs lack tumor targeting capability and possess poor cell delivery,resulting in their use in large quantities that are harmful to healthy tissues.In this study,a series of AIE PSs based on pyridinium-substituted triphenylamine salts(TTPAs 1-6)with different alkyl chain lengths are synthesized.Results reveal that TTPAs 1-6 promote the generation of type I and II ROS,including·OH and 1O_(2).In particular,the membrane permeability and targeting of TTPAs 4-6 bearing C8-C10 side-chains are higher than TTPAs 1-3 bearing shorter alkyl chains.Additionally,they can assemble with albumin,thereby forming nanoparticles(TTPA 4-6 NPs)in situ in blood,which significantly facilitates mitochondrial-targeting and strong ROS generation ability.Moreover,the TTPA 4-6 NPs are pH-responsive,allowing for increased accumulation or endocytosis of the tumor and enhancing the imaging or therapeutic effect.Therefore,the in vivo distributions of TTPA 4-6 NPs are visually enriched in tumor sites and exhibited excellent PDT efficacy.This work demonstrates a novel strategy for AIE PDT and has the potential to play an essential role in clinical applications using nano-delivery systems.展开更多
ABSTRACT:Although radiotherapy(RT)can induce immunogenic cell death(ICD),the endogenous resistance of tumor cells to X-rays and the immunosuppressive microenvironment has suppressed its therapeutic effect,which can ea...ABSTRACT:Although radiotherapy(RT)can induce immunogenic cell death(ICD),the endogenous resistance of tumor cells to X-rays and the immunosuppressive microenvironment has suppressed its therapeutic effect,which can easily lead to tumor recurrence and metastasis after RT.Herein,we prepared a glutathione(GSH)-responsive system called AHD,by loading Aurora-A inhibitor alisertib(Ali)and iron protoporphyrin Ⅸ chloride(Hemin),for X-raytriggered continuous reactive oxygen species(ROS)generation to sensitize breast cancer senescence immunotherapy.AHD accumulates at the tumor tissue through the enhanced permeability and retention(EPR)effect,shows high specificity for the tumor microenvironment with overexpressed GSH,and rapidly releases Ali and Hemin.Under external X-ray irradiation,tumor cells produce H_(2)O_(2),and AHD activates Hemin to catalyze the chemical kinetics process of H_(2)O_(2),continuously generating hydroxyl radicals(·OH).Meanwhile,AHD can also induce tumor cell senescence by up-regulating P21 and P16 expressions.In vitro and in vivo experimental results show that the cascade ROS generation induced by the AHD system can trigger extensive ICD in tumor cells,alleviate the immunosuppressive microenvironment after RT,activate the anti-tumor immune ability of CD8^(+)T cells.Therefore,AHD can be used as a tumor immunomodulator to enhance radioimmunotherapy and has great potential for clinical translation.展开更多
On March 27,“Zhong Yuan Hai Yun Zhi Xing”,a 300passenger ro-ro ship built by CSSC Guangzhou Shipbuilding International Co.,Ltd.(GSI),a subsidiary of China State Shipbuilding Corporation,for Xiamen Mintai Ferry Co.,L...On March 27,“Zhong Yuan Hai Yun Zhi Xing”,a 300passenger ro-ro ship built by CSSC Guangzhou Shipbuilding International Co.,Ltd.(GSI),a subsidiary of China State Shipbuilding Corporation,for Xiamen Mintai Ferry Co.,Ltd.under COSCO Shipping,was christened and delivered.展开更多
Three water-soluble Mn(III)-porphyrin complexes with cationic pyridyl side groups bearing COOH-or OH-terminated carbon chains in the meta or para positions have been synthesized as probes for both magnetic resonance i...Three water-soluble Mn(III)-porphyrin complexes with cationic pyridyl side groups bearing COOH-or OH-terminated carbon chains in the meta or para positions have been synthesized as probes for both magnetic resonance imaging(MRI)and photodynamic therapy(PDT).The complexes Mn-1,Mn-2,and Mn-3 are highly water-soluble,and their relaxivities range between 10 and 15 mM^(-1) s^(-1),at 20-80 MHz and 298 K,2-3 times higher than that of commercial Gd(III)-based agents.The complexes containing carboxylate(Mn-2)or alcoholic(Mn-3)side chains in the para position are endowed with higher relaxivities and have also shown efficient photoinduced DNA cleavage and singlet oxygen(^(1)O_(2))generation.Mn-3 with stronger photoinduced DNA cleavage has also revealed stabilizing and binding activities for G4 DNA,at a similar level as the known G4 binder Mn-TMPyP4.Nevertheless,the G4-binding activity of Mn-3 was nonspecific.Preliminary tests evidenced photocytotoxicity of Mn-3 on HeLa cells without a significant effect in the absence of light.Altogether,these results underline the potential of such water-soluble Mn(III)-porphyrins for the development of multimodal approaches combining MRI and PDT.展开更多
