Colorectal cancer(CRC)is one of the most prevalent malignant tumors worldwide,exhibiting high morbidity and mortality.Lack of efficient tools for early diagnosis and surgical resection guidance of CRC have been a seri...Colorectal cancer(CRC)is one of the most prevalent malignant tumors worldwide,exhibiting high morbidity and mortality.Lack of efficient tools for early diagnosis and surgical resection guidance of CRC have been a serious threat to the long-term survival rate of the CRC patients.Recent studies have shown that relative higher viscosity was presented in tumor cells compared to that in normal cells,leading to viscosity as a potential biomarker for CRC.Herein,we reported the development of a series of novel viscosity-sensitive and mitochondria-specific fluorescent probes(HTB,HTI,and HTP)for CRC detection.Among them,HTB showed high sensitivity,minimal background interference,low cytotoxicity,and significant viscous response capability,making it an ideal tool for distinguishing colorectal tumor cells from normal cells.Importantly,we have successfully utilized HTB to visualize in a CRC-cells-derived xenograft(CDX)model,enriching its medical imaging capacity,which laid a foundation for further clinical translational application.展开更多
Objectives:Triphenylphosphine(TPP)and Doxorubicin(DOX)were conjugated to obtain Triphenylphosphine-Doxorubicin(TPP-DOX),which was applied in tumor cells for enhancement of DOX in mitochondria targeting.The study focus...Objectives:Triphenylphosphine(TPP)and Doxorubicin(DOX)were conjugated to obtain Triphenylphosphine-Doxorubicin(TPP-DOX),which was applied in tumor cells for enhancement of DOX in mitochondria targeting.The study focused on investigating the anti-tumor effect of TPP-DOX in combination with radiotherapy throughout in vitro and in vivo studies.Methods:TPP-DOX was synthesized using the carbodiimide method.In vitro experiments were conducted with 4T1 cells(mouse breast cancer cell line)to assess apoptosis induction,mitochondrial targeting,reactive oxygen species(ROS)production,and mitochondrial membrane potential.The research evaluates the effects of TPP-DOX,DOX,and their combinations with radiotherapy.A nude mouse tumor heterograft model was established to investigate the synergistic effect of TPP-DOX and radiotherapy.Results:TPP-DOX was successfully synthesized and scrupulously verified.In vitro experiments showed that compared to DOX,TPP-DOX exhibited enhanced tumor cytotoxicity,improved cellular uptake in 4T1 cells,and increased apoptosis induction.Combined with radiotherapy,TPP-DOX promoted mitochondrial ROS production,reduced mitochondrial membrane potential,and amplified its anti-tumor effect.In vivo experiment confirmed that TPP-DOX combined with radiotherapy exhibited superior anti-tumor activity,promoted tumor tissue apoptosis,inhibited tumor angiogenesis,and showed a favorable in vivo safety profile.Conclusion:The study confirmed that when combined with radiotherapy,TPP-DOX promoted tumor cell apoptosis,and effectively enhanced the anti-tumor effect.In sensitive cells,TPP-DOX demonstrates comparable efficacy to DOX when combined with radiotherapy.TPP-DOX holds significant potential for a broader spectrum of applications and emerges as a valuable candidate for clinical application.These findings provide a promising and efficient therapeutic strategy for tumor treatment with improved efficacy and safety.展开更多
Mitochondria are well-acknowledged as ideal targets for tumor therapy due to their important role in energy supply and cellular signal regulation.Mitochondria-specific photosensitizers have been reported to be critica...Mitochondria are well-acknowledged as ideal targets for tumor therapy due to their important role in energy supply and cellular signal regulation.Mitochondria-specific photosensitizers have been reported to be critical for inducing cell apoptosis.Two-photon fluorescence imaging provides a new technique for delineating biological structures and activities in deep tissues.Herein,we developed a new aggregation-induced emission(AIE)active photosensitizer by attaching a pyridinium group for mitochondrial target-ing.The rationally designed photosensitizer(TTTP)exhibited excellent photophysical properties,good biocompatibility,reactive oxygen species(ROS)stimulation ability,anticancer efficacy,and two-photon imaging properties.TTTP was highly taken up by cells and accumulated specifically in mitochondria but was selectively cytotoxic to cancer cells.Under light irradiation,the generation of ROS was significantly boosted,leading to actively induced apoptosis.The in vivo tumor photodynamic therapeutic efficacy of TTTP showed significant inhibition of tumor growth.Furthermore,the underlying mechanism of TTTP tu-mor suppression revealed that the apoptosis agonist Bax was markedly up-regulated while the antagonist Bcl-xL was down-regulated.This research provides a potential mitochondrial-targeted phototherapeutic agent for effective therapy and two-photon fluorescence imaging.展开更多
