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
Theranostics,integrating diagnostic and therapeutic functionalities,have emerged as advanced systems for timely cancer diagnosis and effective treatment.The development of versatile materials suitable for cancer thera...Theranostics,integrating diagnostic and therapeutic functionalities,have emerged as advanced systems for timely cancer diagnosis and effective treatment.The development of versatile materials suitable for cancer theranostics is intensifying.Porphyrin-based metal-organic frameworks(MOFs)leverage the structural diversity and designability inherent in MOFs,alongside the robust photophysical,catalytic,and biological properties of porphyrins.These materials enhance the solubility and stability of porphyrins and facilitate their stable functionalized assemblies,conferring the potential for multimodal imaging diagnostics and precision therapeutics.In this review,we summarized the potential of porphyrin-based MOFs as cancer theranostics platforms,focusing on recent advancements in porphyrin-based MOFs,and highlighting their functionalized strategies and developments in diagnostic imaging and synergistic therapies.Finally,we proposed the challenges and prospects of these emerging materials in cancer theranostics.展开更多
Individual inorganic nanoparticles （NPs） have been widely used in the fields of drug delivery, cancer imaging and therapy. There are still many hurdles that limit the performance of individual NPs for these applicat...Individual inorganic nanoparticles （NPs） have been widely used in the fields of drug delivery, cancer imaging and therapy. There are still many hurdles that limit the performance of individual NPs for these applications. The utilization of highly ordered NP ensembles opens a door to resolve these problems, as a result of their new or advanced collective properties. The assembled NPs show several advantages over individual NP-based systems, such as improved cell internalization and tumor targeting, enhanced multimodality imaging capability, superior combination therapy arising from synergistic effects, possible complete clearance from the whole body by degradation of assemblies into original small NP building blocks, and so on. In this review, we discuss the potential of utilizing assembled NP ensembles for cancer imaging and treatment by taking plasmonic vesicular assemblies of Au NPs as an example. We first summarize the recent developments in the self-assembly of plasmonic vesicular structures of NPs from amphiphilic polymer-tethered NP building blocks. We further review the utilization of plasmonic vesicles of NPs for cancer imaging （e.g. multi-photon induced luminescence, photothermal, and photoacoustic imaging）, and cancer therapy （e.g., photothermal therapy, and chemotherapy）. Finally, we outline current challenges and our perspectives along this line.展开更多
Carbon dots(CDs), as a new member of carbon nanostructures, have been widely applied in extensive fields due to their exceptional physicochemical properties. While, the emissions of most reported CDs are located in th...Carbon dots(CDs), as a new member of carbon nanostructures, have been widely applied in extensive fields due to their exceptional physicochemical properties. While, the emissions of most reported CDs are located in the blue to green range under the excitation of ultraviolet or blue light, which severely limits their practical applications, especially in photovoltaic and biological fields. Studies that focused on synthesizing CDs with long-wavelength(red to near-infrared) emission/excitation features(simply named L-w CDs) and exploring their potential applications have been frequently reported in recent years. In this review, we analyzed the key influence factors for the synthesis of CDs with long wavelength and multicolor(containing long wavelength) emissive properties, discussed possible fluorescence mechanism,and summarized their applications in sensing and cancer theranostics. Finally, the existing challenges and potential opportunities of L-w CDs are presented.展开更多
Gold nanoparticles have seen unprecedented development in the biomedical field, particularly for cancer ther- apy. They have received extensive attention because of their easy preparation, functionalization, biocompat...Gold nanoparticles have seen unprecedented development in the biomedical field, particularly for cancer ther- apy. They have received extensive attention because of their easy preparation, functionalization, biocompatibility, non-cytotoxicity, and detectability. Functionalized gold nanoparticles can be applied in the fields of drug and gene delivery, photothermal therapy, and bioimaging. This review introduces methods for preparing various shapes of gold nanoparticles and describes their current applications in the field of cancer treatment. Moreover, the review presents the development routes and current issues of gold nanoparticles in clinical theranostics.展开更多
