Rapid evolution and propagation of multidrug resistance among bacterial pathogens are outpacing the development of new antibiotics,but antimicrobial photodynamic therapy(aPDT)provides an excellent alternative.This tre...Rapid evolution and propagation of multidrug resistance among bacterial pathogens are outpacing the development of new antibiotics,but antimicrobial photodynamic therapy(aPDT)provides an excellent alternative.This treatment depends on the interaction between light and photoactivated sensitizer to generate reactive oxygen species(ROS),which are highly cytotoxic to induce apoptosis in virtually all microorganisms without resistance concern.When replacing light with low-frequency ultrasonic wave to activate sensitizer,a novel ultrasounddriven treatment emerges as antimicrobial sonodynamic therapy(aSDT).Recent advances in aPDT and aSDT reveal golden opportunities for the management of multidrug resistant bacterial infections,especially in the theranostic application where imaging diagnosis can be accomplished facilely with the inherent optical characteristics of sensitizers,and the generated ROS by aPDT/SDT cause broad-spectrum oxidative damage for sterilization.In this review,we systemically outline the mechanisms,targets,and current progress of aPDT/SDT for bacterial theranostic application.Furthermore,potential limitations and future perspectives are also highlighted.展开更多
Stanene(Sn)-based materials have been extensively applied in industrial production and daily life,but their potential biomedical application remains largely unexplored,which is due to the absence of the appropriate an...Stanene(Sn)-based materials have been extensively applied in industrial production and daily life,but their potential biomedical application remains largely unexplored,which is due to the absence of the appropriate and effective methods for fabricating Sn-based biomaterials.Herein,we explored a new approach combining cryogenic exfoliation and liquid-phase exfoliation to successfully manufacture two-dimensional(2D)Sn nanosheets(SnNSs).The obtained SnNSs exhibited a typical sheet-like structure with an average size of~100 nm and a thickness of~5.1 nm.After PEGylation,the resulting PEGylated SnNSs(SnNSs@PEG)exhibited good stability,superior biocompatibility,and excellent photothermal performance,which could serve as robust photothermal agents for multi-modal imaging(fluorescence/photoacoustic/photothermal imaging)-guided photothermal elimination of cancer.Furthermore,we also used first-principles density functional theory calculations to investigate the photothermal mechanism of SnNSs,revealing that the free electrons in upper and lower layers of SnNSs contribute to the conversion of the photo to thermal.This work not only introduces a new approach to fabricate 2D SnNSs but also establishes the SnNSs-based nanomedicines for photonic cancer theranostics.This new type of SnNSs with great potential in the field of nanomedicines may spur a wave of developing Sn-based biological materials to benefit biomedical applications.展开更多
The insistent demand for space-controllable delivery,which reduces the side effects of non-steroidal antiinflammatory drugs(NSAIDs),has led to the development of a new theranostics-based approach for anti-inflammatory...The insistent demand for space-controllable delivery,which reduces the side effects of non-steroidal antiinflammatory drugs(NSAIDs),has led to the development of a new theranostics-based approach for anti-inflammatory therapy.The current anti-inflammatory treatments can be improved by designing a drug delivery system responsive to the inflammatory site biomarker,hydrogen polysulfide(H_(2)S_(n)).Here,we report a noveltheranostic agent 1(TA1),consisting of three parts:H_(2)S_(n)-mediated triggering part,a two-photon fluorophore bearing mitochondria targeting unit(Rhodol-TPP),and anti-inflammatory COX inhibitor(indomethacin).In vitro experiments showed that TA1 selectively reacts with H_(2)S_(n)to concomitantly release both Rhodol-TPP and indomethacin.Confocal-microscopy imaging of inflammation-inducedlive cells suggested that TA1 is localized in the mitochondria where the H_(2)S_(n)is overexpressed.The TA1 reacted with H_(2)S_(n)in the endogenous and exogenous H_(2)S_(n)environments and in lipopolysaccharide treated inflammatory cells.Moreover,TA1 suppressed COX-2 level in the inflammatory-induced cells and prostaglandin E 2(PGE2)level in blood serum from inflammation-induced mouse models.In vivo experiments with inflammation-induced mouse models suggested that TA1 exhibits inflammation-site-elective drug release followed by significant therapeutic e ects,showing its function as a theranostic agent,capable of both anti-inflammatory therapy and precise diagnosis.Theranostic behavior of TA1 is highly applicable in vivo model therapeutics for the inflammatory disease.展开更多
Many studies have recently attempted to develop multifunctional nanoconstructs by integrating the superior fluores- cence properties of quantum dots （QD） with therapeutic capabilities into a single vesicle for cance...Many studies have recently attempted to develop multifunctional nanoconstructs by integrating the superior fluores- cence properties of quantum dots （QD） with therapeutic capabilities into a single vesicle for cancer theranostics. Liposome- quantum dot （L-QD） hybrid vesicles have shown promising potential for the construction of multifunctional nanoconstructs for cancer imaging and therapy. To fulfil such a potential, we report here the further functionalization of L-QD hybrid vesi- cles with therapeutic capabilities by loading anticancer drug doxorubicin （Dox） into their aqueous core. L-QD hybrid vesi- cles are first engineered by the incorporation of TOPO-capped, CdSe/ZnS QD into the lipid bilayers of DSPC：Chol：DSPE- PEG2000, followed by Dox loading using the pH-gradient technique. The loading efficiency of Dox into L-QD hybrid vesicles is achieved up to 97%, comparable to liposome control. All these evidences prove that the incorporation of QD into the lipid bilayer does not affect Dox loading through the lipid membrane of liposomes using the pH-gradient technique. Moreover, the release study shows that Dox release profile can be modulated simply by changing lipid composition. In conclusion, the Dox-loaded L-QD hybrid vesicles presented here constitute a promising multifunctional nanoconstruct capable of transporting combinations of therapeutic and diagnostic modalities.展开更多
