Challenges in the prevention and treatment of mild cognitive impairment associated with Alzheimer's disease:Increased life expectancy due to advancements in medical care has given rise to an aging population,accom...Challenges in the prevention and treatment of mild cognitive impairment associated with Alzheimer's disease:Increased life expectancy due to advancements in medical care has given rise to an aging population,accompanied by a surge in the incidence of incurable neurodegenerative diseases(NDDs).These diseases primarily affect the cognitive and behavioral functions of older adults by impacting brain activity.Mild cognitive impairment(MCI)is a neurodegenerative condition that affects a significant portion of the population.展开更多
Objective: To investigate the composition of volatile compounds in the different accessions of Perilla frutescens(P. frutescens) collected from various habitats of China and Japan. Methods: In the present study, the e...Objective: To investigate the composition of volatile compounds in the different accessions of Perilla frutescens(P. frutescens) collected from various habitats of China and Japan. Methods: In the present study, the essential oil from the leaves of P. frutescens cultivars from China and Japan was extracted by hydro-distillation and the chemical composition and concentration of the volatile components present in the oils were determined by gas chromatography–mass spectrometry(GC–MS) analysis. Results: Among the volatile components, the major proportion was of perilla ketone, which was followed by elemicin and beta-caryophyllene in the Chinese Perilla cultivars. The main component in the oil extracted from the Japanese accessions was myristicin, which was followed by perilla ketone and beta-caryophyllene. We could distinguish seven chemotypes, namely the perilla ketone(PK) type, perilla ketone, myristicin(PM) type, perilla ketone, unknown(PU) type, perilla ketone, beta-caryophyllene, myristicine(PB) type, perilla ketone, myristicin, unknown(PMU) type, perilla ketone, elemicine, myristicin, beta-caryophyllene(PEMB) type, and the perilla ketone, limonene, betacryophyllene, myristicin(L) type. Most of the accessions possessed higher essential oil content before the flowering time than at the flowering stage. The average plant height, leaf length, leaf width of the Chinese accessions was higher than those of the Japanese accessions. Conclusion:The results revealed that the harvest time and geographical origin caused polymorphisms in the essential oil composition and morphological traits in the Perilla accessions originating from China and Japan. Therefore, these chemotypes with desirable characters might be useful for industrial exploitation and for determining the harvest time.展开更多
Objective:To investigate the antifibrotic effects of Chrysanthemum indicum ethanol extract(CIEE)against activated hepatic stellate cells(HSC)and thioacetamide(TAA)-induced hepatofibrosis in rats.Methods:Cell viability...Objective:To investigate the antifibrotic effects of Chrysanthemum indicum ethanol extract(CIEE)against activated hepatic stellate cells(HSC)and thioacetamide(TAA)-induced hepatofibrosis in rats.Methods:Cell viability and proliferation of HSC-T6 cells were measured using MTT assay.Primary HSCs were used to study morphology.TAA(200 mg/kg)was used to induced hepatic fibrosis in rats.CIEE(100 and 500 mg/kg)and silymarin(50 mg/kg)were administered orally.Liver functions including alanine transaminase,aspartate transaminase,glutathione,and hydroxyproline levels were measured using commercial kits.Liver sections and fibrotic biomarker expression were measured using hematoxylin and eosin staining and real-time polymerase chain reaction.Results:In vitro study revealed that CIEE(0.1,0.25,and 0.5 mg/mL)inhibited the proliferation of activated HSCs exposed to transforming growth factor(TGF)-β and restored the activated primary HSC morphology.In in vivo studies,TAA-induced increase in liver/body weight ratio(5.46±0.26)was significantly reduced(4.13±0.22)by CIEE(P<0.05 at 500 mg/kg).CIEE(100 and 500 mg/kg)improved the liver functions by significantly attenuating changes in alanine transaminase,aspartate transaminase,glutathione,and hydroxyproline levels(P<0.05).Further,CIEE(100 and 500 mg/kg)ameliorated the histological changes in liver tissue and TGF-β expression significantly(P<0.05)in TAA-induced rats.Conclusions:CIEE significantly protects against TAA-induced liver damage in rats and can be used in the treatment of liver fibrosis.展开更多
