Ferroptosis is a newly proposed type of programmed cell death,which has been associated with a variety of diseases including tumors.Researchers have thereby presented nanoplatforms to mediate ferroptosis for anti-canc...Ferroptosis is a newly proposed type of programmed cell death,which has been associated with a variety of diseases including tumors.Researchers have thereby presented nanoplatforms to mediate ferroptosis for anti-cancer therapy.However,the development of ferroptosis-based nanotherapeutics is generally hindered by the limited penetration depth in tumors,poor active pharmaceutical ingredient(API)loading content and the systemic toxicity.Herein,self-propelled ferroptosis nanoinducers composed of two endogenous proteins,glucose oxidase and ferritin,are presented to show enhanced tumor inhibition via ferroptosis while maintaining high API and biocompatibility.The accumulation of our proteomotors at tumor regions is facilitated by the active tumor-targeting effect of ferritin.The enhanced diffusion of proteomotors is then actuated by efficiently decomposing glucose into gluconic acid and H_(2)O_(2),leading to deeper penetration and enhanced uptake into tumors.Under the synergistic effect of glucose oxidase and ferritin,the equilibrium between reactive oxygen species and GSH is damaged,leading to lipid peroxidation.As a result,by inducing ferroptosis,our self-propelled ferroptosis nanoinducers exhibit enhanced tumor inhibitory effects.This work paves a way for the construction of a biocompatible anticancer platform with enhanced diffusion utilizing only two endogenous proteins,centered around the concept of ferroptosis.展开更多
Myocardial infarction(MI)is characterized by focal necrosis resulting from prolonged myocardial ischemia due to coronary artery obstruction.Vascular reconstruction following MI is crucial for improving cardiac functio...Myocardial infarction(MI)is characterized by focal necrosis resulting from prolonged myocardial ischemia due to coronary artery obstruction.Vascular reconstruction following MI is crucial for improving cardiac function and preventing recurrent infarction.This study investigates the interaction between macrophages and endothelial cells in angiogenesis mediated by nicotinamide mononucleotide(NMN)-induced secretion of macrophage-derived exosomes.We focus on the role of U2 small nuclear RNA auxiliary factor 1(U2af1)gene,a member of the splicing factor serine and arginine(SR)gene family,in the regulation of angiogenesis.Through cardiac ultrasound,Masson staining,2,3,5-triphenyltetrazolium chloride(TTC)staining,Microfil vascular perfusion,and platelet and endothelial cell adhesion molecule 1(CD31)immunofluorescence staining,extracellular vesicles from NMN-stimulated macrophages were shown to exert a protective effect in MI,with proteomic analysis identifying U2AF1 as a candidate protein involved in MI protection.Plasma U2AF1 levels were measured in 70 MI patients,revealing significantly lower levels in individuals with poor coronary collateral vessel(CCV;Rentrop scores 0–1)than in those with good CCV(Rentrop scores 2–3).In both myocardial and hindlimb ischemia mouse models,overexpression of endothelial cell-specific adenoviral overexpression U2AF1 promoted angiogenesis in the heart and hindlimbs and improved cardiac function after MI.Mechanistic studies demonstrated that U2AF1 regulates the alternative splicing(AS)of Yes1-associated transcriptional regulator(Yap1)gene,influencing post-MI angiogenesis and cardiac function recovery.Collectively,our clinical findings suggest that U2AF1 may serve as a therapeutic target for coronary collateral angiogenesis following MI.Given the low immunogenicity and high biosafety of exosomes,this study provides a foundational basis and translational potential for exosome-based therapies in MI treatment.展开更多
During the past several decades,positron emission tomography（PET） has been one of the rapidly growing areas of medical imaging;particularly,its applications in routine oncological practice have been widely recognize...During the past several decades,positron emission tomography（PET） has been one of the rapidly growing areas of medical imaging;particularly,its applications in routine oncological practice have been widely recognized.At present,^18F-fluorodeoxyglucose（^18F-FDG） is the most broadly used PET probe.However,^18F-FDG also suffers many limitations.Thus,scientists and clinicians are greatly interested in exploring and developing new PET imaging probes with high affinity and specificity.In this review,we briefly summarize the representative PET probes beyond ^18F-FDG that are available for patients imaging in three major clinical areas（oncology,neurology and cardiology）,and we also discuss the feasibility and trends in developing new PET probes for personalized medicine.展开更多