Since the discovery of enzyme-like activity of Fe3O4 nanoparticles in 2007,nanozymes are becoming the promising substitutes for natural enzymes due to their advantages of high catalytic activity,low cost,mild reaction...Since the discovery of enzyme-like activity of Fe3O4 nanoparticles in 2007,nanozymes are becoming the promising substitutes for natural enzymes due to their advantages of high catalytic activity,low cost,mild reaction conditions,good stability,and suitable for large-scale production.Recently,with the cross fusion of nanomedicine and nanocatalysis,nanozyme-based theranostic strategies attract great attention,since the enzymatic reactions can be triggered in the tumor microenvironment to achieve good curative effect with substrate specificity and low side effects.Thus,various nanozymes have been developed and used for tumor therapy.In this review,more than 270 research articles are discussed systematically to present progress in the past five years.First,the discovery and development of nanozymes are summarized.Second,classification and catalytic mechanism of nanozymes are discussed.Third,activity prediction and rational design of nanozymes are focused by highlighting the methods of density functional theory,machine learning,biomimetic and chemical design.Then,synergistic theranostic strategy of nanozymes are introduced.Finally,current challenges and future prospects of nanozymes used for tumor theranostic are outlined,including selectivity,biosafety,repeatability and stability,in-depth catalytic mechanism,predicting and evaluating activities.展开更多
Theranostics is a concept that integrated imaging and therapy. As an emerging field, it embraces multiple techniques to arrive at an individualized treatment purpose. Indocyanine green(ICG) is a near infrared dye that...Theranostics is a concept that integrated imaging and therapy. As an emerging field, it embraces multiple techniques to arrive at an individualized treatment purpose. Indocyanine green(ICG) is a near infrared dye that has been approved by Food and Drug Administration(FDA) in USA for the use in indicator-dilution studies in humans. ICG nanoparticles(NPs) have attracted much attention for its potential applications in cancer theranostics. This review focuses on the preparation, application of ICG NPs for in vivo imaging(fluorescent imaging and photoacoustic imaging) and therapeutics(photothermal therapy, photodynamic therapy and photoacoustic therapy), and future directions based on recent developments in these areas. It is hoped that this review might provide new impetus to understand ICG NPs for cancer theranostics.展开更多
Natural enzymes usually suffer from high production cost,ease of denaturation and inactivation,and low yield,making them difficult to be broadly applicable.As an emerging type of artificial enzyme,nanozymes that combi...Natural enzymes usually suffer from high production cost,ease of denaturation and inactivation,and low yield,making them difficult to be broadly applicable.As an emerging type of artificial enzyme,nanozymes that combine the characteristics of nanomaterials and enzymes are promising alternatives.On the one hand,nanozymes have high enzyme-like catalytic activities to regulate biochemical reactions.On the other hand,nanozymes also inherit the properties of nanomaterials,which can ameliorate the shortcomings of natural enzymes and serve as versatile platforms for diverse applications.In this review,various nanozymes that mimic the catalytic activity of different enzymes are introduced.The achievements of nanozymes in different cancer diagnosis and treatment technologies are summarized by highlighting the advantages of nanozymes in these applications.Finally,future research directions in this rapidly developing field are outlooked.展开更多
MXenes,transition metal carbides and nitrides with graphene-like structures,have received considerable attention since their first discovery.On the other hand,Graphene has been extensively used in biomedical and medic...MXenes,transition metal carbides and nitrides with graphene-like structures,have received considerable attention since their first discovery.On the other hand,Graphene has been extensively used in biomedical and medicinal applications.MXene and graphene,both as promising candidates of two-dimensional materials,have shown to possess high potential in future biomedical applications due to their unique physicochemical properties such as superior electrical conductivity,high biocompatibility,large surface area,optical and magnetic features,and extraordinary thermal and mechanical properties.These special structural,functional,and biological characteristics suggest that the hybrid/composite structure of MXene and graphene would be able to meet many unmet needs in different fields;particularly in medicine and biomedical engineering,where high-performance mechanical,electrical,thermal,magnetic,and optical requirements are necessary.However,the hybridization and surface functionalization should be further explored to obtain biocompatible composites/platforms with unique physicochemical properties,high