Phototherapy has emerged as a promising modality in cancer treatment,garnering considerable attention for its minimal side effects,exceptional spatial selectivity,and optimal preservation of normal tissue function.Thi...Phototherapy has emerged as a promising modality in cancer treatment,garnering considerable attention for its minimal side effects,exceptional spatial selectivity,and optimal preservation of normal tissue function.This innovative approach primarily encompasses three distinct paradigms:Photodynamic Therapy(PDT),Photothermal Therapy(PTT),and Photoimmunotherapy(PIT).Each of these modalities exerts its antitumor effects through unique mechanisms—specifically,the generation of reactive oxygen species(ROS),heat,and immune responses,respectively.However,significant challenges impede the advancement and clinical application of phototherapy.These include inadequate ROS production rates,subpar photothermal conversion efficiency,difficulties in tumor targeting,and unfavorable physicochemical properties inherent to traditional phototherapeutic agents(PTs).Additionally,the hypoxic microenvironment typical of tumors complicates therapeutic efficacy due to limited agent penetration in deep-seated lesions.To address these limitations,ongoing research is fervently exploring innovative solutions.The unique advantages offered by nano-PTs and nanocarrier systems aim to enhance traditional approaches’effectiveness.Strategies such as generating oxygen in situ within tumors or inhibiting mitochondrial respiration while targeting the HIF-1αpathway may alleviate tumor hypoxia.Moreover,utilizing self-luminescent materials,near-infrared excitation sources,non-photoactivated sensitizers,and wireless light delivery systems can improve light penetration.Furthermore,integrating immunoadjuvants and modulating immunosuppressive cell populations while deploying immune checkpoint inhibitors holds promise for enhancing immunogenic cell death through PIT.This review seeks to elucidate the fundamental principles and biological implications of phototherapy while discussing dominant mechanisms and advanced strategies designed to overcome existing challenges—ultimately illuminating pathways for future research aimed at amplifying this intervention’s therapeutic efficacy.展开更多
Nanoparticles(NPs)exhibit unique physicochemical properties that render them valuable for applications in several fields,such as drug delivery and diagnostics.However,these properties can lead to adverse biological re...Nanoparticles(NPs)exhibit unique physicochemical properties that render them valuable for applications in several fields,such as drug delivery and diagnostics.However,these properties can lead to adverse biological reactions,including cell toxicity.The mechanisms of NP-induced cytotoxicity involve complex pathways,including the generation of oxidative stress,reactive oxygen species(ROS),protein corona formation,and interactions with cell-uptake processes such as endocytosis and phagocytosis.This review discusses the in vivo and in vitro assays that help assess NP toxicity,covering cell viability,ROS generation,genotoxicity,and apoptosis.It highlights the importance of selecting appropriate methods to accurately evaluate the risks posed by NPs.The implications of these findings underscore the need for carefully formulating NP design to mitigate cytotoxic effects,ensuring safe and effective medical and industrial applications.展开更多
Plastic products widespread in natural water can be broken into smaller-sized microplastics(MPs,<5 mm)under light irradiation,thermal degradation and biodegradation,posing a serious threat to aquatic ecosystems and...Plastic products widespread in natural water can be broken into smaller-sized microplastics(MPs,<5 mm)under light irradiation,thermal degradation and biodegradation,posing a serious threat to aquatic ecosystems and human health.This perspective concludes that MPs can generate reactive oxygen species(ROS)through initiation,propagation and termination steps,which can attack the polymer resulting in the photoaging and breakdown of C–C and C–H bonds under ultraviolet(UV)irradiation.Free radical generation and weathering degree of MPs depend on their physicochemical properties and environmental conditions.In general,UV irradiation and co-existed MPs can significantly accelerate MP photoaging.With plentiful chromophores carbonyl,carboxyl and benzene rings,Dissolved organic matter(DOM)mainly absorbs photons(300–500 nm)and generates hydrated electrons,^(3)DOM^(*) and ROS,which may affect MP photoaging.However,whether DOM may transfer the electron and energy to MPs under UV irradiation,affect ROS generation of MPs and their photoaging pathway are inadequately studied.More studies are needed to elucidate MP photoaging pathways and mechanisms,consider the influence of stabilization capacity,photosensitization and photoionization of DOM as well as their competitive light absorption with MPs,which provides valuable insights into the environmental behavior and ecological risk of MPs in natural water.展开更多