Whilst polymers have played a significant role in the development of modern society,a rapid growth of polymer waste is disadvantageously influencing communities and ecosystems across the world.Constructing a closed-lo...Whilst polymers have played a significant role in the development of modern society,a rapid growth of polymer waste is disadvantageously influencing communities and ecosystems across the world.Constructing a closed-loop life cycle of polymer materials is urgently in demand.Chemical recycling of polyesters,which can be recovered to the pristine monomers or transformed to other value-added products,has been considered as an appealing recycling approach to circular polymer economy and attracted enormous attention in the last several years.This review highlights some recent progress in the chemical recycling of diverse polyesters,including commercialized poly(lactic acid),poly(ε-caprolactone),poly(ethylene terephthalate),as well as various novel chemically recyclable polyesters and polycarbonates.Eventually,based on these technological developments,we discuss the remaining challenges and identify promising research opportunities,providing insights into future directions for achieving a genuine closed-loop polymer economy.展开更多
Bacterial biofilms can make traditional antibiotics impenetrable and even promote the development of antibiotic-resistant strains.Therefore,non-antibiotic strategies to effectively penetrate and eradicate the formed b...Bacterial biofilms can make traditional antibiotics impenetrable and even promote the development of antibiotic-resistant strains.Therefore,non-antibiotic strategies to effectively penetrate and eradicate the formed biofilms are urgently needed.Here,we demonstrate the development of selfpropelled biohybrid microrobots that can enhance the degradation and penetration effects for Pseudomonas aeruginosa biofilms in minimally invasive strategy.The biohybrid microrobots(CR@Alg)are constructed by surface modification of Chlamydomonas reinhardtii(CR)microalgae with alginate lyase(Alg)via biological orthogonal reaction.By degrading the biofilm components,the number of CR@Alg microrobots with fast-moving capability penetrating the biofilm increases by around 2.4-fold compared to that of microalgae.Massive reactive oxygen species are subsequently generated under laser irradiation due to the presence of chlorophyll,inherent photosensitizers of microalgae,thus triggering photodynamic therapy(PDT)to combat bacteria.Our algae-based microrobots with superior biocompatibility eliminate biofilm-infections efficiently and tend to suppress the inflammatory response in vivo,showing huge promise for the active treatment of biofilm-associated infections.展开更多
Enzyme-driven micro/nanomotors consuming in situ chemical fuels have attracted lots of attention for biomedical applications.However,motor systems composed by organism-derived organics that maximize the therapeutic ef...Enzyme-driven micro/nanomotors consuming in situ chemical fuels have attracted lots of attention for biomedical applications.However,motor systems composed by organism-derived organics that maximize the therapeutic efficacy of enzymatic products remain challenging.Herein,swimming proteomotors based on biocompatible urease and human serum albumin are constructed for enhanced antitumor therapy via active motion and ammonia amplification.By decomposing urea into carbon dioxide and ammonia,the designed proteomotors are endowed with self-propulsive capability,which leads to improved internalization and enhanced penetration in vitro.As a glutamine synthetase inhibitor,the loaded L-methionine sulfoximine further prevents the conversion of toxic ammonia into non-toxic glutamine in both tumor and stromal cells,resulting in local ammonia amplification.After intravesical instillation,the proteomotors achieve longer bladder retention and thus significantly inhibit the growth of orthotopic bladder tumor in vivo without adverse effects.We envision that the as-developed swimming proteomotors with amplification of the product toxicity may be a potential platform for active cancer treatment.展开更多
