Cu2-x S nanocrystals(NCs), characterized by low cost, low toxicity, high stability and high photothermal conversion efficiency, provide promising platforms as photothermal agents. Herein, a novel twostep synthesis has...Cu2-x S nanocrystals(NCs), characterized by low cost, low toxicity, high stability and high photothermal conversion efficiency, provide promising platforms as photothermal agents. Herein, a novel twostep synthesis has been developed for Cu7S4 nanocrystals with hollow structure using the as-prepared copper nanoparticles as starting a solid precursor followed by hot-injection of sulfide source.The Cu7S4 NCs exhibit intense absorption band at Near-infrared(NIR) wavelengths due to localized surface plasmon resonance(LSPR)mode, which can effectively convert 980 nm-laser energy into heat.Moreover, the localized high temperature created by Cu7S4 NCs under NIR irradiation could result in efficient photothermal ablation(PTA) of cancer cells in vivo, demonstrating a novel and promising photothermal nanomaterials.展开更多
High-oleic peanuts has been recognized by processing sectors,seed sellers and consumers for their longer shelf life,longer seed life and mutiple healthe benefits.High oleate is becoming a requisite for varietal releas...High-oleic peanuts has been recognized by processing sectors,seed sellers and consumers for their longer shelf life,longer seed life and mutiple healthe benefits.High oleate is becoming a requisite for varietal releases in many peanut breeding programs at present.To select desirable parents for high-oleic peanut breeding,the study was conducted to evaluate the combining ability of 5 high-oleic donors from our research team,based on quality of individual single seeds.General combining ability was significant for oleic,linoleic,stearic and palmitic acid,oil and protein,while specific combining ability was significant for the traits except oil.Among them,oil content was found to be conditioned solely by additive gene actions,and for other quality traits,additive gene effects were more important than non-additive gene effects.High-oleic CTW and normal-oleic Xiaojingsheng were selected as the best general combiners for peanut oleic acid improvement.Narrow-sense heritability was high for quality traits other than protein,suggesting that there was high potential for genetic improvement in these traits.展开更多
Extracellular matrix(ECM)undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored.Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo^(+)self-assemb...Extracellular matrix(ECM)undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored.Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo^(+)self-assembly composed of azobenzene derivatives(Azo^(+))stacked via cation-πinteractions and stabilized with RGD ligand-bearing poly(acrylic acid).Near-infrared-upconverted-ultraviolet light induces cis-Azo^(+)-mediated inflation that suppresses cation-πinteractions,thereby inflating liganded self-assembly.This inflation increases nanospacing of“closely nanospaced”ligands from 1.8 nm to 2.6 nm and the surface area of liganded selfassembly that facilitate stem cell adhesion,mechanosensing,and differentiation both in vitro and in vivo,including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo^(+)molecules and loaded molecules.Conversely,visible light induces trans-Azo^(+)formation that facilitates cation-πinteractions,thereby deflating self-assembly with“closely nanospaced”ligands that inhibits stem cell adhesion,mechanosensing,and differentiation.In stark contrast,when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly,the surface area of“distantly nanospaced”ligands increases,thereby suppressing stem cell adhesion,mechanosensing,and differentiation.Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified.This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.展开更多
