To effectively penetrate the blood-brain barrier(BBB)and integrate magnetic resonance imaging(MRI)diagnosis and multitarget therapy for orthotopic glioma,we proposed to develop a multinuclear gadolinium(Gd)complex bas...To effectively penetrate the blood-brain barrier(BBB)and integrate magnetic resonance imaging(MRI)diagnosis and multitarget therapy for orthotopic glioma,we proposed to develop a multinuclear gadolinium(Gd)complex based on apoferritin(AFt).To this end,we rationally designed and synthesized a trinuclear Gd(Ⅲ)complex(Gd3)with strong T_(1)-weighted MRI performance and remarkable cytotoxicity against glioma cells in vitro.Subsequently,we constructed an AFt-Gd3 nanoparticle(NP)delivery system.AFt-Gd3 NPs not only penetrate BBB but also provide significant T_(1)-weighted MRI contrast for orthotopic glioma while effectively inhibiting glioma growth with minimal side effects in vivo.Furthermore,we elucidate the mechanism by which AFt-Gd3 NPs inhibit glioma growth:inducing apoptosis through chemodynamic therapy,blocking glutamine metabolism,and inhibiting energy metabolism.展开更多
For precise personalized treatment of triple-negative breast cancer(TNBC)and inhibition of its metastasis,we innovatively designed and synthesized a gadolinium(Ⅲ)-copper(Ⅰ)complex(GdCu)with remarkable performance in...For precise personalized treatment of triple-negative breast cancer(TNBC)and inhibition of its metastasis,we innovatively designed and synthesized a gadolinium(Ⅲ)-copper(Ⅰ)complex(GdCu)with remarkable performance in T1-weighted magnetic resonance imaging(MRI)and cytotoxicity to TNBC cells.In addition,we constructed a GdCu@apoferritin(AFt)nanoparticles(NPs)delivery system.GdCu and GdCu@AFt NPs significantly inhibited the migration and invasion of MDA-MB-231 cells in vitro.GdCu can significantly inhibit the growth and metastasis of TNBC in vivo.GdCu@AFt NPs not only improved the targeting ability of GdCu,showed an enhanced performance of MRI and tumor-growth inhibition,but also decreased the systemic toxicity of GdCu in vivo.We demonstrated that GdCu and GdCu@AFt NPs prevented the growth and metastasis of TNBC by inducing mitochondria-mediated apoptosis and inhibiting cancer cell stemness.The remarkable MRI,anticancer and anti-metastasis capabilities of GdCu and GdCu@AFt NPs make them promising agents for the targeted theranostics of TNBC.展开更多
Proteolysis-targeting chimera(PROTAC)has emerged as an efficient strategy to accurately control intracellular protein levels.However,conventional PROTACs are generally limited by nonspecific protein degradation and of...Proteolysis-targeting chimera(PROTAC)has emerged as an efficient strategy to accurately control intracellular protein levels.However,conventional PROTACs are generally limited by nonspecific protein degradation and off-tissue side effects.Particularly,there is a lack of effective chemical tools for visualizing protein degradation.Herein,a near-infrared fluorescent and theranostic PROTAC(PRO-S-DCM)was designed for imaging the degradation of bromodomain-containing protein 4(BRD4).PRO-S-DCM could be tumor-specifically activated and exhibited favorable imaging effects both in vitro and in vivo.PRO-S-DCM was proven to be a theranostic probe,which potently inhibited growth,invasion and migration of He La cells and induced cell apoptosis.展开更多
Photodynamic therapy(PDT)is widely used in cancer treatment because of its noninvasiveness and minimal side effects.However,low therapeutic efficiency and the challenge of treatment visualization limit its development...Photodynamic therapy(PDT)is widely used in cancer treatment because of its noninvasiveness and minimal side effects.However,low therapeutic efficiency and the challenge of treatment visualization limit its development.Herein,we constructed a simple yet efficient lanthanide-doped theranostic nanoplatform termed as LiLuF_(4):Yb,Er,Ce@LiYF_(4)@LiLuF_(4):Nd-chlorine 6(TNPs-Ce6)that enables real-time monitoring of the therapeutic effects of PDT.Upon orthogonal excitation by near-infrared(NIR)light,the Nd^(3+)-doped TNPs activated the triplets of Ce6 photosensitizers via a direct lanthanide-triplet energy transfer process,which allowed to directly active the low-lying triplet state of the photosensitizer without undergoing singlet-triplet intersystem crossing(ISC)process,thereby significantly enhancing the efficiency of the photodynamic process.Meanwhile,the incorporation of Er^(3+)ions within the core endowed the nanoplatform with NIR-Ⅱb imaging capabilities,allowing convenient real-time monitoring of the photodynamic treatment process.Characterization tests revealed that the TNPs-Ce6 nanoplatform,exhibiting an NIR quantum yield of 21.7%at an ultralow excitation power density of 0.1 W cm^(-2),provides a real-time imaging resolution as low as75μm in the NIR-Ⅱb range and achieves a tumor suppression rate of 94%.Therefore,this highly efficient theranostic nanoplatform,with real-time treatment monitoring capability,demonstrates significant potential in cancer therapy.展开更多
1|Introduction Theranostics is quickly establishing itself as a key component in the field of cancer diagnosis and treatment^([1]).It is now considered the fifth pillar of contemporary oncology manage-ment alongside s...1|Introduction Theranostics is quickly establishing itself as a key component in the field of cancer diagnosis and treatment^([1]).It is now considered the fifth pillar of contemporary oncology manage-ment alongside surgery,chemotherapy,radiotherapy,and immunotherapy^([2]).As theranostics continues to evolve,it is essential for clinicians and radiologists to be aware of the cur-rent landscape and trends in the field^([3-5]).This article aims to highlight the importance for global radiology training colleges to formally introduce theranostics into their training curricula.This is to ensure that their trainees will gain adequate exposure to this growing branch of precision medicine and to enable them to contribute effectively to the field of oncology.展开更多