Ferroptosis is a form of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation and lethal reactive oxygen species(ROS).To date,misregulated ferroptosis has been implicated in several ...Ferroptosis is a form of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation and lethal reactive oxygen species(ROS).To date,misregulated ferroptosis has been implicated in several types of cancers,and ferroptosis inducers can be used to promote ferroptosis in tumor cells and play an anti-tumor role.However,the specificity and efficacy of ferroptosis inducers remain unsatisfactory.Here,a new mitochondria-targeted photosensitizer(PS)with aggregation-induced emission(AIE)characteristic named TCSVP was designed,which efficiently generates ROS in mitochondria after light exposure.TCSVP administration significantly sensitizes tumor cells to ferroptosis inducer(RSL3)-mediated cell death by specifically and light-dependently triggering a moderate ROS generation in vitro and in vivo.Mechanically,the expression levels of ferroptosis related proteins Acyl-CoA synthetase long-chain family member 4(FACL4/ACSL4)and cyclooxygenase-2(COX2)were increased in TCSVP/RSL3-treated cells after light exposure,coupled with decreased Glutathione peroxidase 4(GPX4)activity and excessive malondialdehyde(MDA)accumulation.This study declared that light-induced moderate ROS generation within mitochondria in cancer cells by AIE-PS can be used to enhance the specificity and efficacy of ferroptosis inducers,bringing a new synergistic strategy for tumor intervention.展开更多
The present study describes the development and evaluation of a novel biocompatible dendrimer-based nano drug delivery system which is readily soluble in water prepared by condensing Phloroglucinol and Succinic Acid(P...The present study describes the development and evaluation of a novel biocompatible dendrimer-based nano drug delivery system which is readily soluble in water prepared by condensing Phloroglucinol and Succinic Acid(PGSA)and could efficiently encapsulate a well known hydrophobic photodynamic therapy(PDT)agent,protoporphyrin IX(PpIX).The(dark and photo)cytotoxicity of the PGSA-PpIX(dendrimer-drug)formulation towards Dalton Lymphoma Ascites(DLA)cancer cell lines upon visible light treatment is reported and evaluated the cytotoxic Reactive Oxygen Species(ROS)generation efficiency of the Protoporphyrin IX in free and dendrimer encapsulated forms.The in vitro toxicity demonstrated by PpIX loaded PGSA dendrimer nanoformulation,on DLA cells reveals that this novel PGSA nanocarrier reduces the toxic nature of PpIX when compared to free PpIX without light treatment which satisfy the aim of our study.On the other hand,treatment of DLA cells with PGSA dendrimer formulation in combination with light resulted in significant enhancement in therapeutic efficacy of the PDT agent,PpIX.展开更多
Objectives:Pesticide toxicity has become one of the major environmental menaces affecting all types of life forms of the ecosystem.Pesticides get washed off from agricultural fields into nearby water bodies and enter ...Objectives:Pesticide toxicity has become one of the major environmental menaces affecting all types of life forms of the ecosystem.Pesticides get washed off from agricultural fields into nearby water bodies and enter the aquatic organisms.Their bio-accumulated form finally reaches the human race,through consumption of pesticide infested aquatic animals,causing several physiological dysfunctions.Hence it becomes necessary to find a therapeutic cure/a preventive measure to stop the health hazard issues of pesticide.With this projection a search for a phyto-based-product was made whose primary objective would be to lower the pesticidal toxicity in fish and simultaneously in the human race.Methods:In this study we tried to check whether the phyto-chemical,Chlorophyllin(CHL),known for its anti-genotoxic,anti-oxidant activities,could render any kind of protection against Cypermethrin(CM)induced-toxicity in fish model and mammalian cell line L6.Both the model L6 and fish were pre-treated with CHL prior to exposure of CM.Different scientific parameters like%cellular cytotoxicity,reactive oxygen species(ROS)generation,nuclear condensation,etc were checked to validate the possibility of CHL in protecting CM-induced toxicity.Results:The overall results revealed that pre-treatment with CHL could restrict the ROS generation leading to modulation in associated cytokine proteins expression NFkβand IFNγ.Further,CHL lowered nuclear condensation and elevated expression of DNA repair proteins p53 and PARP,showing a kind of pre-activation of signalling cascades for overall protection against the severity of pesticidal toxicity.Conclusion:Thus,this phyto-based preventive approach would possibly solve many areas of human health issues related to pesticide toxicity in future.展开更多
Construction of multifunctional stimuli-responsive nanotherapeutics enabling improved intratumoral penetration of therapeutics and reversal of multiple-drug resistance(MDR)is potent to achieve effective cancer treatme...Construction of multifunctional stimuli-responsive nanotherapeutics enabling improved intratumoral penetration of therapeutics and reversal of multiple-drug resistance(MDR)is potent to achieve effective cancer treatment.Herein,we report a general method to synthesize pH-dissociable calcium carbonate(CaCO_(3))hollow nanoparticles with amorphous CaCO_(3)as the template,gallic acid(GA)as the organic ligand,and ferrous ions as the metallic center via a one-pot coordination reaction.The obtained GA–Fe@CaCO_(3)exhibits high loading efficiencies to both oxidized cisplatin prodrug and