Background: Radiofrequency has been proven to penetrate deeper than optical light sources independent of skin color allowing a safer treatment for the Asian skin type. Many studies have indicated the efficacy of vario...Background: Radiofrequency has been proven to penetrate deeper than optical light sources independent of skin color allowing a safer treatment for the Asian skin type. Many studies have indicated the efficacy of various types of devices, but have not included a sufficient objective evaluation. Multisource radiofrequency uses multiple phase controlled radiofrequency generators with real time impedance control, allowing painless, deeper dermal heating with better adaptation to differences in individual skin impedance. In this study we used three-dimensional imaging for the objective evaluation of facial skin tightening by multisource phase-controlled radiofrequency. Methods: Twenty Japanese patients were treated with a multisource phase-controlled radiofrequency device. Three-dimensional imaging was performed with a Canfield Scientific Vectra camera and software, and quantitative volume measurements were taken to evaluate the change in the post-treatment volume. The patients then provided subjective assessments. Results: Objective assessments of the treated cheek volume evaluated by a three-dimensional color schematic representation with quantitative volume measurements showed significant improvement three months after the final treatment. The mean volume reduction at the last post-treatment visit was 3.878 ± 2.86 mL. The post-treatment volume was significantly reduced compared to the pretreatment volume in all of the volunteers (P = 0.0007). Ninety-five percent of volunteers reported satisfaction with the improvement of skin laxity, and ninety percent of volunteers reported satisfaction with the improvement of wrinkles, such as the nasolabial folds. Conclusions: The advantages of these multisource phase-controlled radiofrequency treatments are its high efficacy for skin tightening associated with minimal level of discomfort, minimal side effects, and low cost. Taken together, these characteristics facilitate the ability to give repeated treatments as a stand alone treatment or adjunct to surgery. This study provides for the first time a qualitative and quantitative volumetric assessment, proving the ability of the technology to reduce the volume through non invasive skin tightening.展开更多
Several Asian natricine snakes of the genus Rhabdophis feed on toads and sequester steroidal cardiac toxins known as bufadienolides(BDs)from them.A recent study revealed that species of the Rhabdophis nuchalis Group i...Several Asian natricine snakes of the genus Rhabdophis feed on toads and sequester steroidal cardiac toxins known as bufadienolides(BDs)from them.A recent study revealed that species of the Rhabdophis nuchalis Group ingest lampyrine fireflies to sequester BDs.Although several species of fireflies are distributed in the habitat of the R.nuchalis Group,only lampyrine fireflies,which have BDs,are included in the diet of these snakes.Thus,we hypothesized that the R.nuchalis Group chemically distinguishes fireflies that have BDs from those that do not have BDs.We also predicted that the R.nuchalis Group detects BDs as the chemical cue of toxin source.To test these predictions,we conducted 3 behavioral experiments using Rhabdophis chiwen,which belongs to the R.nuchalis Group.In the first experiment,R.chiwen showed a moderate tongue flicking response to cinobufagin,a compound of BDs.On the other hand,the snake showed a higher response to the chemical stimuli of lampyrine fireflies(BD fireflies)than those of lucioline fireflies(non-BD fireflies).In the second experiment,in which we provided live BD and non-BD fireflies,the snake voluntarily consumed only the former.In the third,a Y-maze experiment,the snake tended to select the chemical trail of BD fireflies more frequently than that of non-BD fireflies.These results demonstrated that R.chiwen discriminates BD fireflies from non-BD fireflies,but the prediction that BDs are involved in this discrimination was not fully supported.To identify the proximate mechanisms of the recognition of novel toxic prey in the R.nuchalis Group,further investigation is necessary.展开更多
Sunlight that reaches the human skin contains solar energy composed of 6.8%ultraviolet(UV),38.9%visible light and 54.3%infrared radiation.In addition to natural near-infrared(NIR),human skin is increasingly exposed to...Sunlight that reaches the human skin contains solar energy composed of 6.8%ultraviolet(UV),38.9%visible light and 54.3%infrared radiation.In addition to natural near-infrared(NIR),human skin is increasingly exposed to artificial NIR from medical devices and electrical appliances.Thus,we are exposed to tremendous amounts of NIR.Many studies have proven the effects of UV exposure on human skin and skin cancers but have not investigated well the effects of NIR exposure.Furthermore,many of the previous NIR studies have used NIR resources without a water filter or a contact cooling.With these resources,a substantial amount of NIR energy is absorbed in the superficial layers and only limited NIR energy can be delivered to deeper tissues.Thus,they could not sufficiently evaluate the effects of incident solar NIR.In order to simulate solar NIR that reaches the skin,a water filter is essential because solar NIR is filtered by atmospheric water.In reality,NIR increases the surface temperature and induces thermal effects so a contact cooling is needed to pursue the properties of NIR.I clarify that NIR can penetrate the skin and non-thermally affect the subcutaneous tissues,including muscle and bone marrow,using a NIR resource with a water filter and a coolingsystem.I would like to emphasize the biological effects of NIR which have both merits and demerits.Appropriate NIR irradiation induces dermal heating thermally and non-thermally induces collagen and elastin stimulation,which results in skin tightening.NIR also induces non-thermal DNA damage of mitotic cells,which may have the potential application for treating cancer.However,as continuous NIR exposure may induce photoaging and potentially photocarcinogenesis,we should consider the effect of,not only UV,but also NIR and the necessity for protection against solar NIR.Here,this paper introduces the new aspects of the biological effects of NIR radiation.展开更多