Up to now,numerous emerging methods of cancer treatment including chemodynamic therapy,photothermal therapy,photodynamic therapy,sonodynamic therapy,immunotherapy and chemotherapy have rapidly entered a new stage of d...Up to now,numerous emerging methods of cancer treatment including chemodynamic therapy,photothermal therapy,photodynamic therapy,sonodynamic therapy,immunotherapy and chemotherapy have rapidly entered a new stage of development.However,the single treatment mode is often constrained by the complex tumor microenvironment.Recently,the nanomaterials and nanomedicine have emerged as promising avenues to overcome the limitation in cancer theranostics.Especially,metal-organic frameworks(MOFs)have gained considerable interests in cancer therapy because of their customizable morphologies,easy functionalization,large specific surface area,and good biocompatibility.Among these MOFs,iron-based MOFs(Fe-MOFs)are particularly promising for cancer treatment due to their properties as nano-photosensitizers,peroxidase-like activity,bioimaging contrast capabilities,and biodegradability.Utilizing their structural regularity and synthetic tunability,Fe-MOFs can be engineered to incorporate organic molecules or other inorganic nanoparticles,thereby creating multifunctional nanoplatforms for single or combined theranostic modes.Herein,the minireview focuses on the recent advancements of the Fe-MOFs-based nanoplatforms for self-enhanced imaging and treatment at tumor sites.Furthermore,the clinical research development of Fe-MOFs-based nanoplatforms is discussed,addressing key challenges and innovations for the future.Our review aims to provide novice researchers with a foundational understanding of advanced cancer theranostic modes and promote their clinical applications through the modification of Fe-MOFs.展开更多
Mesoporous silica nanoparticles(MsNs)are thought to be an attractive drug delivery material because of their advantages including high specific surface area,tunable pore size and morphology,easy sur-face modification ...Mesoporous silica nanoparticles(MsNs)are thought to be an attractive drug delivery material because of their advantages including high specific surface area,tunable pore size and morphology,easy sur-face modification and good biocompatibility.However,as a result of the poor biodegradability of MsNs,their biomedical applications are limited.To break the bottleneck of limited biomedical applications of MSNs,more and more researchers tend to design biodegradable MSNs(b-MSNs)nanosystems to obtain biodegradable as well as safe and reliable drug delivery carriers.In this review,we focused on sum-marizing strategies to improve the degradability of MsNs and innovatively proposed a series of advan-tages of b-MsNs,including controlled cargo release behavior,multifunctional frameworks,nano-catalysis,bio-imaging capabilities and enhanced therapeutic effects.Based on these advantages,we have inno-vatively summarized the applications of b-MsNs for enhanced tumor theranostics,including enhanced chemotherapy,delivery of nanosensitizers,gas molecules and biomacromolecules,initiation of immune response,synergistic therapies and image-guided tumor diagnostics.Finally,the challenges and further clinical translation potential of nanosystems based on b-MsNs are fully discussed and prospected.We believe that such b-MsNs delivery carriers will provide a timely reference for further applications in tu-mor theranostics.展开更多
Thymoquinone(TQ)and gallic acid(GA)are known for counter-tumorigenic characteristics.GA inhibits cancer cell proliferation by interfering with many apoptotic signaling pathways,producing more reactive oxygen species(R...Thymoquinone(TQ)and gallic acid(GA)are known for counter-tumorigenic characteristics.GA inhibits cancer cell proliferation by interfering with many apoptotic signaling pathways,producing more reactive oxygen species(ROS),focusing on the cell cycle,and suppressing the expression of oncogenes and matrix metalloproteinases(MMPs).In this study,TQ(after reducing to thymohydroquinone)and GA are esterified to form thymohydroquinyl gallate(a prodrug).Thymohydroquinyl gallate(THQG)possesses enhanced antineoplastic efficacy and targeted delivery potential.The chemical and spectroscopic analysis confirms ester synthesis.Gold nanoparticles(AuNPs)are employed as nanocarriers due to their physicochemical and optical characteristics,biocompatibility,and low toxicity.As an efficient drug transporter,(AuNPs) shield conjugated drugs from enzymatic digestion.The prodrug acts as a reducing agent for Au metal atoms and is loaded onto it after reduction.The nano drug is radiolabeled with 99mTc and 131I to monitor the drug biodistribution in animals using a gamma camera and single-photon emission computerized tomography(SPECT).131I is an antineoplastic that helps enhance the drug's efficiency.Chromatographic results reveal promising radiolabeling percentages.In vitro,drug release shows sustained release at pH~5.8.In vitro 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide(MTT)cytotoxicity assay reveals drug potency on CAL 27 and MCF 7 cell lines.展开更多