Insufficient therapeutic strategies for acute kidney injury(AKI)necessitate precision therapy targeting its pathogenesis.This study reveals the new mechanism of the marine-derived anti-AKI agent,piericidin glycoside S...Insufficient therapeutic strategies for acute kidney injury(AKI)necessitate precision therapy targeting its pathogenesis.This study reveals the new mechanism of the marine-derived anti-AKI agent,piericidin glycoside S14,targeting peroxiredoxin 1(PRDX1).By binding to Cys83 of PRDX1 and augmenting its peroxidase activity,S14 alleviates kidney injury efficiently in Prdx1-overexpression(Prdx1-OE)mice.Besides,S14 also increases PRDX1 nuclear translocation and directly activates the Nrf2/HO-1/NQO1 pathway to inhibit ROS production.Due to the limited druggability of S14 with low bioavailability(2.6%)and poor renal distribution,a pH-sensitive kidney-targeting dodecanaminechitosan nanoparticle system is constructed to load S14 for precise treatment of AKI.L-Serine conjugation to chitosan imparts specificity to kidney injury molecule-1(Kim-1)-overexpressed cells.The developed S14-nanodrug exhibits higher therapeutic efficiency by improving the in vivo behavior of S14 significantly.By encapsulation with micelles,the AUC_(0-t),half-life time,and renal distribution of S14 increase 2.5-,1.8-,and 3.1-fold,respectively.The main factors contributing to the improved druggability of S14 nanodrugs include the lower metabolic elimination rate and UDPglycosyltransferase(UGT)-mediated biotransformation.In summary,this study identifies a new therapeutic target for the marine-derived anti-AKI agent while enhancing its ADME properties and druggability through nanotechnology,thereby driving advancements in marine drug development for AKI.展开更多
Fluorescence imaging with high spatiotemporal resolution and sensitivity is employed for in vivo visualization and detection applications.Compared with visible light and the first near-infrared window(700-900 nm),the ...Fluorescence imaging with high spatiotemporal resolution and sensitivity is employed for in vivo visualization and detection applications.Compared with visible light and the first near-infrared window(700-900 nm),the second near-infrared window(1000-1700 nm)imaging has a lower auto-background fluorescence,deeper tissue penetration,and a higher signal-to-noise ratio,thus highlighting its broad prospects in the biomedical field.Currently,reported second near-infrared region probes include single-walled carbon nanotubes,rare-earth nanoparticles,quantum dots,metal materials,and organic molecular dyes.Multimodal imaging can overcome the limitations of single imaging and provide more comprehensive information on the anatomical structure,tissue composition,and cellular and molecular quantification of lesions to achieve multi-level visualization.Therefore,second near-infrared window nanoprobes must be engineered for multimodal imaging.Moreover,these nanoprobes can be actively targeted by modification with antibodies,peptides,nucleotides,or biofilms to obtain detailed and accurate information on biological systems.This review describes the active targeting capabilities of various second near-infrared window nanoprobes in multimodal imaging,diagnosis,and treatment of different diseases by carrying different ligands and the common features and future application prospects of second near-infrared window fluorescent nanoprobes with targeting ability.展开更多
Janus polymerization consists of anionic and cationic ring opening polymerizations(AROP and CROP)at the two ends of a single propagating polymer chain,followed by a self-triggered chain extension generating multiblock...Janus polymerization consists of anionic and cationic ring opening polymerizations(AROP and CROP)at the two ends of a single propagating polymer chain,followed by a self-triggered chain extension generating multiblock copolymers(MBCPs)in one step.In the contribution,Janus polymerization by Tm(OTf)_(3) or Er(OTf)_(3) catalyst with an epoxy initiator is applied to synthesize MBCPs of semi-crystalline poly(ε-caprolactone)(PCL)blocks from coordinated AROP and poly(1,3-dioxolane-co-ε-caprolactone)(P(DO-co-CL))blocks from CROP of DO with CL.Meanwhile,amorphous random copolymers[P(DO-r-CL)]are synthesized as control by employing other rare earth triflates[RE(OTf)_(3),RE=Y,Nd,Gd and Lu]as catalysts or in the absence of an initiator via CROP.On account of the distinguishable chemical structures and thermal properties between Janus MBCPs and cationic random copolymers,Janus features are confirmed including the CROP and AROP at a single propagating chain.The resultant amphiphilic copolymers self-assemble to nanoparticles in aqueous solution with designable diameters with the corresponding ratios of hydrophilic and hydrophobic seg-ments.MBCPs exhibit good shape memory properties with appropriate deformation temperature close to human body's,providing a prospect on the applications in biomedical devices.展开更多