Cyanine is a meritorious fluorogenic core for the construction of fluorescent probes and its phototherapeutic potential has been enthusiastically explored as well.Alternatively,the covalent conjugation of cyanine with...Cyanine is a meritorious fluorogenic core for the construction of fluorescent probes and its phototherapeutic potential has been enthusiastically explored as well.Alternatively,the covalent conjugation of cyanine with other potent therapeutic agents not only boosts its therapeutic efficacy but also broadens its therapeutic modality.Herein,we summarize miscellaneous cyanine-therapeutic agent conjugates in cancer theranostics from literature published between 2014 and 2020.The application scenarios of such theranostic cyanine conjugates covered common cancer therapeutic modalities,including chemotherapy,phototherapy and targeted therapy.Besides,cyanine conjugates that serve as nanocarriers for drug delivery are introduced as well.In an additional section,we analyze the potential of these conjugates for clinical translation.Overall,this review is aimed to stimulate research interest in exploring unattempted therapeutic agents and novel conjugation strategies and hopefully,accelerate clinical translation in this field.展开更多
Light-driven cancer theranostics has shown inexhaustible and vigorous vitality by virtue of its high efficacy,prominent controllability and noninvasiveness.Exploration of an all-round theranostic material simultaneous...Light-driven cancer theranostics has shown inexhaustible and vigorous vitality by virtue of its high efficacy,prominent controllability and noninvasiveness.Exploration of an all-round theranostic material simultaneously affording both multimodal diagnosis imaging and synergistic phototherapy would be an appealing yet significantly challenging task.Herein,a novel nanomedicine Ir@PPEG-MeEPO was ingeniously constructed by integrating beforehand1O2-charged amphiphilic polymer and well-tailored Ir(Ⅲ)complex IrDPTP,which was featured by second near-infrared(NIR-Ⅱ)aggregation-induced emission(AIE)tendency,efficient reactive oxygen species(ROS)generation,good photothermal conversion efficiency and high-performance hydrogen gas production.To the best of our knowledge,IrDPTP held the longest emission wavelength among all reported AIE Ir(Ⅲ)complexes.Moreover,Ir@PPEG-MeEPO was capable of controllably releasing ROS via triggered photothermal effect upon NIR irradiation,making it well-adapted to hypoxic environment of tumor.Those distinctive characteristics of Ir@PPEG-MeEPO endowed it with unprecedented performance on sextuple theranostics comprised of NIR-Ⅱfluorescence-photoacoustic-photothermal trimodal imaging and photodynamic-photothermal-hydrogen trimodal therapy,witnessed by the precise tumor diagnosis and complete tumor elimination.The study would open up new perspectives for the exploration of superior nanomedicine for practical 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
Photodynamic therapy(PDT)is a clinically representative treatment strategy for cancer.However,conventional photosensitizers(PSs)are usually hampered by poor water solubility and low targeting capacity.Here,we report t...Photodynamic therapy(PDT)is a clinically representative treatment strategy for cancer.However,conventional photosensitizers(PSs)are usually hampered by poor water solubility and low targeting capacity.Here,we report the precise molecular engineering of aptamer oligonucleotides to solubilize hydrophobic near-infrared(NIR)PSs for enhanced cancer PDT.Hydrophobic pyropheophorbide A(PA)is precisely conjugated to aptamer oligonucleotides by combing DNA solid-phase synthesis technology and Cu-free click chemistry.Precise coupling of insoluble PA to hydrophilic aptamer oligonucleotides vastly improves its solubility to as high as 750μM in water without any cosolvent,resulting in an enhanced NIR fluorescence property(quantum yield=23%)and photoactivity.Moreover,the targeting ability of aptamer oligonucleotides is not affected by our molecular engineering strategy.Abundant reactive oxygen species(ROS)are produced intracellularly with 660 nm laser irradiation,eliciting mitochondria damage and cell death.Tumor growth is effectively inhibited with a single dose of aptamer-PA conjugates without in vivo toxicity.Their therapeutic effect is more than 20-fold higher than that of PA.Compared with traditional formulation,using aptamer oligonucleotides as functional carriers to solubilize hydrophobic NIR PSs is more precise and operable.Our DNA molecular engineering strategy paves a way for the rational design of molecularly targeted medicine for future clinical cancer therapy.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