doxorubicin,yielding drug loaded GA-Fe@CaCO_(3)nanotherapeutics featured in pH-responsive size shrinkage,drug release,and Fenton catalytic activity.Compared to nonresponsive GA-Fe@silica nanoparticles prepared with silica nanoparticles as the template,such GA-Fe@CaCO_(3)confers significantly improved intratumoral penetration capacity.Moreover,both types of drug-loaded GA–Fe@CaCO_(3)nanotherapeutics exhibit synergistic therapeutic efficacies to corresponding MDR cancer cells because of the GA–Fe mediated intracellular oxidative stress amplification that could reduce the efflux of engulfed drugs by impairing the mitochondrial-mediated production of adenosine triphosphate(ATP).As a result,it is found that the doxorubicin loaded GA-Fe@CaCO_(3)exhibits superior therapeutic effect towards doxorubicin-resistant 4T1 breast tumors via combined chemodynamic and chemo-therapies.This work highlights the preparation of pH-dissociable CaCO_(3)-based nanotherapeutics to enable effective tumor penetration for enhanced treatment of drug-resistant tumors.展开更多
基金supported by National Natural Science Foundation of China(Grant No.52300218 and 22476066)Yunnan Fundamental Research Projects(Grant No.202401CF070197).
文摘The internal electric field(IEF)is key in speeding up the separation and transfer of photogenerated carriers,which boosts the production of reactive oxygen species(ROS).In this study,we present a novel silver iodide/N-rich carbon nitride(AgI/C_(3)N_(5))heterojunction catalyst with an IEF directed from AgI to C_(3)N_(5).We confirmed this IEF using density functional theory(DFT)calculations and various characterization methods.This IEF induces and reinforces the Type II transfer pathway for carrier separation and transfer,significantly increasing the production of ROS,particularly singlet oxygen(1O_(2)).As a result,the AgI/C_(3)N_(5)catalysts achieve 10.1 times the disinfection efficiency of C_(3)N_(5)and 5.6 times that of AgI,under one-min reaction time,107 CFU/mL of E.coli,visible light,and room temperature.It also outperforms most other AgI and carbon nitride-based heterojunction photocatalysts.Notably,the photogenerated holes(h+)selectively oxidize superoxide radicals(·O_(2)^(-))to 1O_(2)due to favorable energy alignment,minimizing O_(2)reduction effects and enhancing photocorrosion resistance,as demonstrated in five consecutive cycling experiments.In addition,the actual water disinfection tests confirmed its practical application potential.This work highlights the AgI/C_(3)N_(5)heterojunction catalyst’s promise as an efficient disinfection agent and sheds light on the photocatalytic disinfection mechanism.
基金supported by the National Natural Science Foundation of China(82072060 and 81571807,China)the Fundamental Research Funds for the Central Universities(XDJK2019TY002 and 2020CDJQY-A041,China)+1 种基金the Natural Science Foundation Project of Chongqing(cstc2020jcyjmsxm X0292,China)the Venture&Innovation Support Program for Chongqing Overseas Returnees(cx2018029,China)。
文摘Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer,their inefficient therapeutic outcomes,serious adverse effects,and high cost of mass production remain crucial challenges.Herein,we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers(TFENs).These nanovehicles had desirable particle sizes(131 nm),exosome-like morphology,and negative zeta potentials.Furthermore,TFENs were found to contain large amounts of polyphenols,flavonoids,functional proteins,and lipids.Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species(ROS)amplification.The increased intracellular ROS amounts could not only trigger mitochondrial damage,but also arrest cell cycle,resulting in the in vitro anti-proliferation,anti-migration,and anti-invasion activities against breast cancer cells.Further mice investigations demonstrated that TFENs after intravenous(i.v.)injection or oral administration could accumulate in breast tumors and lung metastatic sites,inhibit the growth and metastasis of breast cancer,and modulate gut microbiota.This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v.and oral routes.
基金National Natural Science Foundation of China (Grant No.20671008/20971008)
文摘Vanadium compounds show potential in diabetes and cancer treatment, although the toxicity remains a great concern. Previous studies have shown that vanadium-induced oxidative stress affecting mitochondrial function is intensively responsible for the toxicity. In this work, we investigated the effects of the vanadium compounds sodium metavanadate （NaVO3） and vanadyl acetylacetonate （VO（acac）2） on mitochondrial ROS generation and respiratory complex activities. The experimental results showed that vanadium compounds affected the ROS generation and complex activities in different patterns depending on the chemical species. NaVO3 inhibited mitochondrial complexes Ⅰ and Ⅱ activities and stimulated ROS generation at low concentration range; while VO（acac）2 promoted complex Ⅱ activity but resulted in electron leakage from the complex Ⅰ-involved pathway. The present results provide new evidence for understanding the toxicity of antidiabetic vanadium compounds.