stability,and multifunctionality.In addition,toxicological and long-term biosafety assessments and clinical translation evaluations should be given high priority in research.Although very limited studies have revealed the excellent potentials of MXene/graphene in biomedicine,the next steps should be toward the extensive research and detailed analysis in optimizing the properties and improving their functionality with a clinical and industrial outlook.Herein,different synthesis/fabrication methods and performances of MXene/graphene composites are discussed for potential biomedical applications.The potential toxicological effects of these composites on human cells and tissues are also covered,and future perspectives toward more successful translational applications are presented.The current state-of-the-art biotechnological advances in the use of MXene-Graphene composites,as well as their developmental challenges and future prospects are also deliberated.Due to the superior properties and multifunctionality of MXene-graphene composites,these hybrid structures can open up considerable new horizons in future of healthcare and medicine.展开更多
As the indispensable second cellular messenger,calcium signaling is involved in the regulation of almost all physiological processes by activating specific target proteins.The importance of calcium ions(Ca^(2+))makes ...As the indispensable second cellular messenger,calcium signaling is involved in the regulation of almost all physiological processes by activating specific target proteins.The importance of calcium ions(Ca^(2+))makes its“Janus nature”strictly regulated by its concentration.Abnormal regulation of calcium signals may cause some diseases;however,artificial regulation of calcium homeostasis in local lesions may also play a therapeutic role.“Calcium overload,”for example,is characterized by excessive enrichment of intracellular Ca^(2+),which irreversibly switches calcium signaling from“positive regulation”to“reverse destruction,”leading to cell death.However,this undesirable death could be defined as“calcicoptosis”to offer a novel approach for cancer treatment.Indeed,Ca^(2+)is involved in various cancer diagnostic and therapeutic events,including calcium overload-induced calcium homeostasis disorder,calcium channels dysregulation,mitochondrial dysfunction,calcium-associated immunoregulation,cell/vascular/tumor calcification,and calcification-mediated CT imaging.In paral-lel,the development of multifunctional calcium-based nanomaterials(e.g.,calcium phosphate,calcium carbonate,calcium peroxide,and hydroxyapatite)is becoming abundantly available.This review will highlight the latest insights of the calcium-based nanomaterials,explain their application,and provide novel perspective.Identifying and characterizing new patterns of calcium-dependent signaling and exploiting the disease element linkage offer additional translational opportunities for cancer theranostics.展开更多
Dual-functional aggregation-induced photosensitizers(AIE-PSs)with singlet oxygen generation(SOG)ability and bright fluorescence in aggregated state have received much attention in image-guided photodynamic therapy(PDT...Dual-functional aggregation-induced photosensitizers(AIE-PSs)with singlet oxygen generation(SOG)ability and bright fluorescence in aggregated state have received much attention in image-guided photodynamic therapy(PDT).However,designing an AIE-PS with both high SOG and intense fluorescence via molecular design is still challenging.In this work,we report a new nanohybrid consisting of gold nanostar(AuNS)and AIE-PS dots with enhanced fluorescence and photosensitization for theranostic applications.The spectral overlap between the extinction of AuNS and fluorescence emission of AIE-PS dots(665 nm)is carefully selected using five different AuNSs with distinct localized surface plasmon(LSPR)peaks.Results show that all the AuNS s can enhance the 1 O2 production of AIE-PS dots,among which the AuNS with LSPR peak at 585 nm exhibited the highest 1 O2 enhancement factor of15-fold with increased fluorescence brightness.To the best of our knowledge,this is the highest enhancement factor reported for the metalenhanced singlet oxygen generation systems.The Au585@AIE-PS nanodots were applied for simultaneous fluorescence imaging and photodynamic ablation of HeLa cancer cells with strongly enhanced PDT efficiency in vitro.This study provides a better understanding of the metal-enhanced AIE-PS nanohybrid systems,opening up new avenue towards advanced image-guided PDT with greatly improved efficacy.展开更多
MXene-based nanozymes have garnered considerable attention because of their potential environmental and biomedical applications.These materials encompass alluring and manageable catalytic performances and physicochemi...MXene-based nanozymes have garnered considerable attention because of their potential environmental and biomedical applications.These materials encompass alluring and manageable catalytic performances and physicochemical features,which make them suitable as(bio)sensors with high selectivity/sensitivity and efficiency.MXene-based structures with suitable electrical conductivity,biocompatibility,large surface area,optical/magnetic properties,and thermal/mechanical features can be applied in designing innovative nanozymes with area-dependent electrocatalytic performances.Despite the advances made,there is still a long way to deploy MXene-based nanozymes,especially in medical and healthcare applications;limitations pertaining the peroxidaselike activity and sensitivity/selectivity may restrict further practical applications of pristine MXenes.Thus,developing an efficient surface engineering tactic is still required to fabricate multifunctional MXene-based nanozymes with excellent activity.To obtain