The majority of atherothrombotic events (e.g., cerebral or myocardial infarction) often occur as a result of plaque rupture or erosion in the carotid, and thereby it is urgent to assess plaque vulnerability and predic...The majority of atherothrombotic events (e.g., cerebral or myocardial infarction) often occur as a result of plaque rupture or erosion in the carotid, and thereby it is urgent to assess plaque vulnerability and predict adverse cerebrovascular events. However, the monitoring evolution from stable plaque into life-threatening high-risk plaque in the slender carotid artery is a great challenge, due to not enough spatial resolution for imaging the carotid artery based on most of reported fluorescent probes. Herein, copolymerizing with the small molecules of acceptor-donor-acceptor-donor-acceptor (A-D-A′-D-A) and the electron-donating units (D′), the screened second near-infrared (NIR-II) nanoprobe presents high quantum yield and good stability, so that it enables to image slender carotid vessel with enough spatial resolution. Encouragingly, NIR-II nanoprobe can effectively target to intraplaque macrophage, meanwhile distinguishing vulnerable plaque in carotid atherosclerosis in living mice. Moreover, the NIR-II nanoprobe can dynamically monitor the fresh bleeding spots in carotid plaque, indicating the increased risk of plaque instability. Besides, magnetic resonance imaging is integrated with NIR-II fluorescence imaging to provide contrast for subtle structure (e.g., narrow lumen and lipid pool), via incorporating ultrasmall superparamagnetic iron oxide into the NIR-II nanoprobe. Thus, such hybrid NIR-II/magnetic resonance imaging multimodal nanoprobe provides an effective tool for assessing carotid plaque burden, selecting high-risk plaque, and imaging intraplaque hemorrhage, which is promising for reducing cerebral/ myocardial infarction-associated morbidity and mortality.展开更多
Local hypoxia in solid tumors often results in resistance to radiotherapy （RT）, in which oxygen is an essential element for enhancing DNA damage caused by ionizing radiation. Herein, we developed gold@manganese diox...Local hypoxia in solid tumors often results in resistance to radiotherapy （RT）, in which oxygen is an essential element for enhancing DNA damage caused by ionizing radiation. Herein, we developed gold@manganese dioxide （Au@MnO2） core-shell nanoparticles with a polyethylene glycol （PEG） coating as a novel radiosensitizing agent to improve RT efficacy during cancer treatment. In this Au@MnO2 nanostructure, while the gold core is a well-known RT sensitizer that interacts with X-rays to produce charged particles for improved cancer killing under RT, the MnO2 shell may trigger the decomposition of endogenous H2O2 in the tumor microenvironment to generate oxygen and overcome hypoxiaassociated RT resistance. As demonstrated by both in vitro and in vivo experiments, Au@MnO2-PEG nanoparticles acted as effective radiosensitizers to remarkably enhance cancer treatment efficacy during RT. Moreover, no obvious side effects of Au@MnO2-PEG were observed in mice. Therefore, our work presents a new type of radiosensitizer with potential for enhanced RT treatment of hypoxic tumors.展开更多
Bioorthogonal cleavage reaction-triggered prodrug activation by the pretargeted methods can achieve accurate cancer therapy.However,the click and release efficiency of these methods in vivo is limited by the space-tim...Bioorthogonal cleavage reaction-triggered prodrug activation by the pretargeted methods can achieve accurate cancer therapy.However,the click and release efficiency of these methods in vivo is limited by the space-time dislocation of bioorthogonal prodrug-trigger pairs within the tumor area,caused by their asynchronous administration and inconsistent accumulation for most delivery systems.We herein created a nanovoid-confinement and click-activated(NCCA)core–shell nanoreactor by incorporating prodrugs within zeolitic imidazolate framework-90(ZIF-90)as core and coating tetrazine-based covalent organic framework(COF)as shell.After surface modification of aptamer polymer,the NCCA nanoreactor enabled the sufficient delivery of photodynamic prodrugs within tumor.Notably,the core of ZIF-90 was decomposed by tumor acidic environment,inducing the high-efficiency activation of photodynamic prodrugs via nanoconfined bioorthogonal reaction with tetrazine-based COF shell.As a result,such photodynamic agents are efficiently and safely accumulated into tumor and specifically activated for precise photodynamic therapy of cancer cells and tumor bearing mice with minimizing toxic side effect.Taken together,such NCCA nanoreactor clearly demonstrates the critical feasibility to realize the synchronous delivery of both prodrugs and triggers for precise treatment,which most of delivery systems are not able to afford.展开更多