Homocysteine(Hcy), cysteine(Cys) and glutathione(GSH) play crucial roles in redox homeostasis during mitochondria functions. Simultaneous differentiation and visualization of mitochondrial biothiols dynamics are signi...Homocysteine(Hcy), cysteine(Cys) and glutathione(GSH) play crucial roles in redox homeostasis during mitochondria functions. Simultaneous differentiation and visualization of mitochondrial biothiols dynamics are significant for understanding cell metabolism and their related diseases. Herein, a multisitebinding fluorescent probe(MCP) was developed for simultaneous sensing of mitochondrial Cys, GSH and Hcy from three fluorescence channels for the first time. This novel probe exhibited rapid fluorescence turn-on, good water-solubility, high selectivity and large spectral separation for discriminating Cys, GSH and Hcy with 131-, 96-, 748-fold fluorescence increasement at 471, 520, 567 nm through different excitation wavelengths, respectively. Importantly, this probe was successfully applied to simultaneous monitoring of mitochondrial Cys, GSH, and Hcy in live cells and zebrafish from three fluorescence channels,promoting the understanding of the functions of Hcy, Cys and GSH.展开更多
Mitochondria is the main organelle for the production of reactive sulfur species(RSS), such as homocysteine(Hcy), cysteine(Cys), glutathione(GSH) and sulfur dioxide(SO_(2)). These compounds participate in a large numb...Mitochondria is the main organelle for the production of reactive sulfur species(RSS), such as homocysteine(Hcy), cysteine(Cys), glutathione(GSH) and sulfur dioxide(SO_(2)). These compounds participate in a large number of physiological processes and play an extremely important role in maintaining the balance of life systems. Abnormal concentration and metabolism are closely related to many diseases. Due to their similarities in chemical properties, it is challenging to develop a single fluorescent probe to distinguish them simultaneously. Here, we synthesized the probe PI-CO–NBD with three fluorophores, NBD-Cl and benzopyranate as the reaction sites of GSH/Cys/Hcy and SO_(2), respectively. Three biothiols all could cleavage ether bond to release benzopyrylium and coumarin moiety, which emitted red and blue fluorescence,but Cys/Hcy also could do intramolecular rearrangement after nucleophilic substitution, resulting in yellow fluorescence. Thus the probe can distinguish Cys/Hcy and GSH. Subsequently, only SO_(2)could quench red fluorescence by adding C=C of benzopyrylium. The probe also could localize well in mitochondria by oxonium ion for all kinds of cells. The probe not only could detect above sulfur-containing active substances of intracellular and extracellular but also monitor the level of them under oxidative stress and apoptosis process in living cells and zebrafish.展开更多
Multiple signaling molecules work together in mitochondria to mediate complex physiological processes.However,most current fluorescent probes lack of ability to clarify the function of these actives in mitochondria du...Multiple signaling molecules work together in mitochondria to mediate complex physiological processes.However,most current fluorescent probes lack of ability to clarify the function of these actives in mitochondria due to their non-specific binding with analytes outside mitochondria.In this study,we designed an on-demand light-activated mitochondria-targeted fluorescent probe to observe in situ fluctuations in mitochondrial esterase.The designed probe has a natural yellow fluorescence that monitors entry into the mitochondria and maintains nonfluorescent responsiveness to esterase during cellular delivery.Following the enrichment of the probe in mitochondria,on-demand photoactivation only at the required mitochondrial location resulted in a remarkable emission response to the esterase with red fluorescence at 700 nm.Precise spatiotemporal recognition of esterase in mitochondria is successfully achieved by activating the in situ fluorescence response of esterase by light irradiation.This work provides a new strategy for the study of esterase-related diseases.展开更多
Excessive reactive oxygen species(ROS)-induced mitochondrial damage has impact on osteoarthritis(OA).Nanozyme mimics as natural enzyme alternatives to scavenge excessive ROS has offered a promising strategy for OA the...Excessive reactive oxygen species(ROS)-induced mitochondrial damage has impact on osteoarthritis(OA).Nanozyme mimics as natural enzyme alternatives to scavenge excessive ROS has offered a promising strategy for OA therapy.Herein,we reported a novel mitochondrial-targeting Mn_(3)O_(4)/UIO-TPP nanozyme using metal-organic frameworks with loaded Mn_(3)O_(4)as the enzyme-like active core combining mitochondria-targeting triphenylphosphine(TPP)groups to serve as ROS scavengers for therapy of OA.With sequential catalysis of superoxide dismutase-like,catalase(CAT)-like,and hydroxyl radical(·OH)scavenging potentials,the nanozyme can target mitochondria by crossing subcellular barriers to effectively eliminate ROS to restore mitochondrial function and inhibit inflammation and chondrocyte apoptosis.It also has favorable biocompatibility and biosafety.Based on anterior cruciate ligament transection-induced OA joint models,this mitochondrial-targeting nanozyme effectively mitigated the inflammatory response with the Pelletier score reduction of 49.9%after 8-week therapy.This study offers a prospective approach to the design of nanomedicines for ROS-related diseases.展开更多