MXene-based nanozymes with unique physicochemical features and high stability,some crucial steps such as hybridization and modification ought to be performed.Notably,(nano)toxicological and long-term biosafety analyses along with clinical translation studies still need to be comprehensively addressed.Although very limited reports exist pertaining to the biomedical potentials of MXene-based nanozymes,the future explorations should transition toward the extensive research and detailed analyses to realize additional potentials of these structures in biomedicine with a focus on clinical and industrial aspects.In this perspective,therapeutic,diagnostic,and theranostic applications of MXene-based nanozymes are deliberated with a focus on future per-spectives toward more successful clinical translational studies.The current state-of-the-art biomedical advances in the use of MXene-based nanozymes,as well as their developmental challenges and future prospects are also highlighted.In view of the fascinating properties of MXene-based nanozymes,these materials can open significant new opportunities in the future of bio-and nanomedicine.展开更多
ABSTRACT Lung cancer is a complex thoracic malignancy developing consequential to aberrations in a myriad of molecular and biomolecular signaling pathways.It is one of the most lethal forms of cancers accounting to al...ABSTRACT Lung cancer is a complex thoracic malignancy developing consequential to aberrations in a myriad of molecular and biomolecular signaling pathways.It is one of the most lethal forms of cancers accounting to almost 1.8 million new annual incidences,bearing overall mortality to incidence ratio of 0.87.The dismal prognostic scenario at advanced stages of the disease and metastatic/resistant tumor cell populations stresses the requisite of advanced translational interdisciplinary interventions such as bionanotechnology.This review article deliberates insights and apprehensions on the recent prologue of nanobioengineering and bionanotechnology as an approach for the clinical management of lung cancer.The role of nanobioengineered(bio-nano)tools like bio-nanocarriers and nanobiodevices in secondary prophylaxis,diagnosis,therapeutics,and theranostics for lung cancer management has been discussed.Bioengineered,bioinspired,and biomimetic bio-nanotools of considerate translational value have been reviewed.Perspectives on existent oncostrategies,their critical comparison with bio-nanocarriers,and issues hampering their clinical bench side to bed transformation have also been summarized.展开更多
In this study, a fucoidan-based theranostic nanogel(CFN-gel) consisting of a fucoidan backbone, redox-responsive cleavable linker and photosensitizer is developed to achieve acti-vatable near-infrared fluorescence ima...In this study, a fucoidan-based theranostic nanogel(CFN-gel) consisting of a fucoidan backbone, redox-responsive cleavable linker and photosensitizer is developed to achieve acti-vatable near-infrared fluorescence imaging of tumor sites and an enhanced photodynamic therapy(PDT) to induce the com-plete death of cancer cells. A CFN-gel has nanomolar a nity for P-selectin, which is overexpressed on the surface of tumor neovascular endothelial cells as well as many other cancer cells. Therefore, a CFN-gel can enhance tumor accumulation through P-selectin targeting and the enhanced permeation and retention e ect. Moreover, a CFN-gel is non-fluorescent and non-phototoxic upon its systemic administration due to the aggregation-induced self-quenching in its fluorescence and singlet oxygen generation. After internalization into cancer cells and tumor neovascular endothelial cells, its photoactivity is recovered in response to the intracellular redox potential, thereby enabling selective near-infrared fluorescence imaging and an enhanced PDT of tumors. Since a CFN-gel also shows nanomolar a nity for the vascular endothelial growth factor, it also provides a significant anti-tumor e ect in the absence of light treatment in vivo. Our study indicates that a fucoidan-based theranostic nanogel is a new theranostic material for imaging and treating cancer with high e cacy and specificity.展开更多
基金supported by the National Key Research and Development Program of China(2017YFA0205201 and 2016YFC0106900)the National Natural Science Foundation of China(81925019,81422023,81701752,81901808,and U1705281)+2 种基金the Fundamental Research Funds for the Central Universities(20720200019 and 20720190088)the Program for New Century Excellent Talents in University,China(No.NCET-13-0502)the China Postdoctoral Science Foundation(2019M662545)。
文摘Rapid evolution and propagation of multidrug resistance among bacterial pathogens are outpacing the development of new antibiotics,but antimicrobial photodynamic therapy(aPDT)provides an excellent alternative.This treatment depends on the interaction between light and photoactivated sensitizer to generate reactive oxygen species(ROS),which are highly cytotoxic to induce apoptosis in virtually all microorganisms without resistance concern.When replacing light with low-frequency ultrasonic wave to activate sensitizer,a novel ultrasounddriven treatment emerges as antimicrobial sonodynamic therapy(aSDT).Recent advances in aPDT and aSDT reveal golden opportunities for the management of multidrug resistant bacterial infections,especially in the theranostic application where imaging diagnosis can be accomplished facilely with the inherent optical characteristics of sensitizers,and the generated ROS by aPDT/SDT cause broad-spectrum oxidative damage for sterilization.In this review,we systemically outline the mechanisms,targets,and current progress of aPDT/SDT for bacterial theranostic application.Furthermore,potential limitations and future perspectives are also highlighted.