Attributed to the miniaturized body size and active mobility,micro-and nanomotors(MNMs)have demonstrated tremendous potential for medical applications.However,from bench to bedside,massive efforts are needed to addres...Attributed to the miniaturized body size and active mobility,micro-and nanomotors(MNMs)have demonstrated tremendous potential for medical applications.However,from bench to bedside,massive efforts are needed to address critical issues,such as cost-effective fabrication,on-demand integration of multiple functions,biocompatibility,biodegradability,controlled propulsion and in vivo navigation.Herein,we summarize the advances of biomedical MNMs reported in the past two decades,with particular emphasis on the design,fabrication,propulsion,navigation,and the abilities of biological barriers penetration,biosensing,diagnosis,minimally invasive surgery and targeted cargo delivery.Future perspectives and challenges are discussed as well.This review can lay the foundation for the future direction of medical MNMs,pushing one step forward on the road to achieving practical theranostics using MNMs.展开更多
PINK1/Parkin-mediated mitophagy is an important process in selective removal of damaged mitochondria, in which translocation of Parkin to damaged mitochondria is recognized as an initiation step. At present, how the d...PINK1/Parkin-mediated mitophagy is an important process in selective removal of damaged mitochondria, in which translocation of Parkin to damaged mitochondria is recognized as an initiation step. At present, how the damaged mitochondria are selectively recognized and targeted by Parkin is not fully understood. Here we show that Miro2, an outer mitochondrial membrane protein, undergoes demultimerization from a tetramer to a monomer and alteration in mitochondrial localization upon CCCP treatment, suggesting a CCCP-induced realignment of Miro2. The realignment of Miro2 is tightly regulated by PINK1-mediated phosphorylation at Ser325/Ser430 and by Ca^2+binding to EF2 domain, which are both essential for the subsequent Parkin translocation. Interestingly, ablation of Miro2 in mouse causes delayed reticulocyte maturation, lactic acidosis and cardiac disorders. Furthermore, several Miro2 mutations found in the congenital lactic acidosis patients also disable its realignment and Parkin translocation. These findings reveal an important role of Miro2 to mediate Parkin translocation by sensing both depolarization and Ca^2+release from damaged mitochondria to ensure the accuracy of mitophagy.展开更多
基金supported by National Key Research and Development Program of China(No.2022YFA1206900)National Natural Science Foundation of China(Nos.22175083,82204415,51973241,22375224)GuangDong Basic and Applied Basic Research Foundation(No.2021A1515220187)。
文摘Ferroptosis is a newly proposed type of programmed cell death,which has been associated with a variety of diseases including tumors.Researchers have thereby presented nanoplatforms to mediate ferroptosis for anti-cancer therapy.However,the development of ferroptosis-based nanotherapeutics is generally hindered by the limited penetration depth in tumors,poor active pharmaceutical ingredient(API)loading content and the systemic toxicity.Herein,self-propelled ferroptosis nanoinducers composed of two endogenous proteins,glucose oxidase and ferritin,are presented to show enhanced tumor inhibition via ferroptosis while maintaining high API and biocompatibility.The accumulation of our proteomotors at tumor regions is facilitated by the active tumor-targeting effect of ferritin.The enhanced diffusion of proteomotors is then actuated by efficiently decomposing glucose into gluconic acid and H_(2)O_(2),leading to deeper penetration and enhanced uptake into tumors.Under the synergistic effect of glucose oxidase and ferritin,the equilibrium between reactive oxygen species and GSH is damaged,leading to lipid peroxidation.As a result,by inducing ferroptosis,our self-propelled ferroptosis nanoinducers exhibit enhanced tumor inhibitory effects.This work paves a way for the construction of a biocompatible anticancer platform with enhanced diffusion utilizing only two endogenous proteins,centered around the concept of ferroptosis.
基金supported by the National Natural Science Founda-tion of China(82370417,82330011,and U21A20339)the Science Fund for Distinguished Young Scholars of Heilongjiang Province(JQ2024H001)the Heilongjiang Provincial Postdoctoral Science Foundation(LBH-Z23212).