Developme nt of subcellular orga nelle-targeted bioimagi ng probes is of great imports nee in the field of early detection of diseases and exploring the behaviors of subcellular organelles.Herein,we present a tripheny...Developme nt of subcellular orga nelle-targeted bioimagi ng probes is of great imports nee in the field of early detection of diseases and exploring the behaviors of subcellular organelles.Herein,we present a triphenyIphosphonium functionalized conjugated macrocyclic tetramaleimide(TPP-CMT)as a mitochondrial-targeting bioimaging probe.The core of TPP-CMT is obtained by connecting two pyrenes and two benzenes through four maleimides.This unique structure endows TPP-CMT with exceptional far red/near-i nfirared aggregati on-induced emissi on(FR/NIR-AIE)characteristics.TPP-CMT is an excelle nt fluoresce nt emitter in most solve nts and eve n in solid states.The qua ntum yield of TPP-CMT was higher tha n 27% when dissolved in comm on middle-polarity orga nic solve nt and this value remained at 28.2% in its solid state.The in troducti on of four triphe ny Iphosph onium on maleimide positions endows TPP-CMT with mitochondrial-targeting ability.Thanks to the FR/NIR-AIE characteristics and the mitochondri-al-targeti ng ability,this well-desig ned fluoresce nt probe was successfully employed for mitochondrial targeti ng bioimaging of HeLa and HepG2 cells.展开更多
Nicotinamide adenine dinucleotide (NAD+/NADH) pools homeostasis is recognized as an Achilles’ Heel in tumor metabolism reprogramming. However, mitochondria can enable cancer cells to overcome NADH exhaustion by provi...Nicotinamide adenine dinucleotide (NAD+/NADH) pools homeostasis is recognized as an Achilles’ Heel in tumor metabolism reprogramming. However, mitochondria can enable cancer cells to overcome NADH exhaustion by providing NAD+ precursors and/or intermediates, thus promoting their survival rate and potentially driving uncontrollable proliferation. Here, a synergistic intervention NAD+/NADH homeostasis and mitochondrial metabolism strategy with magnetic resonance imaging (MRI)/photoacoustic imaging (PAI) are developed to address grand challenge of metabolic reprogramming for antitumor bioenergetic therapy. A mitochondrial-targeted cascade amplification nanoplatform ([β-MQ]TRL), triggered by NAD(P)H: quinone oxidoreductase-1 (NQO1), can enable a continuous depletion of cytosol NADH until cell death. The end-product, hydrogen peroxide (H_(2)O_(2)), can be further catalytically converted to higher toxic ·OH in proximity to mitochondria based on [β-MQ]TRL mediated Fenton-like reaction, hijacking tumorigenic energy sources and leading to mitochondrial dysfunction. Additionally, the mild thermal ablation enabled by [β-MQ]TRL further amplifies this cascade reaction to effectively prevent tumor metastasis and recurrence. This synchronous intervention strategy with MRI/PAI establishes unprecedented efficiency in antitumor bioenergetic therapy in vivo, which shows excellent promise for clinical application.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82272067,81974386,M-0696,and 82273486)Natural Science Foundation of Hunan Province(Nos.2022JJ80052,2024JJ6596)the Innovation Fund for Postgraduate Students of Central South University(No.2023ZZTS0841)。
文摘Colorectal cancer(CRC)is one of the most prevalent malignant tumors worldwide,exhibiting high morbidity and mortality.Lack of efficient tools for early diagnosis and surgical resection guidance of CRC have been a serious threat to the long-term survival rate of the CRC patients.Recent studies have shown that relative higher viscosity was presented in tumor cells compared to that in normal cells,leading to viscosity as a potential biomarker for CRC.Herein,we reported the development of a series of novel viscosity-sensitive and mitochondria-specific fluorescent probes(HTB,HTI,and HTP)for CRC detection.Among them,HTB showed high sensitivity,minimal background interference,low cytotoxicity,and significant viscous response capability,making it an ideal tool for distinguishing colorectal tumor cells from normal cells.Importantly,we have successfully utilized HTB to visualize in a CRC-cells-derived xenograft(CDX)model,enriching its medical imaging capacity,which laid a foundation for further clinical translational application.