基金the US METAvivor Early Career Investigator Award(W.T.)and Harvard Medical School/Brigham and Women’s Hospital Department of Anesthesiology-Basic Scientist Grant(W.T.)National Natural Science Foundation of China(Nos.21877049,21807117)+2 种基金Major Program for Tackling Key Problems of Industrial Technology in Guangzhou(201902020013)Dedicated Fund for Promoting High-Quality Marine Economic Development in Guangdong Province(GDOE-2019-A31,2020-035)Dr J.Ouyang was supported by the China Postdoctoral Science Foundation(No.2020M683173).
文摘Stanene(Sn)-based materials have been extensively applied in industrial production and daily life,but their potential biomedical application remains largely unexplored,which is due to the absence of the appropriate and effective methods for fabricating Sn-based biomaterials.Herein,we explored a new approach combining cryogenic exfoliation and liquid-phase exfoliation to successfully manufacture two-dimensional(2D)Sn nanosheets(SnNSs).The obtained SnNSs exhibited a typical sheet-like structure with an average size of~100 nm and a thickness of~5.1 nm.After PEGylation,the resulting PEGylated SnNSs(SnNSs@PEG)exhibited good stability,superior biocompatibility,and excellent photothermal performance,which could serve as robust photothermal agents for multi-modal imaging(fluorescence/photoacoustic/photothermal imaging)-guided photothermal elimination of cancer.Furthermore,we also used first-principles density functional theory calculations to investigate the photothermal mechanism of SnNSs,revealing that the free electrons in upper and lower layers of SnNSs contribute to the conversion of the photo to thermal.This work not only introduces a new approach to fabricate 2D SnNSs but also establishes the SnNSs-based nanomedicines for photonic cancer theranostics.This new type of SnNSs with great potential in the field of nanomedicines may spur a wave of developing Sn-based biological materials to benefit biomedical applications.
基金supported by the National Research Foundation of Korea(CRI project no.2018R1A3B1052702 and 2019M3E5D1A01068998,J.S.K.)Basic Science Research Program(2020R1A6A3A01100551,M.W.and 2020R1A6A3A01100558,S.K.)funded by the Ministry of EducationKorea University Grant。
文摘The insistent demand for space-controllable delivery,which reduces the side effects of non-steroidal antiinflammatory drugs(NSAIDs),has led to the development of a new theranostics-based approach for anti-inflammatory therapy.The current anti-inflammatory treatments can be improved by designing a drug delivery system responsive to the inflammatory site biomarker,hydrogen polysulfide(H_(2)S_(n)).Here,we report a noveltheranostic agent 1(TA1),consisting of three parts:H_(2)S_(n)-mediated triggering part,a two-photon fluorophore bearing mitochondria targeting unit(Rhodol-TPP),and anti-inflammatory COX inhibitor(indomethacin).In vitro experiments showed that TA1 selectively reacts with H_(2)S_(n)to concomitantly release both Rhodol-TPP and indomethacin.Confocal-microscopy imaging of inflammation-inducedlive cells suggested that TA1 is localized in the mitochondria where the H_(2)S_(n)is overexpressed.The TA1 reacted with H_(2)S_(n)in the endogenous and exogenous H_(2)S_(n)environments and in lipopolysaccharide treated inflammatory cells.Moreover,TA1 suppressed COX-2 level in the inflammatory-induced cells and prostaglandin E 2(PGE2)level in blood serum from inflammation-induced mouse models.In vivo experiments with inflammation-induced mouse models suggested that TA1 exhibits inflammation-site-elective drug release followed by significant therapeutic e ects,showing its function as a theranostic agent,capable of both anti-inflammatory therapy and precise diagnosis.Theranostic behavior of TA1 is highly applicable in vivo model therapeutics for the inflammatory disease.