文摘Myocardial infarction(MI)is characterized by focal necrosis resulting from prolonged myocardial ischemia due to coronary artery obstruction.Vascular reconstruction following MI is crucial for improving cardiac function and preventing recurrent infarction.This study investigates the interaction between macrophages and endothelial cells in angiogenesis mediated by nicotinamide mononucleotide(NMN)-induced secretion of macrophage-derived exosomes.We focus on the role of U2 small nuclear RNA auxiliary factor 1(U2af1)gene,a member of the splicing factor serine and arginine(SR)gene family,in the regulation of angiogenesis.Through cardiac ultrasound,Masson staining,2,3,5-triphenyltetrazolium chloride(TTC)staining,Microfil vascular perfusion,and platelet and endothelial cell adhesion molecule 1(CD31)immunofluorescence staining,extracellular vesicles from NMN-stimulated macrophages were shown to exert a protective effect in MI,with proteomic analysis identifying U2AF1 as a candidate protein involved in MI protection.Plasma U2AF1 levels were measured in 70 MI patients,revealing significantly lower levels in individuals with poor coronary collateral vessel(CCV;Rentrop scores 0–1)than in those with good CCV(Rentrop scores 2–3).In both myocardial and hindlimb ischemia mouse models,overexpression of endothelial cell-specific adenoviral overexpression U2AF1 promoted angiogenesis in the heart and hindlimbs and improved cardiac function after MI.Mechanistic studies demonstrated that U2AF1 regulates the alternative splicing(AS)of Yes1-associated transcriptional regulator(Yap1)gene,influencing post-MI angiogenesis and cardiac function recovery.Collectively,our clinical findings suggest that U2AF1 may serve as a therapeutic target for coronary collateral angiogenesis following MI.Given the low immunogenicity and high biosafety of exosomes,this study provides a foundational basis and translational potential for exosome-based therapies in MI treatment.
文摘During the past several decades,positron emission tomography（PET） has been one of the rapidly growing areas of medical imaging;particularly,its applications in routine oncological practice have been widely recognized.At present,^18F-fluorodeoxyglucose（^18F-FDG） is the most broadly used PET probe.However,^18F-FDG also suffers many limitations.Thus,scientists and clinicians are greatly interested in exploring and developing new PET imaging probes with high affinity and specificity.In this review,we briefly summarize the representative PET probes beyond ^18F-FDG that are available for patients imaging in three major clinical areas（oncology,neurology and cardiology）,and we also discuss the feasibility and trends in developing new PET probes for personalized medicine.
基金support from the National Natural Science Foundation of China(22231008,52103001,and 22071167)the Natural Science Foundation of Jiangsu Higher Education Institutions of China(22KJA150005)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions is gratefully acknowledged.
文摘Whilst polymers have played a significant role in the development of modern society,a rapid growth of polymer waste is disadvantageously influencing communities and ecosystems across the world.Constructing a closed-loop life cycle of polymer materials is urgently in demand.Chemical recycling of polyesters,which can be recovered to the pristine monomers or transformed to other value-added products,has been considered as an appealing recycling approach to circular polymer economy and attracted enormous attention in the last several years.This review highlights some recent progress in the chemical recycling of diverse polyesters,including commercialized poly(lactic acid),poly(ε-caprolactone),poly(ethylene terephthalate),as well as various novel chemically recyclable polyesters and polycarbonates.Eventually,based on these technological developments,we discuss the remaining challenges and identify promising research opportunities,providing insights into future directions for achieving a genuine closed-loop polymer economy.
基金supported by National Key Research and Development Program of China(2022YFA1206900)Guangdong Basic and Applied Basic Research Foundation(2022A1515110659,China)National Natural Science Foundation of China(22175083 and 22375224).
文摘Bacterial biofilms can make traditional antibiotics impenetrable and even promote the development of antibiotic-resistant strains.Therefore,non-antibiotic strategies to effectively penetrate and eradicate the formed biofilms are urgently needed.Here,we demonstrate the development of selfpropelled biohybrid microrobots that can enhance the degradation and penetration effects for Pseudomonas aeruginosa biofilms in minimally invasive strategy.The biohybrid microrobots(CR@Alg)are constructed by surface modification of Chlamydomonas reinhardtii(CR)microalgae with alginate lyase(Alg)via biological orthogonal reaction.By degrading the biofilm components,the number of CR@Alg microrobots with fast-moving capability penetrating the biofilm increases by around 2.4-fold compared to that of microalgae.Massive reactive oxygen species are subsequently generated under laser irradiation due to the presence of chlorophyll,inherent photosensitizers of microalgae,thus triggering photodynamic therapy(PDT)to combat bacteria.Our algae-based microrobots with superior biocompatibility eliminate biofilm-infections efficiently and tend to suppress the inflammatory response in vivo,showing huge promise for the active treatment of biofilm-associated infections.