Self-assembled magnetic nanomaterials(MNMs)are a class of promising biomaterials possessing excellent physiochemical and biological characteristics,making them highly attractive in biomedical applications.A myriad of ...Self-assembled magnetic nanomaterials(MNMs)are a class of promising biomaterials possessing excellent physiochemical and biological characteristics,making them highly attractive in biomedical applications.A myriad of magnetic nanosystems can be created by using self-assembly as a synthetic tool.Favorable nano-bio interfacial properties are shown in these promising self-assembled magnetic nanosystems,while still retaining their physical/chemical functionalities.This review aims to provide a systematical overview of the self-assembled MNMs.In addition,this review highlights their implementations in cancer theranostics in detail.Overall,this review points out the direction for the application of self-assembled MNMs in biomedicine,and presents how clinical oncology could benefit from the self-assembled nanotechnology.展开更多
Photodynamic therapy(PDT)has emerged as an efficient cancer treatment method with minimal invasiveness.However,the majority of current photosensitizers(PSs)display severe dark toxicity and low tumor specificity due to...Photodynamic therapy(PDT)has emerged as an efficient cancer treatment method with minimal invasiveness.However,the majority of current photosensitizers(PSs)display severe dark toxicity and low tumor specificity due to their"always-on"photoactivity in blood circulation.To address this concern,we herein report a series of acid-activatable PSs for ultrasensitive PDT of triple-negative breast tumors.These set of novel PSs are synthesized by covalently modifying tetrakis(4-carboxyphenyl)porphyrin(TCPP)with a variety of tertiary amines for acidity-activatable fluorescence imaging and reactive oxygen species(RoS)generation.The resultant TCPP derivatives are grafted with a poly(ethylene glycol)(PEG)chain via a matrix metalloproteinase-2(MMP-2)-liable peptide spacer and chelated with Mn^(2+)for magnetic resonance imaging(MRI)capability.The PEGylated TCPP derivatives are amphiphilic and self-assemble into micellar nanoparticles to elongate blood circulation and for tumor-specific PDT.We further demonstrate that the PEGylated TCPP nanoparticles could serve as a nanoplatform to deliver the anticancer drug doxorubicin(DOX)and perform fluorescence image-guided combinatorial PDT and chemotherapy,which efficiently suppress the growth of 4T1 breast tumors and lung metastases in a mouse model.These acid-activatable PS-incorporated nanoparticles might provide a versatile platform for precise PDT and combinatorial breast cancer therapy.展开更多
The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma(HCC).Here,a fucoidan-modified mesoporous poly...The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma(HCC).Here,a fucoidan-modified mesoporous polydopamine nanoparticle dual-loaded with gadolinium iron and doxorubicin(FMPDA/Gd^(3+)/DOX)was prepared as an effective theranostic agent for magnetic resonance imaging(MRI)-guided chemo-photothermal therapy of HCC.It was found that FMPDA/Gd^(3+)/DOX had a high photothermal conversion efficiency of 33.4%and excellent T1-MRI performance with a longitudinal relaxivity(r1)value of 14.966 m M^(-1)·s^(-1).Moreover,the results suggested that FMPDA/Gd^(3+)/DOX could effectively accumulate into the tumor foci by dual-targeting the tumor-infiltrated platelets and HCC cells,which resulted from the specific interaction between fucoidan and overexpressed p-selectin receptors.The excellent tumor-homing ability and MRI-guided chemo-photothermal therapy therefore endowed FMPDA/Gd^(3+)/DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality.Overall,our study demonstrated that FMPDA/Gd^(3+)/DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics.展开更多