基金Project partially supported by the School of Pharmacy,University College London
文摘Many studies have recently attempted to develop multifunctional nanoconstructs by integrating the superior fluores- cence properties of quantum dots （QD） with therapeutic capabilities into a single vesicle for cancer theranostics. Liposome- quantum dot （L-QD） hybrid vesicles have shown promising potential for the construction of multifunctional nanoconstructs for cancer imaging and therapy. To fulfil such a potential, we report here the further functionalization of L-QD hybrid vesi- cles with therapeutic capabilities by loading anticancer drug doxorubicin （Dox） into their aqueous core. L-QD hybrid vesi- cles are first engineered by the incorporation of TOPO-capped, CdSe/ZnS QD into the lipid bilayers of DSPC：Chol：DSPE- PEG2000, followed by Dox loading using the pH-gradient technique. The loading efficiency of Dox into L-QD hybrid vesicles is achieved up to 97%, comparable to liposome control. All these evidences prove that the incorporation of QD into the lipid bilayer does not affect Dox loading through the lipid membrane of liposomes using the pH-gradient technique. Moreover, the release study shows that Dox release profile can be modulated simply by changing lipid composition. In conclusion, the Dox-loaded L-QD hybrid vesicles presented here constitute a promising multifunctional nanoconstruct capable of transporting combinations of therapeutic and diagnostic modalities.
基金S.G.acknowledges the financial support from the National Natural Science Foundation of China(NSFC 52272144,51972076)the Heilongjiang Provincial Natural Science Foundation of China(JQ2022E001)+4 种基金the Natural Science Foundation of Shandong Province(ZR2020ZD42)the Fundamental Research Funds for the Central Universities.H.D.acknowledges the financial support from the National Natural Science Foundation of China(NSFC 22205048)China Postdoctoral Science Foundation(2022M710931 and 2023T160154)Heilongjiang Postdoctoral Science Foundation(LBH-Z22010)G.Y.acknowledges the financial support from the National Science Foundation of Heilongjiang Education Department(324022075).
文摘Since the discovery of enzyme-like activity of Fe3O4 nanoparticles in 2007,nanozymes are becoming the promising substitutes for natural enzymes due to their advantages of high catalytic activity,low cost,mild reaction conditions,good stability,and suitable for large-scale production.Recently,with the cross fusion of nanomedicine and nanocatalysis,nanozyme-based theranostic strategies attract great attention,since the enzymatic reactions can be triggered in the tumor microenvironment to achieve good curative effect with substrate specificity and low side effects.Thus,various nanozymes have been developed and used for tumor therapy.In this review,more than 270 research articles are discussed systematically to present progress in the past five years.First,the discovery and development of nanozymes are summarized.Second,classification and catalytic mechanism of nanozymes are discussed.Third,activity prediction and rational design of nanozymes are focused by highlighting the methods of density functional theory,machine learning,biomimetic and chemical design.Then,synergistic theranostic strategy of nanozymes are introduced.Finally,current challenges and future prospects of nanozymes used for tumor theranostic are outlined,including selectivity,biosafety,repeatability and stability,in-depth catalytic mechanism,predicting and evaluating activities.
基金support for this research from the National Natural Science Foundation of China (Grant No. 81071249, 81171446 and 20905050)Guangdong Innovation Team of Low-cost Healthcare, Science and Technology Key Project of Guangdong (2009A030301010) and Shenzhen (CXB201005250029A, JC201005270326A, JC201005260247A, JC201104220242A)
文摘Theranostics is a concept that integrated imaging and therapy. As an emerging field, it embraces multiple techniques to arrive at an individualized treatment purpose. Indocyanine green(ICG) is a near infrared dye that has been approved by Food and Drug Administration(FDA) in USA for the use in indicator-dilution studies in humans. ICG nanoparticles(NPs) have attracted much attention for its potential applications in cancer theranostics. This review focuses on the preparation, application of ICG NPs for in vivo imaging(fluorescent imaging and photoacoustic imaging) and therapeutics(photothermal therapy, photodynamic therapy and photoacoustic therapy), and future directions based on recent developments in these areas. It is hoped that this review might provide new impetus to understand ICG NPs for cancer theranostics.
基金This work is supported by the Singapore Agency for Science,Technology and Research(A*STAR)AME IRG Grant No.(A20E5c0081)the Singapore Academic Research Fund(RG3/21)+1 种基金and the Singapore National Research Foundation Investigatorship(NRF-NRFI2018-03)Open access funding provided by Shanghai Jiao Tong University
文摘Natural enzymes usually suffer from high production cost,ease of denaturation and inactivation,and low yield,making them difficult to be broadly applicable.As an emerging type of artificial enzyme,nanozymes that combine the characteristics of nanomaterials and enzymes are promising alternatives.On the one hand,nanozymes have high enzyme-like catalytic activities to regulate biochemical reactions.On the other hand,nanozymes also inherit the properties of nanomaterials,which can ameliorate the shortcomings of natural enzymes and serve as versatile platforms for diverse applications.In this review,various nanozymes that mimic the catalytic activity of different enzymes are introduced.The achievements of nanozymes in different cancer diagnosis and treatment technologies are summarized by highlighting the advantages of nanozymes in these applications.Finally,future research directions in this rapidly developing field are outlooked.