In light of the burgeoning successes of cancer immunotherapy,glioblastoma(GBM)remains refractory due to an immunosuppressive microenvironment originating from its molecular heterogeneity.Thus,identifying promising the...In light of the burgeoning successes of cancer immunotherapy,glioblastoma(GBM)remains refractory due to an immunosuppressive microenvironment originating from its molecular heterogeneity.Thus,identifying promising therapeutic targets for treating GBM and discovering methodologies to effectively regulate them is still a tremendous challenge.Here we describe photodynamic protein tyrosine phosphatase 1B(PTP1B)proteolysis mediated by a proteolysis-targeting chimera(PROTAC)nanoassembly.The PTP1B-targeting PROTAC is conjugated with a photosensitizer via a cathepsin B(Cat B)-cleavable peptide,which spontaneously forms nanoassemblies due to intermolecularπ-πstack-ing interactions.In GBM models,PROTAC nanoassemblies significantly accumulate in the tumor region across the disrupted blood-brain barrier(BBB),triggering a burst release of the photosensitizer and active PROTAC by Cat B-mediated enzymatic cleavage.Upon laser irradiation,photodynamic therapy(PDT)synergizes with PROTAC-mediated PTP1B proteolysis to induce potent immunogenic cell death(ICD)in tumor cells.Subsequently,persistent PTP1B degradation by nanoassemblies in Cat B-overexpressed intratumoral T cells downregulates exhaustion markers,reinvigorating their function-ality.These sequential processes of photodynamic PTP1B proteolysis ultimately augment T cellmediated antitumor immunity as well as protective immunity,completely eradicating the primary GBM and preventing its recurrence.Overall,our findings underscore the therapeutic potential of combining PDT with PROTAC activity for GBM immunotherapy.展开更多
Two new compounds cadin-2-en-1β-ol-1β-D-glucuronopyranoside （1）, guaia-l,7-dien-3β,13-diol-13α-D- glucofuranoside （2） along with three known compounds have been isolated from the culture hairy roots of Cathara...Two new compounds cadin-2-en-1β-ol-1β-D-glucuronopyranoside （1）, guaia-l,7-dien-3β,13-diol-13α-D- glucofuranoside （2） along with three known compounds have been isolated from the culture hairy roots of Catharanthus roseus. Their structures have been elucidated with the help of 500 MHz NMR using 1D and 2D spectral methods： viz： ^1H and ^13C NMR, ^1H-^1H COSY, ^1H-^13C HETCOR and DEPT aided by ELMS, FAB-MS, HR-FABMS and IR spectroscopy.展开更多
Photodynamic therapy(PDT)induces tumor cell pyroptosis,a form of programmed cell death that triggers antitumor immunity.However,high glucose metabolism and hypoxic conditions in the tumor microenvironment(TME)limit PD...Photodynamic therapy(PDT)induces tumor cell pyroptosis,a form of programmed cell death that triggers antitumor immunity.However,high glucose metabolism and hypoxic conditions in the tumor microenvironment(TME)limit PDT efficiency and impair effector cell function.Here,we propose a cancer metabolic reprogramming-enabling photoresponsive nanoproteolysis-targeting chimera(Nano-PROTAC;NanoTAC),derived from the supramolecular self-assembly of drug conjugates that bridge a PROTAC targeting hexokinaseⅡ(HK2)and a photosensitizer via a biomarker-cleavable linker.In a triple-negative breast cancer(TNBC)model,NanoTAC initially silences PROTAC activity and accumulates in tumor regions,where it undergoes linker cleavage in response to enzymatic biomarkers.Upon photoirradiation,PDT-induced pyroptotic cell death promotes the release of tumor-associated antigens(TAAs)and damage-associated molecular patterns(DAMPs)to drive the cancer-immunity cycle.Concurrently,targeted protein degradation(TPD)via PROTACs counteracts glucose and oxygen consumption in the TME,ultimately potentiating pyroptosis-mediated photoimmunotherapy.This combination therapy achieves a high rate of complete regression in primary TNBC and confers adaptive immunity to prevent metastasis and recurrence.Our study presents a rationally designed nanomedicine that integrates PDT and PROTACs,shedding light on strategies for more effective cancer immunotherapy.展开更多
基金supported by The Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(RS-2023-00244901)(to RB)。
文摘Challenges in the prevention and treatment of mild cognitive impairment associated with Alzheimer's disease:Increased life expectancy due to advancements in medical care has given rise to an aging population,accompanied by a surge in the incidence of incurable neurodegenerative diseases(NDDs).These diseases primarily affect the cognitive and behavioral functions of older adults by impacting brain activity.Mild cognitive impairment(MCI)is a neurodegenerative condition that affects a significant portion of the population.