Persistent luminescence is a unique optical phenomenon that continues to emit light for minutes or even hours after the excitation stops,which can significantly enhance the sensitivity and signal-to-noise ratio of ima...Persistent luminescence is a unique optical phenomenon that continues to emit light for minutes or even hours after the excitation stops,which can significantly enhance the sensitivity and signal-to-noise ratio of imaging[1].Among numerous persistent luminescence materials,lanthanide-doped fluoride nanoparticles have shown tunable persistent luminescence across the UV-vis-NIR spectrum(200-1700 nm)under X-ray excitation and adjustable size,promising significant applications in deep-tissue imaging[2,3],security encryption,and data storage[4].In particular,those exhibiting NIR-II luminescence(1000-1700 nm)provide key advantages such as deeper tissue penetration,higher contrast,and minimal interference from biological autofluorescence.However,challenges such as low brightness and rapid signal decay,especially in the NIR-II region,limit their effectiveness in long-term monitoring,including tumor theranostics[5].Traditional approaches like size control and surface passivation yield only marginal improvements,underscoring the need for next-generation nanoparticles with superior NIR-II brightness.展开更多
Theranostics are one of the practical aspects of personalized medicine.This concept was designed to describe a material combining diagnosis,treatment and follow up of a disease.It evolved and included molecular target...Theranostics are one of the practical aspects of personalized medicine.This concept was designed to describe a material combining diagnosis,treatment and follow up of a disease.It evolved and included molecular targeting and nanotechnologies that incorporate both diagnosis and therapeutics.In this editorial,we are presenting briefly the concept and evolution of theranostics,highlighting many applications of theranostics in daily practice and discussing future perspectives and aspects of this model in gastrointestincal cancers.展开更多
Theranostic carbon dots(CDs)have attracted widespread attention recently due to their tunable optical properties and diverse bioactivities.Beyond fluorescent imaging application,the photothermal property endows CDs wi...Theranostic carbon dots(CDs)have attracted widespread attention recently due to their tunable optical properties and diverse bioactivities.Beyond fluorescent imaging application,the photothermal property endows CDs with the potential for microbial inactivation.However,realization of the effective conversion between fluorescence and heat in one CD system has rarely been reported.Herein,we provide a simple strategy for targeted microbial theranostics based on 4-carboxyphenylboronic acid-derived CDs(PCBA-CDs)which possess concentration-dependent photoluminescence/photothermal features.At lower concentrations,PCBA-CDs show bright and stable fluorescent signals ranging from blue to green.The fluorescence intensity gradually decreases with increasing concentration,while on the contrary,the photothermal effect of PCBA-CDs ascends progressively due to the rearrangement of electronic transitions in aggregated CDs.PCBA-CDs also demonstrate high affinity to the polysaccharide structures on the surface of microbe which allows rapid microbial fluorescence imaging as well as specific photothermal ablation of pathogens in skin wounds using PCBA-CDs at lower and higher concentrations,respectively.This study supplies a facile nanotheranostic strategy for just-in-time microbial management using bioactive CDs.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
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
In the last decade,the use of nanotheranostics as emerging diagnostic and therapeutic tools for various diseases,especially cancer,is held great attention.Up to date,several approaches have been employed in order to d...In the last decade,the use of nanotheranostics as emerging diagnostic and therapeutic tools for various diseases,especially cancer,is held great attention.Up to date,several approaches have been employed in order to develop smart nanotheranostics,which combine bioactive targeting on specific tissues as well as diagnostic properties.The nanotheranostics can deliver therapeutic agents by concomitantly monitor the therapy response in real-time.Consequently,the possibility of over-or under-dosing is decreased.Various non-invasive imaging techniques have been used to quantitatively monitor the drug delivery processes.Radiolabeling of nanomaterials is widely used as powerful diagnostic approach on nuclear medicine imaging.In fact,various radiolabeled nanomaterials have been designed and developed for imaging tumors and other lesions due to their efficient characteristics.Inorganic nanoparticles as gold,silver,silica based nanomaterials or organic nanoparticles as polymers,carbon based nanomaterials,liposomes have been reported asmultifunctional nanotheranostics.In this review,the imaging modalities according to their use in various diseases are summarized,providing special details for radiolabeling.In further,the most current nanotheranostics categorized via the used nanomaterials are also summed up.To conclude,this review can be beneficial for medical and pharmaceutical society as well as material scientists who work in the field of nanotheranostics since they can use this research as guide for producing newer and more efficient nanotheranostics.展开更多