基金supported by the National Natural Science Foundation of China(22175083,51973241,31900567 and 82102051)the Guangzhou Basic and Applied Basic Research Foundation(202201011078)。
文摘Enzyme-driven micro/nanomotors consuming in situ chemical fuels have attracted lots of attention for biomedical applications.However,motor systems composed by organism-derived organics that maximize the therapeutic efficacy of enzymatic products remain challenging.Herein,swimming proteomotors based on biocompatible urease and human serum albumin are constructed for enhanced antitumor therapy via active motion and ammonia amplification.By decomposing urea into carbon dioxide and ammonia,the designed proteomotors are endowed with self-propulsive capability,which leads to improved internalization and enhanced penetration in vitro.As a glutamine synthetase inhibitor,the loaded L-methionine sulfoximine further prevents the conversion of toxic ammonia into non-toxic glutamine in both tumor and stromal cells,resulting in local ammonia amplification.After intravesical instillation,the proteomotors achieve longer bladder retention and thus significantly inhibit the growth of orthotopic bladder tumor in vivo without adverse effects.We envision that the as-developed swimming proteomotors with amplification of the product toxicity may be a potential platform for active cancer treatment.
基金supported by the Guangdong Local Innovation Team Program(2019BT02Y262,China)National Natural Science Foundation of China(U20A20101,82274002,22175083)+2 种基金Key-Area Research and Development Program of Guangdong Province(2023B1111050008,China)National Key Research and Development Program of China(2022YFA1206900,2023YFA0914200)Science and Technology Innovation Project of Guangdong Medical Products Administration(S2021ZDZ042,2023ZDZ06,2024ZDZ08,China).
文摘Insufficient therapeutic strategies for acute kidney injury(AKI)necessitate precision therapy targeting its pathogenesis.This study reveals the new mechanism of the marine-derived anti-AKI agent,piericidin glycoside S14,targeting peroxiredoxin 1(PRDX1).By binding to Cys83 of PRDX1 and augmenting its peroxidase activity,S14 alleviates kidney injury efficiently in Prdx1-overexpression(Prdx1-OE)mice.Besides,S14 also increases PRDX1 nuclear translocation and directly activates the Nrf2/HO-1/NQO1 pathway to inhibit ROS production.Due to the limited druggability of S14 with low bioavailability(2.6%)and poor renal distribution,a pH-sensitive kidney-targeting dodecanaminechitosan nanoparticle system is constructed to load S14 for precise treatment of AKI.L-Serine conjugation to chitosan imparts specificity to kidney injury molecule-1(Kim-1)-overexpressed cells.The developed S14-nanodrug exhibits higher therapeutic efficiency by improving the in vivo behavior of S14 significantly.By encapsulation with micelles,the AUC_(0-t),half-life time,and renal distribution of S14 increase 2.5-,1.8-,and 3.1-fold,respectively.The main factors contributing to the improved druggability of S14 nanodrugs include the lower metabolic elimination rate and UDPglycosyltransferase(UGT)-mediated biotransformation.In summary,this study identifies a new therapeutic target for the marine-derived anti-AKI agent while enhancing its ADME properties and druggability through nanotechnology,thereby driving advancements in marine drug development for AKI.
基金support by Scientific Research Foundation for Postdoctoral Heilongjiang Province of China(LBH-Q19037).
文摘Fluorescence imaging with high spatiotemporal resolution and sensitivity is employed for in vivo visualization and detection applications.Compared with visible light and the first near-infrared window(700-900 nm),the second near-infrared window(1000-1700 nm)imaging has a lower auto-background fluorescence,deeper tissue penetration,and a higher signal-to-noise ratio,thus highlighting its broad prospects in the biomedical field.Currently,reported second near-infrared region probes include single-walled carbon nanotubes,rare-earth nanoparticles,quantum dots,metal materials,and organic molecular dyes.Multimodal imaging can overcome the limitations of single imaging and provide more comprehensive information on the anatomical structure,tissue composition,and cellular and molecular quantification of lesions to achieve multi-level visualization.Therefore,second near-infrared window nanoprobes must be engineered for multimodal imaging.Moreover,these nanoprobes can be actively targeted by modification with antibodies,peptides,nucleotides,or biofilms to obtain detailed and accurate information on biological systems.This review describes the active targeting capabilities of various second near-infrared window nanoprobes in multimodal imaging,diagnosis,and treatment of different diseases by carrying different ligands and the common features and future application prospects of second near-infrared window fluorescent nanoprobes with targeting ability.