基金supported by the funding from Natural Science Foundation of Jilin Province(No.20220101191JC)National Natural Science Foundation of China(No.22175033)the 13th Five-Year Program for Science and Technology of Education Department of Jilin Province(No.JJKH20230800KJ)。
文摘Fluorescence imaging-guided photodynamic therapy holds great promise for application in precise cancer diagnosis and treatment,which has motivated high requirements for phototheranostic agents.However,current photosensitizers(PSs)generally face limitations such as short emission wavelength and inadequate reactive oxygen species(ROS)production.Aggregation-caused quenching issue also hinders the phototheranostic efficiency of PSs.Herein,theπ-bridge modulation strategy is proposed to construct ionic PSs with enhanced bioimaging and therapeutic outcomes.Two donor-π-acceptor(D-π-A)molecules TPCPY and TFCPY were obtained by incorporating phenyl and furan units asπ-bridge,respectively.Both PSs feature aggregation-induced near-infrared emission.Under light irradiation,TPCPY and TFCPY can produce both typeⅠandⅡROS.Introducing furan ring in TFCPY enhances the ROS generation capacity by typeⅠphotosensitization process,which is consistent with the reduced energy gap between singlet and triplet states from theoretical calculation.Furthermore,TFCPY can achieve quick cellular uptake,accumulate in mitochondria,and then efficiently kill cancer cells,which is superior to TPCPY.Consequently,TFCPY exhibited good antitumor outcomes and excellent in vivo fluorescence imaging ability.This work provides an efficient molecular engineering of introducing heterocycles into the D-π-A skeleton to develop high-performance PSs with both typeⅠandⅡROS generation.
基金supported by the National Natural Science Foundation of China (81860543,32360237)Guizhou Provincial Science and Technology Projects (ZK[2023]+4 种基金Key Project 041,ZK[2021]076,[2019]2792 and[2018]5779-14)Guizhou Provincial Department of Education Foundation (KY[2022]229)Cultivation program of the Affiliated Hospital of Guizhou Medical University (gyfynsfc-2022-39)Cultivation program of the Guizhou Medical University (20NSP012)CR thanks the University of Hull for support
文摘Photodynamic therapy(PDT)brings new hope for the treatment of breast cancer due to few side effects and highly effective cell killing;however,the low bioavailability of traditional photosensitizers(PSs)and their dependence on oxygen severely limits their application.Aggregation-induced emission(AIE)PSs can dramatically facilitate the photosensitization effect,which can have positive impacts on tumor PDT.To-date,most AIE PSs lack tumor targeting capability and possess poor cell delivery,resulting in their use in large quantities that are harmful to healthy tissues.In this study,a series of AIE PSs based on pyridinium-substituted triphenylamine salts(TTPAs 1-6)with different alkyl chain lengths are synthesized.Results reveal that TTPAs 1-6 promote the generation of type I and II ROS,including·OH and 1O_(2).In particular,the membrane permeability and targeting of TTPAs 4-6 bearing C8-C10 side-chains are higher than TTPAs 1-3 bearing shorter alkyl chains.Additionally,they can assemble with albumin,thereby forming nanoparticles(TTPA 4-6 NPs)in situ in blood,which significantly facilitates mitochondrial-targeting and strong ROS generation ability.Moreover,the TTPA 4-6 NPs are pH-responsive,allowing for increased accumulation or endocytosis of the tumor and enhancing the imaging or therapeutic effect.Therefore,the in vivo distributions of TTPA 4-6 NPs are visually enriched in tumor sites and exhibited excellent PDT efficacy.This work demonstrates a novel strategy for AIE PDT and has the potential to play an essential role in clinical applications using nano-delivery systems.
基金financial support from the Key Laboratory of Birth Defects and Stem Cell Biobank of Guangxi(No.GXWCHZDKF-2023-09).