Nanomaterials with multiple functions have become more and more popular in the domain of cancer research. MoS2 has a great potential in photothermal therapy, X-ray/CT imaging and drug delivery. In this study, a water ...Nanomaterials with multiple functions have become more and more popular in the domain of cancer research. MoS2 has a great potential in photothermal therapy, X-ray/CT imaging and drug delivery. In this study, a water soluble MoS2 nanosystem(MoS2-PEG) was synthesized and explored in drug delivery, photothermal therapy(PTT) and X-ray imaging.Doxorubicin(DOX) was loaded onto MoS2-PEG with a high drug loading efficiency(~69%)and obtained a multifunctional drug delivery system(MoS2-PEG/DOX). As the drug delivery, MoS2-PEG/DOX could efficiently cross the cell membranes, and escape from the endosome via NIR light irradiation, lead to more apoptosis in MCF-7 cells, and afford higher antitumor efficacy without obvious toxic effects to normal organs owing to its prolonged blood circulation and 11.6-fold higher DTX uptake of tumor than DOX. Besides, MoS2-PEG/DOX not only served as a drug delivery system, but also as a powerful PTT agent for thermal ablation of tumor and a strong X-ray contrast agent for tumor diagnosis. In the in vitro and in vivo studies, MoS2-PEG/DOX exhibited excellent tumor-targeting efficacy, outstanding synergistic anti-cancer effect of photothermal and chemotherapy and X-ray imaging property,demonstrating that MoS2-PEG/DOX had a great potential for simultaneous diagnosis and photothermal-chemotherapy in cancer treatment.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
Colorectal cancer(CRC)is the most common gastrointestinal tract cancer worldwide and is associated with high morbidity and mortality.The development of nanosized drug delivery systems has provided a new direction in C...Colorectal cancer(CRC)is the most common gastrointestinal tract cancer worldwide and is associated with high morbidity and mortality.The development of nanosized drug delivery systems has provided a new direction in CRC treatment.Among these systems,magnetic nanoparticle(MNP)-based multifunctional platforms provide a novel strategy for magnetic resonance imaging(MRI)-related cancer theranostics.At the beginning o f this original review,the carcinogenesis and treatment status o f CRC are summarized.Then,diversified preparation and functionalization methods of MNPs are systematically analyzed,followed by MRIinvolved theranostic strategies.The latest progress in MRI-mediated multimode diagnosis and image-guided targeted therapy in CRC management is the main focus.Finally,the major challenges in promoting MRI-induced precise theranostics of CRC in clinical practice are discussed.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
Transition metal carbide,carbonitride and nitride MXenes,as the emerging two-dimensional(2D)nanomaterials,have aroused burgeoning research interest in a broad range of applications ranging from energy conversion to bi...Transition metal carbide,carbonitride and nitride MXenes,as the emerging two-dimensional(2D)nanomaterials,have aroused burgeoning research interest in a broad range of applications ranging from energy conversion to biomedicines attributing to their distinctive planar nanostructure,physiochemical properties and biological effects.They are featured with fascinating electronic,optical,magnetic,mechanical and thermal properties,which exert significant roles in biomedical applications of 2D MXenes.In this review,we briefly summarize the recent research progress of 2D MXenes and highlight their intrinsic chemistry in theranostic nanomedicines,focusing on the synthetic chemistry for MXenes construction,surface chemistry for surface engineering,physiochemical property for theranostic application and biological chemistry for biosafety evaluation.Furthermore,based on the current achieve ments on MXenes,their potential research directio n,critical challenges and future development in biomedicine are also discussed.It is highly expected that 2D MXene-based nanosystems would have a broad application prospect in theranostic biomedicine provided the current facing critical issues and challenges are adequately solved.展开更多
Theranostics that integrates therapy and diagnosis in one system to achieve accurate cancer diagnosis and treatment has attracted tremendous interest,and has been recognized as a potential breakthrough in overcoming t...Theranostics that integrates therapy and diagnosis in one system to achieve accurate cancer diagnosis and treatment has attracted tremendous interest,and has been recognized as a potential breakthrough in overcoming the challenges of conventional oncotherapy.Nanoparticles are ideal candidates as carriers for theranostic agents,which is attributed to their extraordinary physicochemical properties,including nanoscale sizes,functional properties,prolonged blood circulation,active or passive tumor targeting,specific cellular uptake,and in some cases,excellent optical properties that ideally meet the needs of phototherapy and imaging at the same time.Overall,with the development of nanotechnology,theranostics has become a reality,and is now in the transition stage of"bench to bedside."In this review,we summarize recent progress on nanotechnology-based theranostics,i.e.,nanotheranostics,that has greatly assisted traditional therapies,and has provided therapeutic strategies emerging in recent decades,as well as"cocktail"theranostics mixing various treatment modalities.展开更多
基金supported by the Natural Science Foundation of Guangxi(2022GXNSFGA035003)Natural Science Foundation of China(82404419,22077021)the Guangxi"Bagui"Scholar Program to F.Y.