Though imaging-guided multimodal therapy has been demonstrated as an effective strategy to improve cancer diagnosis and therapy,challenge remains as to simplify the sophisticated synthesis procedure for the correspond...Though imaging-guided multimodal therapy has been demonstrated as an effective strategy to improve cancer diagnosis and therapy,challenge remains as to simplify the sophisticated synthesis procedure for the corresponding nanoagents.Herein,an insitu one-step reduction-encapsulated method has been reported,for the first time,to synthesize multicore-shell polydopaminecoated Ag nanoparticles(AgNPs@PDA)as a cancer theranostic agent,integrating amplified photoacoustic imaging,enhanced photothermal therapy,and photothermal promoted dual tumor microenvironment-coactivated chemodynamic therapy.The photoacoustic signal and the photothermal conversion efficiency of AgNPs@PDA nanosystem present a 6.6-and 4.2-fold enhancement compared to those of M-AgNPs-PDA(simply mixing PDA and AgNPs)derived from the increased interface heat transfer coefficient and the stronger near-infrared absorption.Importantly,AgNPs@PDA coactivated by dual tumor microenvironment(TME)enables controllable long-term release of hydroxyl radicals(·OH)and toxic Ag+,which can be further promoted by near-infrared light irradiation.Moreover,the high efficiency of AgNPs@PDA nanosystem with prominent photoacoustic imaging-guided synergistic photothermal-chemodynamic cancer treatment is also found in in vitro and in vivo studies.As a special mention,the formation mechanism of the one-step synthesized multicore-shell nanomaterials is systematically investigated.This work provides a much simplified one-step synthesis method for the construction of a versatile nanoplatform for cancer theranostics with high efficacy.展开更多
For chemotherapy, drug delivery systems often suffer from the inefficient drug loading capability, which usually cause systems toxicity and extra burden to excrete carrier itself. Moreover, the cancer therapeutic effi...For chemotherapy, drug delivery systems often suffer from the inefficient drug loading capability, which usually cause systems toxicity and extra burden to excrete carrier itself. Moreover, the cancer therapeutic efficacy is also greatly limited by the specificity of tumor microenvironment for reactive oxygen species(ROS) based cancer therapeutic strategy(e.g., chemodynamic therapy). Herein, we have developed metal-drug coordination nanoplatform that can not only be responsive to tumor microenvironment but also modulate it, so as to achieve efficient treatment of cancer. Excitingly, by employing small molecule drug(6-thioguanine) as ligand copper ions, we achieve a high drug loading rate(60.1%) and 100% of utilization of metal-drug coordination nanoplatform(Cu-TG). Interestingly, Cu-TG possessed high-efficiently horseradish peroxidase-like, glutathione peroxidase-like and catalase-like activity. Under the tumor microenvironment, Cu-TG exhibited the self-reinforcing circular catalysis that is able to amplify the cellular oxidative stress, inducing notable cancer cellular apoptosis. Moreover, Cu-TG could be activated with glutathione(GSH) and facilitated for GSH triggered 6-TG release, higher selective therapeutic effect toward cancer cells, and GSH activated T1 weight-magnetic resonance imaging. Based on the above properties, Cu-TG exhibited magnetic resonance imaging(MRI) guiding, efficient and synergistic combination of chemodynamic and chemotherapy with self-reinforcing therapeutic outcomes in vivo.展开更多
For cancer therapy,drug delivery systems are often limited by insufficient drug loading capacity,which usually results in systemic toxicity and heavy metabolic burden to excrete the carriers.Herein,we reported a“one-...For cancer therapy,drug delivery systems are often limited by insufficient drug loading capacity,which usually results in systemic toxicity and heavy metabolic burden to excrete the carriers.Herein,we reported a“one-pot”method for constructing metal(Mn^(2+))–fluorouracil(FU)-coordinated nanotheranostics(Mn-FU)by self-assembly of FU(as bridging ligands)and Mn^(2+)(as metal nodes)through Mn–N/O coordination interactions.Importantly,owing to the effective coordination between Mn and FU,Mn-FU exhibits high drug loading efficacy(47.7 wt%),encapsulation efficacy(82.6%),and relatively large yield(1 g/pot).In acidic tumor microenvironments,efficient release of FU and Mn^(2+)is realized because of nitrogen protonation.The released FU and Mn^(2+)from Mn-FU are used for chemotherapy and turn on magnetic resonance imaging(MRI),respectively,achieving MRI-correlated drug release.After PEG modification,Mn-FU displays high tumor homing ability via enhanced permeability and retention effects and quick renal clearance owing to the disassembly in acidic biological conditions.As a result,Mn-FU substantially enhances the synergistic effects of chemoradiotherapy.Meanwhile,the systemic toxic side effects of free FU-based chemoradiotherapy were greatly reduced through this nanotheranostic.Our strategy offers a facile way to construct metallodrug nanotheranostics for efficient cancer theranostics.展开更多