基金support from the National Institute of Biomedical Imaging and Bioengineering (5T32EB009035)
文摘MXenes,transition metal carbides and nitrides with graphene-like structures,have received considerable attention since their first discovery.On the other hand,Graphene has been extensively used in biomedical and medicinal applications.MXene and graphene,both as promising candidates of two-dimensional materials,have shown to possess high potential in future biomedical applications due to their unique physicochemical properties such as superior electrical conductivity,high biocompatibility,large surface area,optical and magnetic features,and extraordinary thermal and mechanical properties.These special structural,functional,and biological characteristics suggest that the hybrid/composite structure of MXene and graphene would be able to meet many unmet needs in different fields;particularly in medicine and biomedical engineering,where high-performance mechanical,electrical,thermal,magnetic,and optical requirements are necessary.However,the hybridization and surface functionalization should be further explored to obtain biocompatible composites/platforms with unique physicochemical properties,high stability,and multifunctionality.In addition,toxicological and long-term biosafety assessments and clinical translation evaluations should be given high priority in research.Although very limited studies have revealed the excellent potentials of MXene/graphene in biomedicine,the next steps should be toward the extensive research and detailed analysis in optimizing the properties and improving their functionality with a clinical and industrial outlook.Herein,different synthesis/fabrication methods and performances of MXene/graphene composites are discussed for potential biomedical applications.The potential toxicological effects of these composites on human cells and tissues are also covered,and future perspectives toward more successful translational applications are presented.The current state-of-the-art biotechnological advances in the use of MXene-Graphene composites,as well as their developmental challenges and future prospects are also deliberated.Due to the superior properties and multifunctionality of MXene-graphene composites,these hybrid structures can open up considerable new horizons in future of healthcare and medicine.
基金supported by the Major State Basic Research Development Program of China(No.2017YFA0205201)China Postdoctoral Science Foundation Funded Project(2021M702743)the National Natural Science Foundation of China(NSFC,Nos.81925019,32101113,and U1705281).
文摘As the indispensable second cellular messenger,calcium signaling is involved in the regulation of almost all physiological processes by activating specific target proteins.The importance of calcium ions(Ca^(2+))makes its“Janus nature”strictly regulated by its concentration.Abnormal regulation of calcium signals may cause some diseases;however,artificial regulation of calcium homeostasis in local lesions may also play a therapeutic role.“Calcium overload,”for example,is characterized by excessive enrichment of intracellular Ca^(2+),which irreversibly switches calcium signaling from“positive regulation”to“reverse destruction,”leading to cell death.However,this undesirable death could be defined as“calcicoptosis”to offer a novel approach for cancer treatment.Indeed,Ca^(2+)is involved in various cancer diagnostic and therapeutic events,including calcium overload-induced calcium homeostasis disorder,calcium channels dysregulation,mitochondrial dysfunction,calcium-associated immunoregulation,cell/vascular/tumor calcification,and calcification-mediated CT imaging.In paral-lel,the development of multifunctional calcium-based nanomaterials(e.g.,calcium phosphate,calcium carbonate,calcium peroxide,and hydroxyapatite)is becoming abundantly available.This review will highlight the latest insights of the calcium-based nanomaterials,explain their application,and provide novel perspective.Identifying and characterizing new patterns of calcium-dependent signaling and exploiting the disease element linkage offer additional translational opportunities for cancer theranostics.
基金supported by the Institute of Materials Research and Engineering under Biomimetic and Biomedical Materials program(IMRE/00-1P1400)Newcastle University(RSA/CCEAMD5010)+1 种基金National University of Singapore(R279-000-482-133)The funding from NRF Investigatorship(R279-000-444-281)is also appreciated。
文摘Dual-functional aggregation-induced photosensitizers(AIE-PSs)with singlet oxygen generation(SOG)ability and bright fluorescence in aggregated state have received much attention in image-guided photodynamic therapy(PDT).However,designing an AIE-PS with both high SOG and intense fluorescence via molecular design is still challenging.In this work,we report a new nanohybrid consisting of gold nanostar(AuNS)and AIE-PS dots with enhanced fluorescence and photosensitization for theranostic applications.The spectral overlap between the extinction of AuNS and fluorescence emission of AIE-PS dots(665 nm)is carefully selected using five different AuNSs with distinct localized surface plasmon(LSPR)peaks.Results show that all the AuNS s can enhance the 1 O2 production of AIE-PS dots,among which the AuNS with LSPR peak at 585 nm exhibited the highest 1 O2 enhancement factor of15-fold with increased fluorescence brightness.To the best of our knowledge,this is the highest enhancement factor reported for the metalenhanced singlet oxygen generation systems.The Au585@AIE-PS nanodots were applied for simultaneous fluorescence imaging and photodynamic ablation of HeLa cancer cells with strongly enhanced PDT efficiency in vitro.This study provides a better understanding of the metal-enhanced AIE-PS nanohybrid systems,opening up new avenue towards advanced image-guided PDT with greatly improved efficacy.