文摘To effectively penetrate the blood-brain barrier(BBB)and integrate magnetic resonance imaging(MRI)diagnosis and multitarget therapy for orthotopic glioma,we proposed to develop a multinuclear gadolinium(Gd)complex based on apoferritin(AFt).To this end,we rationally designed and synthesized a trinuclear Gd(Ⅲ)complex(Gd3)with strong T_(1)-weighted MRI performance and remarkable cytotoxicity against glioma cells in vitro.Subsequently,we constructed an AFt-Gd3 nanoparticle(NP)delivery system.AFt-Gd3 NPs not only penetrate BBB but also provide significant T_(1)-weighted MRI contrast for orthotopic glioma while effectively inhibiting glioma growth with minimal side effects in vivo.Furthermore,we elucidate the mechanism by which AFt-Gd3 NPs inhibit glioma growth:inducing apoptosis through chemodynamic therapy,blocking glutamine metabolism,and inhibiting energy metabolism.
基金supported by the Natural Science Foundation of China(No.22077021)the Natural Science Foundation of Guangxi(No.2022GXNSFGA035003).
文摘For precise personalized treatment of triple-negative breast cancer(TNBC)and inhibition of its metastasis,we innovatively designed and synthesized a gadolinium(Ⅲ)-copper(Ⅰ)complex(GdCu)with remarkable performance in T1-weighted magnetic resonance imaging(MRI)and cytotoxicity to TNBC cells.In addition,we constructed a GdCu@apoferritin(AFt)nanoparticles(NPs)delivery system.GdCu and GdCu@AFt NPs significantly inhibited the migration and invasion of MDA-MB-231 cells in vitro.GdCu can significantly inhibit the growth and metastasis of TNBC in vivo.GdCu@AFt NPs not only improved the targeting ability of GdCu,showed an enhanced performance of MRI and tumor-growth inhibition,but also decreased the systemic toxicity of GdCu in vivo.We demonstrated that GdCu and GdCu@AFt NPs prevented the growth and metastasis of TNBC by inducing mitochondria-mediated apoptosis and inhibiting cancer cell stemness.The remarkable MRI,anticancer and anti-metastasis capabilities of GdCu and GdCu@AFt NPs make them promising agents for the targeted theranostics of TNBC.
基金supported by the National Key Research and Development Program of China(No.2022YFC3401500 to C.Sheng)the National Natural Science Foundation of China(No.82030105 to C.Sheng and Nos.22077138,22377145 to S.Wu)Shanghai Rising-Star Program(No.22QA1411300 to S.Wu)。
文摘Proteolysis-targeting chimera(PROTAC)has emerged as an efficient strategy to accurately control intracellular protein levels.However,conventional PROTACs are generally limited by nonspecific protein degradation and off-tissue side effects.Particularly,there is a lack of effective chemical tools for visualizing protein degradation.Herein,a near-infrared fluorescent and theranostic PROTAC(PRO-S-DCM)was designed for imaging the degradation of bromodomain-containing protein 4(BRD4).PRO-S-DCM could be tumor-specifically activated and exhibited favorable imaging effects both in vitro and in vivo.PRO-S-DCM was proven to be a theranostic probe,which potently inhibited growth,invasion and migration of He La cells and induced cell apoptosis.
基金supported by the Major Research plan of the National Natural Science Foundation of China(No.92361202)National Natural Science Foundation of China(No.12204481)+3 种基金Fund of Fujian Science&Technology Innovation Laboratory for Optoelectronic Information(No.2020ZZ114)Natural Science Foundation of Fujian Province(Nos.2022J05102 and 2024J09062)National Key Research and Development Program of China(Nos.2022YFB3503700 and 2023YFF0713605)Self-deployment Project Research Program of Haixi Institutes,Chinese Academy of Sciences(No.CXZX-2022-GS01)
文摘Photodynamic therapy(PDT)is widely used in cancer treatment because of its noninvasiveness and minimal side effects.However,low therapeutic efficiency and the challenge of treatment visualization limit its development.Herein,we constructed a simple yet efficient lanthanide-doped theranostic nanoplatform termed as LiLuF_(4):Yb,Er,Ce@LiYF_(4)@LiLuF_(4):Nd-chlorine 6(TNPs-Ce6)that enables real-time monitoring of the therapeutic effects of PDT.Upon orthogonal excitation by near-infrared(NIR)light,the Nd^(3+)-doped TNPs activated the triplets of Ce6 photosensitizers via a direct lanthanide-triplet energy transfer process,which allowed to directly active the low-lying triplet state of the photosensitizer without undergoing singlet-triplet intersystem crossing(ISC)process,thereby significantly enhancing the efficiency of the photodynamic process.Meanwhile,the incorporation of Er^(3+)ions within the core endowed the nanoplatform with NIR-Ⅱb imaging capabilities,allowing convenient real-time monitoring of the photodynamic treatment process.Characterization tests revealed that the TNPs-Ce6 nanoplatform,exhibiting an NIR quantum yield of 21.7%at an ultralow excitation power density of 0.1 W cm^(-2),provides a real-time imaging resolution as low as75μm in the NIR-Ⅱb range and achieves a tumor suppression rate of 94%.Therefore,this highly efficient theranostic nanoplatform,with real-time treatment monitoring capability,demonstrates significant potential in cancer therapy.