Colon cancer is the third most common malignancy and the fourth most prevalent cause of death worldwide.Unfortunately,current cancer treatment approaches suffer from low specificity toward colon cancers and lack of fa...Colon cancer is the third most common malignancy and the fourth most prevalent cause of death worldwide.Unfortunately,current cancer treatment approaches suffer from low specificity toward colon cancers and lack of facile imagingmethod to monitor a real-time therapeutic process,usually resulting in severe toxicity to normal tissues.展开更多
基金financially supported by the National Natural Science Foundation of China (Grant Nos.21171035 and 51302035)the Key Grant Project of Chinese Ministry of Education (Grant No.313015)+7 种基金the PhD Programs Foundation of the Ministry of Education of China (Grant Nos.20110075110008 and 20130075120001)the National 863 Program of China (Grant No.2013AA031903)the Science and Technology Commission of Shanghai Municipality (Grant No.13ZR1451200)the Fundamental Research Funds for the Central Universitiesthe Hong Kong Scholars Programthe Program for Changjiang Scholars and Innovative Research Team in University (Grant No. IRT1221)the Shanghai Leading Academic Discipline Project (Grant No. B603)the Program of Introducing Talents of Discipline to Universities (No. 111-2-04)
文摘Cu2-x S nanocrystals(NCs), characterized by low cost, low toxicity, high stability and high photothermal conversion efficiency, provide promising platforms as photothermal agents. Herein, a novel twostep synthesis has been developed for Cu7S4 nanocrystals with hollow structure using the as-prepared copper nanoparticles as starting a solid precursor followed by hot-injection of sulfide source.The Cu7S4 NCs exhibit intense absorption band at Near-infrared(NIR) wavelengths due to localized surface plasmon resonance(LSPR)mode, which can effectively convert 980 nm-laser energy into heat.Moreover, the localized high temperature created by Cu7S4 NCs under NIR irradiation could result in efficient photothermal ablation(PTA) of cancer cells in vivo, demonstrating a novel and promising photothermal nanomaterials.
基金the financial support from Taishan Industry Leading Talents Special Fund(LJNY201808)Yantai Science and Technology Plan Project(2020XCZX046)+2 种基金Agricultural Scientific and Technological Innovation Project of Shandong Academy of Agricultural Sciences(CXGC2021A46,CXGC 2021A09)Corps Science and Technology Development Special Promotion Achievement Transformation Guidance Plan(2018BC012)China Agricultural Research System of MOF and MARA(CARS-13)to the first author.
文摘High-oleic peanuts has been recognized by processing sectors,seed sellers and consumers for their longer shelf life,longer seed life and mutiple healthe benefits.High oleate is becoming a requisite for varietal releases in many peanut breeding programs at present.To select desirable parents for high-oleic peanut breeding,the study was conducted to evaluate the combining ability of 5 high-oleic donors from our research team,based on quality of individual single seeds.General combining ability was significant for oleic,linoleic,stearic and palmitic acid,oil and protein,while specific combining ability was significant for the traits except oil.Among them,oil content was found to be conditioned solely by additive gene actions,and for other quality traits,additive gene effects were more important than non-additive gene effects.High-oleic CTW and normal-oleic Xiaojingsheng were selected as the best general combiners for peanut oleic acid improvement.Narrow-sense heritability was high for quality traits other than protein,suggesting that there was high potential for genetic improvement in these traits.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(No.RS-2023-00208427,2021R1I1A1A01046207,2021R1A2C2005418,2022R1A2C2005943,and 2022M3H4A1A03076638)supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(No.RS-2023-00271399 and RS-2023-00275654)+1 种基金supported by a Korea University Grant and KIST intramural programHAADF-STEM was conducted with the support of the Seoul center in Korea Basic Science Institute(KBSI).