文摘ABSTRACT:Although radiotherapy(RT)can induce immunogenic cell death(ICD),the endogenous resistance of tumor cells to X-rays and the immunosuppressive microenvironment has suppressed its therapeutic effect,which can easily lead to tumor recurrence and metastasis after RT.Herein,we prepared a glutathione(GSH)-responsive system called AHD,by loading Aurora-A inhibitor alisertib(Ali)and iron protoporphyrin Ⅸ chloride(Hemin),for X-raytriggered continuous reactive oxygen species(ROS)generation to sensitize breast cancer senescence immunotherapy.AHD accumulates at the tumor tissue through the enhanced permeability and retention(EPR)effect,shows high specificity for the tumor microenvironment with overexpressed GSH,and rapidly releases Ali and Hemin.Under external X-ray irradiation,tumor cells produce H_(2)O_(2),and AHD activates Hemin to catalyze the chemical kinetics process of H_(2)O_(2),continuously generating hydroxyl radicals(·OH).Meanwhile,AHD can also induce tumor cell senescence by up-regulating P21 and P16 expressions.In vitro and in vivo experimental results show that the cascade ROS generation induced by the AHD system can trigger extensive ICD in tumor cells,alleviate the immunosuppressive microenvironment after RT,activate the anti-tumor immune ability of CD8^(+)T cells.Therefore,AHD can be used as a tumor immunomodulator to enhance radioimmunotherapy and has great potential for clinical translation.
文摘On March 27,“Zhong Yuan Hai Yun Zhi Xing”,a 300passenger ro-ro ship built by CSSC Guangzhou Shipbuilding International Co.,Ltd.(GSI),a subsidiary of China State Shipbuilding Corporation,for Xiamen Mintai Ferry Co.,Ltd.under COSCO Shipping,was christened and delivered.
基金supported in part by SNF Strategic Japanese-Swiss Science and Technology Program(IZLJZ2_183660,YY)JSPS,under the Joint Research Program implemented in association with SNF(20191508,H.M.and N.Y.-S),SNF Project Funding(205321_173018,Y.Y.)+4 种基金ETH Research Grants(ETH-21_15-2ETH-36_20-2,Y.Y.)JSPS KAKENHI(Grant-in-Aid for Scientific Research[A],6251004,H.M.Grants-in-Aid for Scientific Research on Innovative Areas,21H00264,22H04707,H.M.Grant-in-Aid for Scientific Research[C],15K07164,N.Y.-S).
文摘Three water-soluble Mn(III)-porphyrin complexes with cationic pyridyl side groups bearing COOH-or OH-terminated carbon chains in the meta or para positions have been synthesized as probes for both magnetic resonance imaging(MRI)and photodynamic therapy(PDT).The complexes Mn-1,Mn-2,and Mn-3 are highly water-soluble,and their relaxivities range between 10 and 15 mM^(-1) s^(-1),at 20-80 MHz and 298 K,2-3 times higher than that of commercial Gd(III)-based agents.The complexes containing carboxylate(Mn-2)or alcoholic(Mn-3)side chains in the para position are endowed with higher relaxivities and have also shown efficient photoinduced DNA cleavage and singlet oxygen(^(1)O_(2))generation.Mn-3 with stronger photoinduced DNA cleavage has also revealed stabilizing and binding activities for G4 DNA,at a similar level as the known G4 binder Mn-TMPyP4.Nevertheless,the G4-binding activity of Mn-3 was nonspecific.Preliminary tests evidenced photocytotoxicity of Mn-3 on HeLa cells without a significant effect in the absence of light.Altogether,these results underline the potential of such water-soluble Mn(III)-porphyrins for the development of multimodal approaches combining MRI and PDT.
基金supported by the Province of Nature Science Foundation of Hunan(2022JJ30798)Jiangsu Department of Education for the School of CHIPS at XJTLU(EFP10120240023 and EFP10120240023)XJTLU Research Development Funding(RDF-21-01-027).
文摘Phototherapy has emerged as a promising modality in cancer treatment,garnering considerable attention for its minimal side effects,exceptional spatial selectivity,and optimal preservation of normal tissue function.This innovative approach primarily encompasses three distinct paradigms:Photodynamic Therapy(PDT),Photothermal Therapy(PTT),and Photoimmunotherapy(PIT).Each of these modalities exerts its antitumor effects through unique mechanisms—specifically,the generation of reactive oxygen species(ROS),heat,and immune responses,respectively.However,significant challenges impede the advancement and clinical application of phototherapy.These include inadequate ROS production rates,subpar photothermal conversion efficiency,difficulties in tumor targeting,and unfavorable physicochemical properties inherent to traditional phototherapeutic agents(PTs).Additionally,the hypoxic microenvironment typical of tumors complicates therapeutic efficacy due to limited agent penetration in deep-seated lesions.To address these limitations,ongoing research is fervently exploring innovative solutions.The unique advantages offered by nano-PTs and nanocarrier systems aim to enhance traditional approaches’effectiveness.Strategies such as generating oxygen in situ within tumors or inhibiting mitochondrial respiration while targeting the HIF-1αpathway may alleviate tumor hypoxia.Moreover,utilizing self-luminescent materials,near-infrared excitation sources,non-photoactivated sensitizers,and wireless light delivery systems can improve light penetration.Furthermore,integrating immunoadjuvants and modulating immunosuppressive cell populations while deploying immune checkpoint inhibitors holds promise for enhancing immunogenic cell death through PIT.This review seeks to elucidate the fundamental principles and biological implications of phototherapy while discussing dominant mechanisms and advanced strategies designed to overcome existing challenges—ultimately illuminating pathways for future research aimed at amplifying this intervention’s therapeutic efficacy.