文摘1|Introduction Theranostics is quickly establishing itself as a key component in the field of cancer diagnosis and treatment^([1]).It is now considered the fifth pillar of contemporary oncology manage-ment alongside surgery,chemotherapy,radiotherapy,and immunotherapy^([2]).As theranostics continues to evolve,it is essential for clinicians and radiologists to be aware of the cur-rent landscape and trends in the field^([3-5]).This article aims to highlight the importance for global radiology training colleges to formally introduce theranostics into their training curricula.This is to ensure that their trainees will gain adequate exposure to this growing branch of precision medicine and to enable them to contribute effectively to the field of oncology.
基金National Key Research and Development Program of China(No.2022YFD2200602)111 Project(No.B20088)+1 种基金National Natural Science Foundation of China(Nos.52202345 and 31930076)the Heilongjiang Touyan Innovation Team Program(Tree Genetics and Breeding Innovation Team)。
文摘Up to now,numerous emerging methods of cancer treatment including chemodynamic therapy,photothermal therapy,photodynamic therapy,sonodynamic therapy,immunotherapy and chemotherapy have rapidly entered a new stage of development.However,the single treatment mode is often constrained by the complex tumor microenvironment.Recently,the nanomaterials and nanomedicine have emerged as promising avenues to overcome the limitation in cancer theranostics.Especially,metal-organic frameworks(MOFs)have gained considerable interests in cancer therapy because of their customizable morphologies,easy functionalization,large specific surface area,and good biocompatibility.Among these MOFs,iron-based MOFs(Fe-MOFs)are particularly promising for cancer treatment due to their properties as nano-photosensitizers,peroxidase-like activity,bioimaging contrast capabilities,and biodegradability.Utilizing their structural regularity and synthetic tunability,Fe-MOFs can be engineered to incorporate organic molecules or other inorganic nanoparticles,thereby creating multifunctional nanoplatforms for single or combined theranostic modes.Herein,the minireview focuses on the recent advancements of the Fe-MOFs-based nanoplatforms for self-enhanced imaging and treatment at tumor sites.Furthermore,the clinical research development of Fe-MOFs-based nanoplatforms is discussed,addressing key challenges and innovations for the future.Our review aims to provide novice researchers with a foundational understanding of advanced cancer theranostic modes and promote their clinical applications through the modification of Fe-MOFs.
基金from"XingLiao Talent Program"of Liaoning Province(No.XLYC2203156)Shenyang Young and Middle-aged Science and Technology Innovation Talent Support Program(No.RC220397)are greatly acknowledged。
文摘Mesoporous silica nanoparticles(MsNs)are thought to be an attractive drug delivery material because of their advantages including high specific surface area,tunable pore size and morphology,easy sur-face modification and good biocompatibility.However,as a result of the poor biodegradability of MsNs,their biomedical applications are limited.To break the bottleneck of limited biomedical applications of MSNs,more and more researchers tend to design biodegradable MSNs(b-MSNs)nanosystems to obtain biodegradable as well as safe and reliable drug delivery carriers.In this review,we focused on sum-marizing strategies to improve the degradability of MsNs and innovatively proposed a series of advan-tages of b-MsNs,including controlled cargo release behavior,multifunctional frameworks,nano-catalysis,bio-imaging capabilities and enhanced therapeutic effects.Based on these advantages,we have inno-vatively summarized the applications of b-MsNs for enhanced tumor theranostics,including enhanced chemotherapy,delivery of nanosensitizers,gas molecules and biomacromolecules,initiation of immune response,synergistic therapies and image-guided tumor diagnostics.Finally,the challenges and further clinical translation potential of nanosystems based on b-MsNs are fully discussed and prospected.We believe that such b-MsNs delivery carriers will provide a timely reference for further applications in tu-mor theranostics.
文摘Thymoquinone(TQ)and gallic acid(GA)are known for counter-tumorigenic characteristics.GA inhibits cancer cell proliferation by interfering with many apoptotic signaling pathways,producing more reactive oxygen species(ROS),focusing on the cell cycle,and suppressing the expression of oncogenes and matrix metalloproteinases(MMPs).In this study,TQ(after reducing to thymohydroquinone)and GA are esterified to form thymohydroquinyl gallate(a prodrug).Thymohydroquinyl gallate(THQG)possesses enhanced antineoplastic efficacy and targeted delivery potential.The chemical and spectroscopic analysis confirms ester synthesis.Gold nanoparticles(AuNPs)are employed as nanocarriers due to their physicochemical and optical characteristics,biocompatibility,and low toxicity.As an efficient drug transporter,(AuNPs) shield conjugated drugs from enzymatic digestion.The prodrug acts as a reducing agent for Au metal atoms and is loaded onto it after reduction.The nano drug is radiolabeled with 99mTc and 131I to monitor the drug biodistribution in animals using a gamma camera and single-photon emission computerized tomography(SPECT).131I is an antineoplastic that helps enhance the drug's efficiency.Chromatographic results reveal promising radiolabeling percentages.In vitro,drug release shows sustained release at pH~5.8.In vitro 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide(MTT)cytotoxicity assay reveals drug potency on CAL 27 and MCF 7 cell lines.