基金supported by funding from the Konkuk University Brain Pool
文摘Objective: To investigate the composition of volatile compounds in the different accessions of Perilla frutescens(P. frutescens) collected from various habitats of China and Japan. Methods: In the present study, the essential oil from the leaves of P. frutescens cultivars from China and Japan was extracted by hydro-distillation and the chemical composition and concentration of the volatile components present in the oils were determined by gas chromatography–mass spectrometry(GC–MS) analysis. Results: Among the volatile components, the major proportion was of perilla ketone, which was followed by elemicin and beta-caryophyllene in the Chinese Perilla cultivars. The main component in the oil extracted from the Japanese accessions was myristicin, which was followed by perilla ketone and beta-caryophyllene. We could distinguish seven chemotypes, namely the perilla ketone(PK) type, perilla ketone, myristicin(PM) type, perilla ketone, unknown(PU) type, perilla ketone, beta-caryophyllene, myristicine(PB) type, perilla ketone, myristicin, unknown(PMU) type, perilla ketone, elemicine, myristicin, beta-caryophyllene(PEMB) type, and the perilla ketone, limonene, betacryophyllene, myristicin(L) type. Most of the accessions possessed higher essential oil content before the flowering time than at the flowering stage. The average plant height, leaf length, leaf width of the Chinese accessions was higher than those of the Japanese accessions. Conclusion:The results revealed that the harvest time and geographical origin caused polymorphisms in the essential oil composition and morphological traits in the Perilla accessions originating from China and Japan. Therefore, these chemotypes with desirable characters might be useful for industrial exploitation and for determining the harvest time.
文摘Objective:To investigate the antifibrotic effects of Chrysanthemum indicum ethanol extract(CIEE)against activated hepatic stellate cells(HSC)and thioacetamide(TAA)-induced hepatofibrosis in rats.Methods:Cell viability and proliferation of HSC-T6 cells were measured using MTT assay.Primary HSCs were used to study morphology.TAA(200 mg/kg)was used to induced hepatic fibrosis in rats.CIEE(100 and 500 mg/kg)and silymarin(50 mg/kg)were administered orally.Liver functions including alanine transaminase,aspartate transaminase,glutathione,and hydroxyproline levels were measured using commercial kits.Liver sections and fibrotic biomarker expression were measured using hematoxylin and eosin staining and real-time polymerase chain reaction.Results:In vitro study revealed that CIEE(0.1,0.25,and 0.5 mg/mL)inhibited the proliferation of activated HSCs exposed to transforming growth factor(TGF)-β and restored the activated primary HSC morphology.In in vivo studies,TAA-induced increase in liver/body weight ratio(5.46±0.26)was significantly reduced(4.13±0.22)by CIEE(P<0.05 at 500 mg/kg).CIEE(100 and 500 mg/kg)improved the liver functions by significantly attenuating changes in alanine transaminase,aspartate transaminase,glutathione,and hydroxyproline levels(P<0.05).Further,CIEE(100 and 500 mg/kg)ameliorated the histological changes in liver tissue and TGF-β expression significantly(P<0.05)in TAA-induced rats.Conclusions:CIEE significantly protects against TAA-induced liver damage in rats and can be used in the treatment of liver fibrosis.