文摘Extracellular matrix(ECM)undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored.Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo^(+)self-assembly composed of azobenzene derivatives(Azo^(+))stacked via cation-πinteractions and stabilized with RGD ligand-bearing poly(acrylic acid).Near-infrared-upconverted-ultraviolet light induces cis-Azo^(+)-mediated inflation that suppresses cation-πinteractions,thereby inflating liganded self-assembly.This inflation increases nanospacing of“closely nanospaced”ligands from 1.8 nm to 2.6 nm and the surface area of liganded selfassembly that facilitate stem cell adhesion,mechanosensing,and differentiation both in vitro and in vivo,including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo^(+)molecules and loaded molecules.Conversely,visible light induces trans-Azo^(+)formation that facilitates cation-πinteractions,thereby deflating self-assembly with“closely nanospaced”ligands that inhibits stem cell adhesion,mechanosensing,and differentiation.In stark contrast,when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly,the surface area of“distantly nanospaced”ligands increases,thereby suppressing stem cell adhesion,mechanosensing,and differentiation.Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified.This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.
基金the National Key R&D Program of China(2019YFA0210103)the National Natural Science Foundation of China(grants U21A20287,22234003,21977027,and 21974039)henzhen Science and Technology Program(JCYJ20210324140205013).
文摘The majority of atherothrombotic events (e.g., cerebral or myocardial infarction) often occur as a result of plaque rupture or erosion in the carotid, and thereby it is urgent to assess plaque vulnerability and predict adverse cerebrovascular events. However, the monitoring evolution from stable plaque into life-threatening high-risk plaque in the slender carotid artery is a great challenge, due to not enough spatial resolution for imaging the carotid artery based on most of reported fluorescent probes. Herein, copolymerizing with the small molecules of acceptor-donor-acceptor-donor-acceptor (A-D-A′-D-A) and the electron-donating units (D′), the screened second near-infrared (NIR-II) nanoprobe presents high quantum yield and good stability, so that it enables to image slender carotid vessel with enough spatial resolution. Encouragingly, NIR-II nanoprobe can effectively target to intraplaque macrophage, meanwhile distinguishing vulnerable plaque in carotid atherosclerosis in living mice. Moreover, the NIR-II nanoprobe can dynamically monitor the fresh bleeding spots in carotid plaque, indicating the increased risk of plaque instability. Besides, magnetic resonance imaging is integrated with NIR-II fluorescence imaging to provide contrast for subtle structure (e.g., narrow lumen and lipid pool), via incorporating ultrasmall superparamagnetic iron oxide into the NIR-II nanoprobe. Thus, such hybrid NIR-II/magnetic resonance imaging multimodal nanoprobe provides an effective tool for assessing carotid plaque burden, selecting high-risk plaque, and imaging intraplaque hemorrhage, which is promising for reducing cerebral/ myocardial infarction-associated morbidity and mortality.
基金supported by the National Key R&D Program of China(2019YFA0210100)the National Natural Science Foundation of China(22234003,U21A20287,22374045,and21890744)。
基金This work was partially supported by the National Basic Research Program of China （973 Program, Nos. 2014CB931900 and 2012CB932600）, National Natural Science Foundation of China （Nos. 81471716 and 31400861）, the National Natural Science Foundation of Jiangsu Province （No. BK20140320）, and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions （PAPD）.