基金supported by the Zhejiang Provincial Natural Science Foundation of China(LY24H300001)the Medical and Health Research Project of Zhejiang Province(KY202302130009)National Health Service Research Project(WKZX2024CX501205).
文摘Objectives:Triphenylphosphine(TPP)and Doxorubicin(DOX)were conjugated to obtain Triphenylphosphine-Doxorubicin(TPP-DOX),which was applied in tumor cells for enhancement of DOX in mitochondria targeting.The study focused on investigating the anti-tumor effect of TPP-DOX in combination with radiotherapy throughout in vitro and in vivo studies.Methods:TPP-DOX was synthesized using the carbodiimide method.In vitro experiments were conducted with 4T1 cells(mouse breast cancer cell line)to assess apoptosis induction,mitochondrial targeting,reactive oxygen species(ROS)production,and mitochondrial membrane potential.The research evaluates the effects of TPP-DOX,DOX,and their combinations with radiotherapy.A nude mouse tumor heterograft model was established to investigate the synergistic effect of TPP-DOX and radiotherapy.Results:TPP-DOX was successfully synthesized and scrupulously verified.In vitro experiments showed that compared to DOX,TPP-DOX exhibited enhanced tumor cytotoxicity,improved cellular uptake in 4T1 cells,and increased apoptosis induction.Combined with radiotherapy,TPP-DOX promoted mitochondrial ROS production,reduced mitochondrial membrane potential,and amplified its anti-tumor effect.In vivo experiment confirmed that TPP-DOX combined with radiotherapy exhibited superior anti-tumor activity,promoted tumor tissue apoptosis,inhibited tumor angiogenesis,and showed a favorable in vivo safety profile.Conclusion:The study confirmed that when combined with radiotherapy,TPP-DOX promoted tumor cell apoptosis,and effectively enhanced the anti-tumor effect.In sensitive cells,TPP-DOX demonstrates comparable efficacy to DOX when combined with radiotherapy.TPP-DOX holds significant potential for a broader spectrum of applications and emerges as a valuable candidate for clinical application.These findings provide a promising and efficient therapeutic strategy for tumor treatment with improved efficacy and safety.
基金supported by the Natural Sci-ence Foundation of Fujian Province(No.2021J011374)the Science and Technology Program of Guangzhou(No.202002030486)the Science and Technology Project of Guangdong Province(No.2018B090944002).
文摘Mitochondria are well-acknowledged as ideal targets for tumor therapy due to their important role in energy supply and cellular signal regulation.Mitochondria-specific photosensitizers have been reported to be critical for inducing cell apoptosis.Two-photon fluorescence imaging provides a new technique for delineating biological structures and activities in deep tissues.Herein,we developed a new aggregation-induced emission(AIE)active photosensitizer by attaching a pyridinium group for mitochondrial target-ing.The rationally designed photosensitizer(TTTP)exhibited excellent photophysical properties,good biocompatibility,reactive oxygen species(ROS)stimulation ability,anticancer efficacy,and two-photon imaging properties.TTTP was highly taken up by cells and accumulated specifically in mitochondria but was selectively cytotoxic to cancer cells.Under light irradiation,the generation of ROS was significantly boosted,leading to actively induced apoptosis.The in vivo tumor photodynamic therapeutic efficacy of TTTP showed significant inhibition of tumor growth.Furthermore,the underlying mechanism of TTTP tu-mor suppression revealed that the apoptosis agonist Bax was markedly up-regulated while the antagonist Bcl-xL was down-regulated.This research provides a potential mitochondrial-targeted phototherapeutic agent for effective therapy and two-photon fluorescence imaging.