基金supported by the National Natural Science Foundationof China(No.21871232)。
文摘Janus polymerization consists of anionic and cationic ring opening polymerizations(AROP and CROP)at the two ends of a single propagating polymer chain,followed by a self-triggered chain extension generating multiblock copolymers(MBCPs)in one step.In the contribution,Janus polymerization by Tm(OTf)_(3) or Er(OTf)_(3) catalyst with an epoxy initiator is applied to synthesize MBCPs of semi-crystalline poly(ε-caprolactone)(PCL)blocks from coordinated AROP and poly(1,3-dioxolane-co-ε-caprolactone)(P(DO-co-CL))blocks from CROP of DO with CL.Meanwhile,amorphous random copolymers[P(DO-r-CL)]are synthesized as control by employing other rare earth triflates[RE(OTf)_(3),RE=Y,Nd,Gd and Lu]as catalysts or in the absence of an initiator via CROP.On account of the distinguishable chemical structures and thermal properties between Janus MBCPs and cationic random copolymers,Janus features are confirmed including the CROP and AROP at a single propagating chain.The resultant amphiphilic copolymers self-assemble to nanoparticles in aqueous solution with designable diameters with the corresponding ratios of hydrophilic and hydrophobic seg-ments.MBCPs exhibit good shape memory properties with appropriate deformation temperature close to human body's,providing a prospect on the applications in biomedical devices.
基金supported by the National Natural Science Foundation of China(Grant No.22175083,51973241,82001845,52072095,92163109 and 22193033)。
文摘Attributed to the miniaturized body size and active mobility,micro-and nanomotors(MNMs)have demonstrated tremendous potential for medical applications.However,from bench to bedside,massive efforts are needed to address critical issues,such as cost-effective fabrication,on-demand integration of multiple functions,biocompatibility,biodegradability,controlled propulsion and in vivo navigation.Herein,we summarize the advances of biomedical MNMs reported in the past two decades,with particular emphasis on the design,fabrication,propulsion,navigation,and the abilities of biological barriers penetration,biosensing,diagnosis,minimally invasive surgery and targeted cargo delivery.Future perspectives and challenges are discussed as well.This review can lay the foundation for the future direction of medical MNMs,pushing one step forward on the road to achieving practical theranostics using MNMs.
基金supported by the National Natural Science Foundation of China (91754204)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16010107)+5 种基金National Key Research and Development Program of China (2018YFA0108500, 2017YFC1001001)the National NaturalScience Foundation of China (81630078, 31670822, 31401151, 31570816, 81371415)the Natural Science Foundation of Beijing (5181001)CAS Strategic Priority Research Program (XDB14030300)the State Key Laboratory of Membrane Biologythe Key Laboratory of Genomic and Precision Medicine
文摘PINK1/Parkin-mediated mitophagy is an important process in selective removal of damaged mitochondria, in which translocation of Parkin to damaged mitochondria is recognized as an initiation step. At present, how the damaged mitochondria are selectively recognized and targeted by Parkin is not fully understood. Here we show that Miro2, an outer mitochondrial membrane protein, undergoes demultimerization from a tetramer to a monomer and alteration in mitochondrial localization upon CCCP treatment, suggesting a CCCP-induced realignment of Miro2. The realignment of Miro2 is tightly regulated by PINK1-mediated phosphorylation at Ser325/Ser430 and by Ca^2+binding to EF2 domain, which are both essential for the subsequent Parkin translocation. Interestingly, ablation of Miro2 in mouse causes delayed reticulocyte maturation, lactic acidosis and cardiac disorders. Furthermore, several Miro2 mutations found in the congenital lactic acidosis patients also disable its realignment and Parkin translocation. These findings reveal an important role of Miro2 to mediate Parkin translocation by sensing both depolarization and Ca^2+release from damaged mitochondria to ensure the accuracy of mitophagy.