文摘Nanoparticles(NPs)exhibit unique physicochemical properties that render them valuable for applications in several fields,such as drug delivery and diagnostics.However,these properties can lead to adverse biological reactions,including cell toxicity.The mechanisms of NP-induced cytotoxicity involve complex pathways,including the generation of oxidative stress,reactive oxygen species(ROS),protein corona formation,and interactions with cell-uptake processes such as endocytosis and phagocytosis.This review discusses the in vivo and in vitro assays that help assess NP toxicity,covering cell viability,ROS generation,genotoxicity,and apoptosis.It highlights the importance of selecting appropriate methods to accurately evaluate the risks posed by NPs.The implications of these findings underscore the need for carefully formulating NP design to mitigate cytotoxic effects,ensuring safe and effective medical and industrial applications.
基金supported by the Fund for National Key R&D Program of China(No.2021YFC3200401)the National Natural Science Foundation of China(Nos.52170024,21677015,22006031).
文摘Plastic products widespread in natural water can be broken into smaller-sized microplastics(MPs,<5 mm)under light irradiation,thermal degradation and biodegradation,posing a serious threat to aquatic ecosystems and human health.This perspective concludes that MPs can generate reactive oxygen species(ROS)through initiation,propagation and termination steps,which can attack the polymer resulting in the photoaging and breakdown of C–C and C–H bonds under ultraviolet(UV)irradiation.Free radical generation and weathering degree of MPs depend on their physicochemical properties and environmental conditions.In general,UV irradiation and co-existed MPs can significantly accelerate MP photoaging.With plentiful chromophores carbonyl,carboxyl and benzene rings,Dissolved organic matter(DOM)mainly absorbs photons(300–500 nm)and generates hydrated electrons,^(3)DOM^(*) and ROS,which may affect MP photoaging.However,whether DOM may transfer the electron and energy to MPs under UV irradiation,affect ROS generation of MPs and their photoaging pathway are inadequately studied.More studies are needed to elucidate MP photoaging pathways and mechanisms,consider the influence of stabilization capacity,photosensitization and photoionization of DOM as well as their competitive light absorption with MPs,which provides valuable insights into the environmental behavior and ecological risk of MPs in natural water.
基金supported by the National Natural Science Foundation of China(81790633,61922047,81830054,81902412,81903184,81988101,91859205,21788102,51620105009)the Innovation Program of Shanghai Municipal Education Commission(2019-01-07-0007-E00065,21XD1404600)+4 种基金the Research Grants Council of Hong Kong(16306620,N_HKUST609/19 and C6014-20W)the Innovation and Technology Commission(ITC-CNERC14SC01,ITCPD/17-9,MHP/047/19 and ITS/301/18FX)the support of Shanghai Key Laboratory of Hepato-biliary Tumor BiologyMilitary Key Laboratory on Signal Transductionsupported by the Innovation Program of Shanghai Municipal Education Commission。
文摘Ferroptosis is a form of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation and lethal reactive oxygen species(ROS).To date,misregulated ferroptosis has been implicated in several types of cancers,and ferroptosis inducers can be used to promote ferroptosis in tumor cells and play an anti-tumor role.However,the specificity and efficacy of ferroptosis inducers remain unsatisfactory.Here,a new mitochondria-targeted photosensitizer(PS)with aggregation-induced emission(AIE)characteristic named TCSVP was designed,which efficiently generates ROS in mitochondria after light exposure.TCSVP administration significantly sensitizes tumor cells to ferroptosis inducer(RSL3)-mediated cell death by specifically and light-dependently triggering a moderate ROS generation in vitro and in vivo.Mechanically,the expression levels of ferroptosis related proteins Acyl-CoA synthetase long-chain family member 4(FACL4/ACSL4)and cyclooxygenase-2(COX2)were increased in TCSVP/RSL3-treated cells after light exposure,coupled with decreased Glutathione peroxidase 4(GPX4)activity and excessive malondialdehyde(MDA)accumulation.This study declared that light-induced moderate ROS generation within mitochondria in cancer cells by AIE-PS can be used to enhance the specificity and efficacy of ferroptosis inducers,bringing a new synergistic strategy for tumor intervention.