文摘MXene-based nanozymes have garnered considerable attention because of their potential environmental and biomedical applications.These materials encompass alluring and manageable catalytic performances and physicochemical features,which make them suitable as(bio)sensors with high selectivity/sensitivity and efficiency.MXene-based structures with suitable electrical conductivity,biocompatibility,large surface area,optical/magnetic properties,and thermal/mechanical features can be applied in designing innovative nanozymes with area-dependent electrocatalytic performances.Despite the advances made,there is still a long way to deploy MXene-based nanozymes,especially in medical and healthcare applications;limitations pertaining the peroxidaselike activity and sensitivity/selectivity may restrict further practical applications of pristine MXenes.Thus,developing an efficient surface engineering tactic is still required to fabricate multifunctional MXene-based nanozymes with excellent activity.To obtain MXene-based nanozymes with unique physicochemical features and high stability,some crucial steps such as hybridization and modification ought to be performed.Notably,(nano)toxicological and long-term biosafety analyses along with clinical translation studies still need to be comprehensively addressed.Although very limited reports exist pertaining to the biomedical potentials of MXene-based nanozymes,the future explorations should transition toward the extensive research and detailed analyses to realize additional potentials of these structures in biomedicine with a focus on clinical and industrial aspects.In this perspective,therapeutic,diagnostic,and theranostic applications of MXene-based nanozymes are deliberated with a focus on future per-spectives toward more successful clinical translational studies.The current state-of-the-art biomedical advances in the use of MXene-based nanozymes,as well as their developmental challenges and future prospects are also highlighted.In view of the fascinating properties of MXene-based nanozymes,these materials can open significant new opportunities in the future of bio-and nanomedicine.
基金The authors are grateful to Nirma University,Ahmedabad,India,for providing financial assistance in form of a Major Research Project(NU/Ph.D./Major Res Pro/IP/16-17/669)for providing the necessary facilities to carry out the research work.The authors are also thankful to the Department of Science and Technology(DST),Fund for Improvement of S&T Infrastructure(FIST)(Grant No.:SR/FST/LSI-607/2014),Government of India for providing the necessary funding to establish equipment facility.Ms.Shruti Rawal is also grateful to Nirma University for providing the Junior Research Fellowship and Senior Research Fellowship.
文摘ABSTRACT Lung cancer is a complex thoracic malignancy developing consequential to aberrations in a myriad of molecular and biomolecular signaling pathways.It is one of the most lethal forms of cancers accounting to almost 1.8 million new annual incidences,bearing overall mortality to incidence ratio of 0.87.The dismal prognostic scenario at advanced stages of the disease and metastatic/resistant tumor cell populations stresses the requisite of advanced translational interdisciplinary interventions such as bionanotechnology.This review article deliberates insights and apprehensions on the recent prologue of nanobioengineering and bionanotechnology as an approach for the clinical management of lung cancer.The role of nanobioengineered(bio-nano)tools like bio-nanocarriers and nanobiodevices in secondary prophylaxis,diagnosis,therapeutics,and theranostics for lung cancer management has been discussed.Bioengineered,bioinspired,and biomimetic bio-nanotools of considerate translational value have been reviewed.Perspectives on existent oncostrategies,their critical comparison with bio-nanocarriers,and issues hampering their clinical bench side to bed transformation have also been summarized.
基金supported by the Ministry of Oceans and Fisheries,Korea(the project title:Development of marine material based near infrared fluorophore complex and diagnostic imaging instruments)by a Grant(1910070)from the National Cancer Center
文摘In this study, a fucoidan-based theranostic nanogel(CFN-gel) consisting of a fucoidan backbone, redox-responsive cleavable linker and photosensitizer is developed to achieve acti-vatable near-infrared fluorescence imaging of tumor sites and an enhanced photodynamic therapy(PDT) to induce the com-plete death of cancer cells. A CFN-gel has nanomolar a nity for P-selectin, which is overexpressed on the surface of tumor neovascular endothelial cells as well as many other cancer cells. Therefore, a CFN-gel can enhance tumor accumulation through P-selectin targeting and the enhanced permeation and retention e ect. Moreover, a CFN-gel is non-fluorescent and non-phototoxic upon its systemic administration due to the aggregation-induced self-quenching in its fluorescence and singlet oxygen generation. After internalization into cancer cells and tumor neovascular endothelial cells, its photoactivity is recovered in response to the intracellular redox potential, thereby enabling selective near-infrared fluorescence imaging and an enhanced PDT of tumors. Since a CFN-gel also shows nanomolar a nity for the vascular endothelial growth factor, it also provides a significant anti-tumor e ect in the absence of light treatment in vivo. Our study indicates that a fucoidan-based theranostic nanogel is a new theranostic material for imaging and treating cancer with high e cacy and specificity.