文摘Background: Radiofrequency has been proven to penetrate deeper than optical light sources independent of skin color allowing a safer treatment for the Asian skin type. Many studies have indicated the efficacy of various types of devices, but have not included a sufficient objective evaluation. Multisource radiofrequency uses multiple phase controlled radiofrequency generators with real time impedance control, allowing painless, deeper dermal heating with better adaptation to differences in individual skin impedance. In this study we used three-dimensional imaging for the objective evaluation of facial skin tightening by multisource phase-controlled radiofrequency. Methods: Twenty Japanese patients were treated with a multisource phase-controlled radiofrequency device. Three-dimensional imaging was performed with a Canfield Scientific Vectra camera and software, and quantitative volume measurements were taken to evaluate the change in the post-treatment volume. The patients then provided subjective assessments. Results: Objective assessments of the treated cheek volume evaluated by a three-dimensional color schematic representation with quantitative volume measurements showed significant improvement three months after the final treatment. The mean volume reduction at the last post-treatment visit was 3.878 ± 2.86 mL. The post-treatment volume was significantly reduced compared to the pretreatment volume in all of the volunteers (P = 0.0007). Ninety-five percent of volunteers reported satisfaction with the improvement of skin laxity, and ninety percent of volunteers reported satisfaction with the improvement of wrinkles, such as the nasolabial folds. Conclusions: The advantages of these multisource phase-controlled radiofrequency treatments are its high efficacy for skin tightening associated with minimal level of discomfort, minimal side effects, and low cost. Taken together, these characteristics facilitate the ability to give repeated treatments as a stand alone treatment or adjunct to surgery. This study provides for the first time a qualitative and quantitative volumetric assessment, proving the ability of the technology to reduce the volume through non invasive skin tightening.
基金This study was supported in part by Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research(17H03719,18KK0205,and 21H02551).
文摘Several Asian natricine snakes of the genus Rhabdophis feed on toads and sequester steroidal cardiac toxins known as bufadienolides(BDs)from them.A recent study revealed that species of the Rhabdophis nuchalis Group ingest lampyrine fireflies to sequester BDs.Although several species of fireflies are distributed in the habitat of the R.nuchalis Group,only lampyrine fireflies,which have BDs,are included in the diet of these snakes.Thus,we hypothesized that the R.nuchalis Group chemically distinguishes fireflies that have BDs from those that do not have BDs.We also predicted that the R.nuchalis Group detects BDs as the chemical cue of toxin source.To test these predictions,we conducted 3 behavioral experiments using Rhabdophis chiwen,which belongs to the R.nuchalis Group.In the first experiment,R.chiwen showed a moderate tongue flicking response to cinobufagin,a compound of BDs.On the other hand,the snake showed a higher response to the chemical stimuli of lampyrine fireflies(BD fireflies)than those of lucioline fireflies(non-BD fireflies).In the second experiment,in which we provided live BD and non-BD fireflies,the snake voluntarily consumed only the former.In the third,a Y-maze experiment,the snake tended to select the chemical trail of BD fireflies more frequently than that of non-BD fireflies.These results demonstrated that R.chiwen discriminates BD fireflies from non-BD fireflies,but the prediction that BDs are involved in this discrimination was not fully supported.To identify the proximate mechanisms of the recognition of novel toxic prey in the R.nuchalis Group,further investigation is necessary.
文摘Sunlight that reaches the human skin contains solar energy composed of 6.8%ultraviolet(UV),38.9%visible light and 54.3%infrared radiation.In addition to natural near-infrared(NIR),human skin is increasingly exposed to artificial NIR from medical devices and electrical appliances.Thus,we are exposed to tremendous amounts of NIR.Many studies have proven the effects of UV exposure on human skin and skin cancers but have not investigated well the effects of NIR exposure.Furthermore,many of the previous NIR studies have used NIR resources without a water filter or a contact cooling.With these resources,a substantial amount of NIR energy is absorbed in the superficial layers and only limited NIR energy can be delivered to deeper tissues.Thus,they could not sufficiently evaluate the effects of incident solar NIR.In order to simulate solar NIR that reaches the skin,a water filter is essential because solar NIR is filtered by atmospheric water.In reality,NIR increases the surface temperature and induces thermal effects so a contact cooling is needed to pursue the properties of NIR.I clarify that NIR can penetrate the skin and non-thermally affect the subcutaneous tissues,including muscle and bone marrow,using a NIR resource with a water filter and a coolingsystem.I would like to emphasize the biological effects of NIR which have both merits and demerits.Appropriate NIR irradiation induces dermal heating thermally and non-thermally induces collagen and elastin stimulation,which results in skin tightening.NIR also induces non-thermal DNA damage of mitotic cells,which may have the potential application for treating cancer.However,as continuous NIR exposure may induce photoaging and potentially photocarcinogenesis,we should consider the effect of,not only UV,but also NIR and the necessity for protection against solar NIR.Here,this paper introduces the new aspects of the biological effects of NIR radiation.