基金supported by the Major Research Plan of the National Natural Science Foundation of China(No.92361202)National Natural Science Foundation of China(No.12204481).
文摘Persistent luminescence is a unique optical phenomenon that continues to emit light for minutes or even hours after the excitation stops,which can significantly enhance the sensitivity and signal-to-noise ratio of imaging[1].Among numerous persistent luminescence materials,lanthanide-doped fluoride nanoparticles have shown tunable persistent luminescence across the UV-vis-NIR spectrum(200-1700 nm)under X-ray excitation and adjustable size,promising significant applications in deep-tissue imaging[2,3],security encryption,and data storage[4].In particular,those exhibiting NIR-II luminescence(1000-1700 nm)provide key advantages such as deeper tissue penetration,higher contrast,and minimal interference from biological autofluorescence.However,challenges such as low brightness and rapid signal decay,especially in the NIR-II region,limit their effectiveness in long-term monitoring,including tumor theranostics[5].Traditional approaches like size control and surface passivation yield only marginal improvements,underscoring the need for next-generation nanoparticles with superior NIR-II brightness.
文摘Theranostics are one of the practical aspects of personalized medicine.This concept was designed to describe a material combining diagnosis,treatment and follow up of a disease.It evolved and included molecular targeting and nanotechnologies that incorporate both diagnosis and therapeutics.In this editorial,we are presenting briefly the concept and evolution of theranostics,highlighting many applications of theranostics in daily practice and discussing future perspectives and aspects of this model in gastrointestincal cancers.
基金supported by the National Natural Science Foundation of China(Nos.32071399 and 62175071)the Guangdong Basic and Applied Basic Research Foundation(Nos.2021A1515011988 and 2021A1515110265)+2 种基金the Science and Technology Program of Guangzhou(No.2019050001)the Project on the Education Department of Guangdong(Nos.2021KTSCX238 and 2022ZDZX2077)the Natural Science Research Project of Guangdong Food and Drug Vocational College(Nos.2020ZR01 and 2022ZR02).
文摘Theranostic carbon dots(CDs)have attracted widespread attention recently due to their tunable optical properties and diverse bioactivities.Beyond fluorescent imaging application,the photothermal property endows CDs with the potential for microbial inactivation.However,realization of the effective conversion between fluorescence and heat in one CD system has rarely been reported.Herein,we provide a simple strategy for targeted microbial theranostics based on 4-carboxyphenylboronic acid-derived CDs(PCBA-CDs)which possess concentration-dependent photoluminescence/photothermal features.At lower concentrations,PCBA-CDs show bright and stable fluorescent signals ranging from blue to green.The fluorescence intensity gradually decreases with increasing concentration,while on the contrary,the photothermal effect of PCBA-CDs ascends progressively due to the rearrangement of electronic transitions in aggregated CDs.PCBA-CDs also demonstrate high affinity to the polysaccharide structures on the surface of microbe which allows rapid microbial fluorescence imaging as well as specific photothermal ablation of pathogens in skin wounds using PCBA-CDs at lower and higher concentrations,respectively.This study supplies a facile nanotheranostic strategy for just-in-time microbial management using bioactive CDs.
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.
文摘In the last decade,the use of nanotheranostics as emerging diagnostic and therapeutic tools for various diseases,especially cancer,is held great attention.Up to date,several approaches have been employed in order to develop smart nanotheranostics,which combine bioactive targeting on specific tissues as well as diagnostic properties.The nanotheranostics can deliver therapeutic agents by concomitantly monitor the therapy response in real-time.Consequently,the possibility of over-or under-dosing is decreased.Various non-invasive imaging techniques have been used to quantitatively monitor the drug delivery processes.Radiolabeling of nanomaterials is widely used as powerful diagnostic approach on nuclear medicine imaging.In fact,various radiolabeled nanomaterials have been designed and developed for imaging tumors and other lesions due to their efficient characteristics.Inorganic nanoparticles as gold,silver,silica based nanomaterials or organic nanoparticles as polymers,carbon based nanomaterials,liposomes have been reported asmultifunctional nanotheranostics.In this review,the imaging modalities according to their use in various diseases are summarized,providing special details for radiolabeling.In further,the most current nanotheranostics categorized via the used nanomaterials are also summed up.To conclude,this review can be beneficial for medical and pharmaceutical society as well as material scientists who work in the field of nanotheranostics since they can use this research as guide for producing newer and more efficient nanotheranostics.