基金supported by the National Natural Science Foundation of China (Nos. 21877035 and 21977028)Research Foundation of Education Bureau of Hunan Province (No. 18B004)。
文摘Homocysteine(Hcy), cysteine(Cys) and glutathione(GSH) play crucial roles in redox homeostasis during mitochondria functions. Simultaneous differentiation and visualization of mitochondrial biothiols dynamics are significant for understanding cell metabolism and their related diseases. Herein, a multisitebinding fluorescent probe(MCP) was developed for simultaneous sensing of mitochondrial Cys, GSH and Hcy from three fluorescence channels for the first time. This novel probe exhibited rapid fluorescence turn-on, good water-solubility, high selectivity and large spectral separation for discriminating Cys, GSH and Hcy with 131-, 96-, 748-fold fluorescence increasement at 471, 520, 567 nm through different excitation wavelengths, respectively. Importantly, this probe was successfully applied to simultaneous monitoring of mitochondrial Cys, GSH, and Hcy in live cells and zebrafish from three fluorescence channels,promoting the understanding of the functions of Hcy, Cys and GSH.
基金the National Natural Science Foundation of China (Nos. 21775096, 22074084)One Hundred People Plan of Shanxi Province, Shanxi Province "1331 Project" Key Innovation Team Construction Plan Cultivation Team (No. 2018-CT-1)+4 种基金2018 Xiangyuan County Solid Waste Comprehensive Utilization Science and Technology Project (No. 2018XYSDJS-05)the Shanxi Province Foundation for Selected (2019), Innovative Talents of Higher Education Institutions of Shanxi, Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi (No. 2019L0031)Key R&D Program of Shanxi Province (No. 201903D421069)the Shanxi Province Science Foundation (No. 201901D111015)Scientific Instrument Center of Shanxi University (No. 201512)。
文摘Mitochondria is the main organelle for the production of reactive sulfur species(RSS), such as homocysteine(Hcy), cysteine(Cys), glutathione(GSH) and sulfur dioxide(SO_(2)). These compounds participate in a large number of physiological processes and play an extremely important role in maintaining the balance of life systems. Abnormal concentration and metabolism are closely related to many diseases. Due to their similarities in chemical properties, it is challenging to develop a single fluorescent probe to distinguish them simultaneously. Here, we synthesized the probe PI-CO–NBD with three fluorophores, NBD-Cl and benzopyranate as the reaction sites of GSH/Cys/Hcy and SO_(2), respectively. Three biothiols all could cleavage ether bond to release benzopyrylium and coumarin moiety, which emitted red and blue fluorescence,but Cys/Hcy also could do intramolecular rearrangement after nucleophilic substitution, resulting in yellow fluorescence. Thus the probe can distinguish Cys/Hcy and GSH. Subsequently, only SO_(2)could quench red fluorescence by adding C=C of benzopyrylium. The probe also could localize well in mitochondria by oxonium ion for all kinds of cells. The probe not only could detect above sulfur-containing active substances of intracellular and extracellular but also monitor the level of them under oxidative stress and apoptosis process in living cells and zebrafish.
基金supported by the National Natural Science Foundation of China(82173657,22077030,22271092)the support from the Institute of Fudan University-Quzhou。
文摘Multiple signaling molecules work together in mitochondria to mediate complex physiological processes.However,most current fluorescent probes lack of ability to clarify the function of these actives in mitochondria due to their non-specific binding with analytes outside mitochondria.In this study,we designed an on-demand light-activated mitochondria-targeted fluorescent probe to observe in situ fluctuations in mitochondrial esterase.The designed probe has a natural yellow fluorescence that monitors entry into the mitochondria and maintains nonfluorescent responsiveness to esterase during cellular delivery.Following the enrichment of the probe in mitochondria,on-demand photoactivation only at the required mitochondrial location resulted in a remarkable emission response to the esterase with red fluorescence at 700 nm.Precise spatiotemporal recognition of esterase in mitochondria is successfully achieved by activating the in situ fluorescence response of esterase by light irradiation.This work provides a new strategy for the study of esterase-related diseases.