文摘The present study describes the development and evaluation of a novel biocompatible dendrimer-based nano drug delivery system which is readily soluble in water prepared by condensing Phloroglucinol and Succinic Acid(PGSA)and could efficiently encapsulate a well known hydrophobic photodynamic therapy(PDT)agent,protoporphyrin IX(PpIX).The(dark and photo)cytotoxicity of the PGSA-PpIX(dendrimer-drug)formulation towards Dalton Lymphoma Ascites(DLA)cancer cell lines upon visible light treatment is reported and evaluated the cytotoxic Reactive Oxygen Species(ROS)generation efficiency of the Protoporphyrin IX in free and dendrimer encapsulated forms.The in vitro toxicity demonstrated by PpIX loaded PGSA dendrimer nanoformulation,on DLA cells reveals that this novel PGSA nanocarrier reduces the toxic nature of PpIX when compared to free PpIX without light treatment which satisfy the aim of our study.On the other hand,treatment of DLA cells with PGSA dendrimer formulation in combination with light resulted in significant enhancement in therapeutic efficacy of the PDT agent,PpIX.
基金Grateful acknowledgements are extended to SERB(DST)(ECR/2017/000355),UGC-BSR Start-up grant for providing nesearch funds which was used partly to accomplish this piece of workAuthors thank University of Kalyani(PRG and DST-PURSE)for their minor research funding which was used for the pupose of this work.
文摘Objectives:Pesticide toxicity has become one of the major environmental menaces affecting all types of life forms of the ecosystem.Pesticides get washed off from agricultural fields into nearby water bodies and enter the aquatic organisms.Their bio-accumulated form finally reaches the human race,through consumption of pesticide infested aquatic animals,causing several physiological dysfunctions.Hence it becomes necessary to find a therapeutic cure/a preventive measure to stop the health hazard issues of pesticide.With this projection a search for a phyto-based-product was made whose primary objective would be to lower the pesticidal toxicity in fish and simultaneously in the human race.Methods:In this study we tried to check whether the phyto-chemical,Chlorophyllin(CHL),known for its anti-genotoxic,anti-oxidant activities,could render any kind of protection against Cypermethrin(CM)induced-toxicity in fish model and mammalian cell line L6.Both the model L6 and fish were pre-treated with CHL prior to exposure of CM.Different scientific parameters like%cellular cytotoxicity,reactive oxygen species(ROS)generation,nuclear condensation,etc were checked to validate the possibility of CHL in protecting CM-induced toxicity.Results:The overall results revealed that pre-treatment with CHL could restrict the ROS generation leading to modulation in associated cytokine proteins expression NFkβand IFNγ.Further,CHL lowered nuclear condensation and elevated expression of DNA repair proteins p53 and PARP,showing a kind of pre-activation of signalling cascades for overall protection against the severity of pesticidal toxicity.Conclusion:Thus,this phyto-based preventive approach would possibly solve many areas of human health issues related to pesticide toxicity in future.
基金supported by the National Natural Science Foundation of China(No.51802209),the National Research Programs from Ministry of Science and Technology(MOST)of China(No.2016YFA0201200)the Natural Science Foundation of Jiangsu Province(No.BK20180848)+1 种基金the China Postdoctoral Science Foundation(No.2018T110545)the Collaborative Innovation Center of Suzhou Nano Science and Technology,and the 111 Program from the Ministry of Education of China.
文摘Construction of multifunctional stimuli-responsive nanotherapeutics enabling improved intratumoral penetration of therapeutics and reversal of multiple-drug resistance(MDR)is potent to achieve effective cancer treatment.Herein,we report a general method to synthesize pH-dissociable calcium carbonate(CaCO_(3))hollow nanoparticles with amorphous CaCO_(3)as the template,gallic acid(GA)as the organic ligand,and ferrous ions as the metallic center via a one-pot coordination reaction.The obtained GA–Fe@CaCO_(3)exhibits high loading efficiencies to both oxidized cisplatin prodrug and doxorubicin,yielding drug loaded GA-Fe@CaCO_(3)nanotherapeutics featured in pH-responsive size shrinkage,drug release,and Fenton catalytic activity.Compared to nonresponsive GA-Fe@silica nanoparticles prepared with silica nanoparticles as the template,such GA-Fe@CaCO_(3)confers significantly improved intratumoral penetration capacity.Moreover,both types of drug-loaded GA–Fe@CaCO_(3)nanotherapeutics exhibit synergistic therapeutic efficacies to corresponding MDR cancer cells because of the GA–Fe mediated intracellular oxidative stress amplification that could reduce the efflux of engulfed drugs by impairing the mitochondrial-mediated production of adenosine triphosphate(ATP).As a result,it is found that the doxorubicin loaded GA-Fe@CaCO_(3)exhibits superior therapeutic effect towards doxorubicin-resistant 4T1 breast tumors via combined chemodynamic and chemo-therapies.This work highlights the preparation of pH-dissociable CaCO_(3)-based nanotherapeutics to enable effective tumor penetration for enhanced treatment of drug-resistant tumors.