基金supported by grants from the National Natural Science Foundation of China(Nos.81273451,81302717 and81101684)
文摘Nanomaterials with multiple functions have become more and more popular in the domain of cancer research. MoS2 has a great potential in photothermal therapy, X-ray/CT imaging and drug delivery. In this study, a water soluble MoS2 nanosystem(MoS2-PEG) was synthesized and explored in drug delivery, photothermal therapy(PTT) and X-ray imaging.Doxorubicin(DOX) was loaded onto MoS2-PEG with a high drug loading efficiency(~69%)and obtained a multifunctional drug delivery system(MoS2-PEG/DOX). As the drug delivery, MoS2-PEG/DOX could efficiently cross the cell membranes, and escape from the endosome via NIR light irradiation, lead to more apoptosis in MCF-7 cells, and afford higher antitumor efficacy without obvious toxic effects to normal organs owing to its prolonged blood circulation and 11.6-fold higher DTX uptake of tumor than DOX. Besides, MoS2-PEG/DOX not only served as a drug delivery system, but also as a powerful PTT agent for thermal ablation of tumor and a strong X-ray contrast agent for tumor diagnosis. In the in vitro and in vivo studies, MoS2-PEG/DOX exhibited excellent tumor-targeting efficacy, outstanding synergistic anti-cancer effect of photothermal and chemotherapy and X-ray imaging property,demonstrating that MoS2-PEG/DOX had a great potential for simultaneous diagnosis and photothermal-chemotherapy in cancer treatment.
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.
基金the National Natural Science Foundation of China(Grant Nos.81903662,81860630,and 81560577)China Postdoctoral Science Foundation Grant(Grant No.2019M661057)+3 种基金the Applied Basic Research Programs of Shanxi Province(Grant No.201901D 211347)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(Grant No.2019L0428)the Startup Foundation for Doctors of Shanxi Province(Grant No.SD1827)the Startup Foundation for Doctors of Shanxi Medical University(Grant No.XD1824).
文摘Colorectal cancer(CRC)is the most common gastrointestinal tract cancer worldwide and is associated with high morbidity and mortality.The development of nanosized drug delivery systems has provided a new direction in CRC treatment.Among these systems,magnetic nanoparticle(MNP)-based multifunctional platforms provide a novel strategy for magnetic resonance imaging(MRI)-related cancer theranostics.At the beginning o f this original review,the carcinogenesis and treatment status o f CRC are summarized.Then,diversified preparation and functionalization methods of MNPs are systematically analyzed,followed by MRIinvolved theranostic strategies.The latest progress in MRI-mediated multimode diagnosis and image-guided targeted therapy in CRC management is the main focus.Finally,the major challenges in promoting MRI-induced precise theranostics of CRC in clinical practice are discussed.
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.
基金financially supported by the National Key R&D Program of China(No.2016YFA0203700)Postdoctoral Science Foundation of China(No.2018M630475)+2 种基金National Science Foundation for Young Scientists of China(No.51802336)National Nature Science Foundation of China(Nos.51672303,51722211)Program of Shanghai Academic Research Leader(No.18XD1404300)。
文摘Transition metal carbide,carbonitride and nitride MXenes,as the emerging two-dimensional(2D)nanomaterials,have aroused burgeoning research interest in a broad range of applications ranging from energy conversion to biomedicines attributing to their distinctive planar nanostructure,physiochemical properties and biological effects.They are featured with fascinating electronic,optical,magnetic,mechanical and thermal properties,which exert significant roles in biomedical applications of 2D MXenes.In this review,we briefly summarize the recent research progress of 2D MXenes and highlight their intrinsic chemistry in theranostic nanomedicines,focusing on the synthetic chemistry for MXenes construction,surface chemistry for surface engineering,physiochemical property for theranostic application and biological chemistry for biosafety evaluation.Furthermore,based on the current achieve ments on MXenes,their potential research directio n,critical challenges and future development in biomedicine are also discussed.It is highly expected that 2D MXene-based nanosystems would have a broad application prospect in theranostic biomedicine provided the current facing critical issues and challenges are adequately solved.
基金supported by the National Natural Science Foundation of China(Grant Nos.22077038 and 21702070)the National Basic Research Plan of China(Grant No.2018YFA0208903)+2 种基金the Postdoctoral Research Foundation of China(Grant No.2017M612461)the National Undergraduate Program for Innovation and Entrepreneurship of China(Grant No.19YA06)the Shenzhen Science and Technology Project(Grant No.JCYJ20170818161I36779)。
文摘Theranostics that integrates therapy and diagnosis in one system to achieve accurate cancer diagnosis and treatment has attracted tremendous interest,and has been recognized as a potential breakthrough in overcoming the challenges of conventional oncotherapy.Nanoparticles are ideal candidates as carriers for theranostic agents,which is attributed to their extraordinary physicochemical properties,including nanoscale sizes,functional properties,prolonged blood circulation,active or passive tumor targeting,specific cellular uptake,and in some cases,excellent optical properties that ideally meet the needs of phototherapy and imaging at the same time.Overall,with the development of nanotechnology,theranostics has become a reality,and is now in the transition stage of"bench to bedside."In this review,we summarize recent progress on nanotechnology-based theranostics,i.e.,nanotheranostics,that has greatly assisted traditional therapies,and has provided therapeutic strategies emerging in recent decades,as well as"cocktail"theranostics mixing various treatment modalities.