基金supported by the Guangxi Science and Technology Base and Talent Special Project(Grant No.GuikeAD19254003)the National Natural Science Fund of China(Grant No.81972120).
文摘Excessive reactive oxygen species(ROS)-induced mitochondrial damage has impact on osteoarthritis(OA).Nanozyme mimics as natural enzyme alternatives to scavenge excessive ROS has offered a promising strategy for OA therapy.Herein,we reported a novel mitochondrial-targeting Mn_(3)O_(4)/UIO-TPP nanozyme using metal-organic frameworks with loaded Mn_(3)O_(4)as the enzyme-like active core combining mitochondria-targeting triphenylphosphine(TPP)groups to serve as ROS scavengers for therapy of OA.With sequential catalysis of superoxide dismutase-like,catalase(CAT)-like,and hydroxyl radical(·OH)scavenging potentials,the nanozyme can target mitochondria by crossing subcellular barriers to effectively eliminate ROS to restore mitochondrial function and inhibit inflammation and chondrocyte apoptosis.It also has favorable biocompatibility and biosafety.Based on anterior cruciate ligament transection-induced OA joint models,this mitochondrial-targeting nanozyme effectively mitigated the inflammatory response with the Pelletier score reduction of 49.9%after 8-week therapy.This study offers a prospective approach to the design of nanomedicines for ROS-related diseases.
基金supported by the National Natural Science Foundation of China(Nos.21971041 and 22001039)the Natural Science Foundation of Fujian Province(No.2020J01447).
文摘Developme nt of subcellular orga nelle-targeted bioimagi ng probes is of great imports nee in the field of early detection of diseases and exploring the behaviors of subcellular organelles.Herein,we present a triphenyIphosphonium functionalized conjugated macrocyclic tetramaleimide(TPP-CMT)as a mitochondrial-targeting bioimaging probe.The core of TPP-CMT is obtained by connecting two pyrenes and two benzenes through four maleimides.This unique structure endows TPP-CMT with exceptional far red/near-i nfirared aggregati on-induced emissi on(FR/NIR-AIE)characteristics.TPP-CMT is an excelle nt fluoresce nt emitter in most solve nts and eve n in solid states.The qua ntum yield of TPP-CMT was higher tha n 27% when dissolved in comm on middle-polarity orga nic solve nt and this value remained at 28.2% in its solid state.The in troducti on of four triphe ny Iphosph onium on maleimide positions endows TPP-CMT with mitochondrial-targeting ability.Thanks to the FR/NIR-AIE characteristics and the mitochondri-al-targeti ng ability,this well-desig ned fluoresce nt probe was successfully employed for mitochondrial targeti ng bioimaging of HeLa and HepG2 cells.
基金financially supported by the Shanghai 2020 “Science and Technology Innovation Action Plan” Social Development Science and Technology Research Project(No.20dz1203600)the Fundamental Research Funds for the Central Universities,and the Open Funds for Characterization of Tongji University.
文摘Nicotinamide adenine dinucleotide (NAD+/NADH) pools homeostasis is recognized as an Achilles’ Heel in tumor metabolism reprogramming. However, mitochondria can enable cancer cells to overcome NADH exhaustion by providing NAD+ precursors and/or intermediates, thus promoting their survival rate and potentially driving uncontrollable proliferation. Here, a synergistic intervention NAD+/NADH homeostasis and mitochondrial metabolism strategy with magnetic resonance imaging (MRI)/photoacoustic imaging (PAI) are developed to address grand challenge of metabolic reprogramming for antitumor bioenergetic therapy. A mitochondrial-targeted cascade amplification nanoplatform ([β-MQ]TRL), triggered by NAD(P)H: quinone oxidoreductase-1 (NQO1), can enable a continuous depletion of cytosol NADH until cell death. The end-product, hydrogen peroxide (H_(2)O_(2)), can be further catalytically converted to higher toxic ·OH in proximity to mitochondria based on [β-MQ]TRL mediated Fenton-like reaction, hijacking tumorigenic energy sources and leading to mitochondrial dysfunction. Additionally, the mild thermal ablation enabled by [β-MQ]TRL further amplifies this cascade reaction to effectively prevent tumor metastasis and recurrence. This synchronous intervention strategy with MRI/PAI establishes unprecedented efficiency in antitumor bioenergetic therapy in vivo, which shows excellent promise for clinical application.