文摘Local hypoxia in solid tumors often results in resistance to radiotherapy （RT）, in which oxygen is an essential element for enhancing DNA damage caused by ionizing radiation. Herein, we developed gold@manganese dioxide （Au@MnO2） core-shell nanoparticles with a polyethylene glycol （PEG） coating as a novel radiosensitizing agent to improve RT efficacy during cancer treatment. In this Au@MnO2 nanostructure, while the gold core is a well-known RT sensitizer that interacts with X-rays to produce charged particles for improved cancer killing under RT, the MnO2 shell may trigger the decomposition of endogenous H2O2 in the tumor microenvironment to generate oxygen and overcome hypoxiaassociated RT resistance. As demonstrated by both in vitro and in vivo experiments, Au@MnO2-PEG nanoparticles acted as effective radiosensitizers to remarkably enhance cancer treatment efficacy during RT. Moreover, no obvious side effects of Au@MnO2-PEG were observed in mice. Therefore, our work presents a new type of radiosensitizer with potential for enhanced RT treatment of hypoxic tumors.
基金supported by the National Key R&D Program of China(No.2019YFA0210103)the National Natural Science Foundation of China(No.21974039)+3 种基金China Postdoctoral Science Foundation(Nos.2020TQ0092 and 2020M682537)the Science and Technology Innovation Program of Hunan Province(No.2020RC2019)the Special Funds for the Construction of Innovative Provinces in Hunan Province(No.2019RS1031)the Opening Fund of Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research(Hunan Normal University),the Ministry of Education.
文摘Bioorthogonal cleavage reaction-triggered prodrug activation by the pretargeted methods can achieve accurate cancer therapy.However,the click and release efficiency of these methods in vivo is limited by the space-time dislocation of bioorthogonal prodrug-trigger pairs within the tumor area,caused by their asynchronous administration and inconsistent accumulation for most delivery systems.We herein created a nanovoid-confinement and click-activated(NCCA)core–shell nanoreactor by incorporating prodrugs within zeolitic imidazolate framework-90(ZIF-90)as core and coating tetrazine-based covalent organic framework(COF)as shell.After surface modification of aptamer polymer,the NCCA nanoreactor enabled the sufficient delivery of photodynamic prodrugs within tumor.Notably,the core of ZIF-90 was decomposed by tumor acidic environment,inducing the high-efficiency activation of photodynamic prodrugs via nanoconfined bioorthogonal reaction with tetrazine-based COF shell.As a result,such photodynamic agents are efficiently and safely accumulated into tumor and specifically activated for precise photodynamic therapy of cancer cells and tumor bearing mice with minimizing toxic side effect.Taken together,such NCCA nanoreactor clearly demonstrates the critical feasibility to realize the synchronous delivery of both prodrugs and triggers for precise treatment,which most of delivery systems are not able to afford.
基金the National Natural Science Foundation of China(Nos.21804036 and 21972039)the Science and Technology Project of Hunan Province(Nos.2020SK2014,2020RC3021,and 2020JJ3005).
文摘Though imaging-guided multimodal therapy has been demonstrated as an effective strategy to improve cancer diagnosis and therapy,challenge remains as to simplify the sophisticated synthesis procedure for the corresponding nanoagents.Herein,an insitu one-step reduction-encapsulated method has been reported,for the first time,to synthesize multicore-shell polydopaminecoated Ag nanoparticles(AgNPs@PDA)as a cancer theranostic agent,integrating amplified photoacoustic imaging,enhanced photothermal therapy,and photothermal promoted dual tumor microenvironment-coactivated chemodynamic therapy.The photoacoustic signal and the photothermal conversion efficiency of AgNPs@PDA nanosystem present a 6.6-and 4.2-fold enhancement compared to those of M-AgNPs-PDA(simply mixing PDA and AgNPs)derived from the increased interface heat transfer coefficient and the stronger near-infrared absorption.Importantly,AgNPs@PDA coactivated by dual tumor microenvironment(TME)enables controllable long-term release of hydroxyl radicals(·OH)and toxic Ag+,which can be further promoted by near-infrared light irradiation.Moreover,the high efficiency of AgNPs@PDA nanosystem with prominent photoacoustic imaging-guided synergistic photothermal-chemodynamic cancer treatment is also found in in vitro and in vivo studies.As a special mention,the formation mechanism of the one-step synthesized multicore-shell nanomaterials is systematically investigated.This work provides a much simplified one-step synthesis method for the construction of a versatile nanoplatform for cancer theranostics with high efficacy.