基金supported by grants from the National Research Foundation(NRF)of Korea,funded by the Ministry of Science(RS-2025-02219039,RS-2021-NR061836,RS-202400343156,NRF-2022R1A2C2006861,RS-2024-00463774,RS2022-NR068161 and RS-2024-00405287)the Intramural Research Program of KIST.
文摘In light of the burgeoning successes of cancer immunotherapy,glioblastoma(GBM)remains refractory due to an immunosuppressive microenvironment originating from its molecular heterogeneity.Thus,identifying promising therapeutic targets for treating GBM and discovering methodologies to effectively regulate them is still a tremendous challenge.Here we describe photodynamic protein tyrosine phosphatase 1B(PTP1B)proteolysis mediated by a proteolysis-targeting chimera(PROTAC)nanoassembly.The PTP1B-targeting PROTAC is conjugated with a photosensitizer via a cathepsin B(Cat B)-cleavable peptide,which spontaneously forms nanoassemblies due to intermolecularπ-πstack-ing interactions.In GBM models,PROTAC nanoassemblies significantly accumulate in the tumor region across the disrupted blood-brain barrier(BBB),triggering a burst release of the photosensitizer and active PROTAC by Cat B-mediated enzymatic cleavage.Upon laser irradiation,photodynamic therapy(PDT)synergizes with PROTAC-mediated PTP1B proteolysis to induce potent immunogenic cell death(ICD)in tumor cells.Subsequently,persistent PTP1B degradation by nanoassemblies in Cat B-overexpressed intratumoral T cells downregulates exhaustion markers,reinvigorating their function-ality.These sequential processes of photodynamic PTP1B proteolysis ultimately augment T cellmediated antitumor immunity as well as protective immunity,completely eradicating the primary GBM and preventing its recurrence.Overall,our findings underscore the therapeutic potential of combining PDT with PROTAC activity for GBM immunotherapy.
文摘Two new compounds cadin-2-en-1β-ol-1β-D-glucuronopyranoside （1）, guaia-l,7-dien-3β,13-diol-13α-D- glucofuranoside （2） along with three known compounds have been isolated from the culture hairy roots of Catharanthus roseus. Their structures have been elucidated with the help of 500 MHz NMR using 1D and 2D spectral methods： viz： ^1H and ^13C NMR, ^1H-^1H COSY, ^1H-^13C HETCOR and DEPT aided by ELMS, FAB-MS, HR-FABMS and IR spectroscopy.
基金supported by grants from the National Research Foundation(NRF)of Korea,funded by the Ministry of Science(RS-2025-02219039,RS-2025-02217286,RS-2024-00351420,RS-2024-00405287,RS-2024-00463774,and RS-2021-NR061836)the Intramural Research Program of KIST.
文摘Photodynamic therapy(PDT)induces tumor cell pyroptosis,a form of programmed cell death that triggers antitumor immunity.However,high glucose metabolism and hypoxic conditions in the tumor microenvironment(TME)limit PDT efficiency and impair effector cell function.Here,we propose a cancer metabolic reprogramming-enabling photoresponsive nanoproteolysis-targeting chimera(Nano-PROTAC;NanoTAC),derived from the supramolecular self-assembly of drug conjugates that bridge a PROTAC targeting hexokinaseⅡ(HK2)and a photosensitizer via a biomarker-cleavable linker.In a triple-negative breast cancer(TNBC)model,NanoTAC initially silences PROTAC activity and accumulates in tumor regions,where it undergoes linker cleavage in response to enzymatic biomarkers.Upon photoirradiation,PDT-induced pyroptotic cell death promotes the release of tumor-associated antigens(TAAs)and damage-associated molecular patterns(DAMPs)to drive the cancer-immunity cycle.Concurrently,targeted protein degradation(TPD)via PROTACs counteracts glucose and oxygen consumption in the TME,ultimately potentiating pyroptosis-mediated photoimmunotherapy.This combination therapy achieves a high rate of complete regression in primary TNBC and confers adaptive immunity to prevent metastasis and recurrence.Our study presents a rationally designed nanomedicine that integrates PDT and PROTACs,shedding light on strategies for more effective cancer immunotherapy.