基金supported by the National Natural Science Foundation of China (51872088, 21977027, 21804039, 21675043, 21890744)。
文摘For chemotherapy, drug delivery systems often suffer from the inefficient drug loading capability, which usually cause systems toxicity and extra burden to excrete carrier itself. Moreover, the cancer therapeutic efficacy is also greatly limited by the specificity of tumor microenvironment for reactive oxygen species(ROS) based cancer therapeutic strategy(e.g., chemodynamic therapy). Herein, we have developed metal-drug coordination nanoplatform that can not only be responsive to tumor microenvironment but also modulate it, so as to achieve efficient treatment of cancer. Excitingly, by employing small molecule drug(6-thioguanine) as ligand copper ions, we achieve a high drug loading rate(60.1%) and 100% of utilization of metal-drug coordination nanoplatform(Cu-TG). Interestingly, Cu-TG possessed high-efficiently horseradish peroxidase-like, glutathione peroxidase-like and catalase-like activity. Under the tumor microenvironment, Cu-TG exhibited the self-reinforcing circular catalysis that is able to amplify the cellular oxidative stress, inducing notable cancer cellular apoptosis. Moreover, Cu-TG could be activated with glutathione(GSH) and facilitated for GSH triggered 6-TG release, higher selective therapeutic effect toward cancer cells, and GSH activated T1 weight-magnetic resonance imaging. Based on the above properties, Cu-TG exhibited magnetic resonance imaging(MRI) guiding, efficient and synergistic combination of chemodynamic and chemotherapy with self-reinforcing therapeutic outcomes in vivo.
基金This work was supported by National Key R&D Program of China(no.2019YFA0210103)National Natural Science Foundation of China(grant nos.51872088,21804039,21977027,and 21890744)the Fundamental Research Funds for the Central Universities.
文摘For cancer therapy,drug delivery systems are often limited by insufficient drug loading capacity,which usually results in systemic toxicity and heavy metabolic burden to excrete the carriers.Herein,we reported a“one-pot”method for constructing metal(Mn^(2+))–fluorouracil(FU)-coordinated nanotheranostics(Mn-FU)by self-assembly of FU(as bridging ligands)and Mn^(2+)(as metal nodes)through Mn–N/O coordination interactions.Importantly,owing to the effective coordination between Mn and FU,Mn-FU exhibits high drug loading efficacy(47.7 wt%),encapsulation efficacy(82.6%),and relatively large yield(1 g/pot).In acidic tumor microenvironments,efficient release of FU and Mn^(2+)is realized because of nitrogen protonation.The released FU and Mn^(2+)from Mn-FU are used for chemotherapy and turn on magnetic resonance imaging(MRI),respectively,achieving MRI-correlated drug release.After PEG modification,Mn-FU displays high tumor homing ability via enhanced permeability and retention effects and quick renal clearance owing to the disassembly in acidic biological conditions.As a result,Mn-FU substantially enhances the synergistic effects of chemoradiotherapy.Meanwhile,the systemic toxic side effects of free FU-based chemoradiotherapy were greatly reduced through this nanotheranostic.Our strategy offers a facile way to construct metallodrug nanotheranostics for efficient cancer theranostics.
基金supported by the National Key R&D Program of China(no.2019YFA0210103)the National Natural Science Foundation of China(grant nos.51872088,21804039,21977027,21890744,and 21890744)the Fundamental Research Funds for the Central Universities.
文摘Colon cancer is the third most common malignancy and the fourth most prevalent cause of death worldwide.Unfortunately,current cancer treatment approaches suffer from low specificity toward colon cancers and lack of facile imagingmethod to monitor a real-time therapeutic process,usually resulting in severe toxicity to normal tissues.