Nanomedicine has become an important development direction of modern medicine, and provides a new way for cancer theranostics. To extend the superior physicochemical property of nanomedicine and enhance their role in ...Nanomedicine has become an important development direction of modern medicine, and provides a new way for cancer theranostics. To extend the superior physicochemical property of nanomedicine and enhance their role in cancer theranostics,various strategies have been proposed. Among them, the introduction of oxygen vacancies can enhance the separation of electron-hole pairs and improve the nanomaterials' catalytic activity, which is beneficial for cancer diagnosis and treatment. This review briefly summarized the formation mechanism and preparation methods of various oxygen vacancy nanomaterials. Then,the effect and application of various oxygen vacancy nanomaterials, such as iron, manganese, titanium, zinc, bismuth, tungsten,cerium, and molybdenum-based nanomaterials in enhancing cancer theranostics were highlighted. At last, the prospect and challenges of oxygen vacancy nanomaterials were discussed. This review provided an overview of the relevant information on oxygen vacancy in cancer theranostics, and further promoted the development of cancer nanomedicine.展开更多
The clinical translation of nanomedicines has been strongly hampered by the limitations of delivery vehicles,promoting scientists to search for novel nanocarriers.Although cell membrane-based delivery systems have att...The clinical translation of nanomedicines has been strongly hampered by the limitations of delivery vehicles,promoting scientists to search for novel nanocarriers.Although cell membrane-based delivery systems have attracted extensive attention,further functionalizations are urgently desired to augment their theranostic functions.We propose a cell-friendly supramolecular strategy to engineer cell membranes utilizing cyclodextrin-based host–guest molecular recognitions to fix the defects arising from chemical and genetic modifcations.In this study,the supramolecular cell membrane vesicles(SCMVs)specifcally accumulate in tumors,benefting from tumor-homing capability and the enhanced permeability and retention effect.SCMVs co-delivering indocyanine green and an indoleamine 2,3-dioxygenase inhibitor effectively ablate tumors combining photodynamic therapy and immunotherapy.Driven by host–guest inclusion complexation,SCMVs successfully encapsulate resiquimod to repolarize tumor-associated macrophages into M1 phenotype,synergizing with immune checkpoint blockade therapy.This supramolecular engineering methodology based on noncovalent interactions presents a generalizable and cell-friendly tactic to develop living cell–originated nanomaterials for precise cancer therapy.展开更多
The design and development of multifunctional nano-drug delivery systems(NDDSs)is a solution that is expected to solve some intractable problems in traditional cancer treatment.In particular,metal-organic frameworks(M...The design and development of multifunctional nano-drug delivery systems(NDDSs)is a solution that is expected to solve some intractable problems in traditional cancer treatment.In particular,metal-organic frameworks(MOFs)are novel hybrid porous nanomaterials which are constructed by the coordination of metal cations or clusters and organic bridging ligands.Benefiting from their intrinsic superior properties,MOFs have captivated intensive attentions in drug release and cancer theranostic.Based on what has been achieved about MOF-based DDSs in recent years,this review introduces different stimuli-responsive mechanisms of them and their applications in cancer diagnosis and treatment systematically.Moreover,the existing challenges and future opportunities in this field are summarized.By realizing industrial production and paying attention to biosafety,their clinical applications will be enriched.展开更多
Owing to their appealing three-dimensional structures and tunable photophysical properties, emissive metallacages have been widely applied in recognition and sensing, adsorption and separation, catalysis, etc. Recentl...Owing to their appealing three-dimensional structures and tunable photophysical properties, emissive metallacages have been widely applied in recognition and sensing, adsorption and separation, catalysis, etc. Recently, the application of emissive metallacages in biomedical fields has emerged as a hot research topic, because multiple biological functionalities can be facilely integrated into metallacage-based platforms to deliver different functions. In this review, the applications of emissive metallacages in bio-imaging, delivery and cancer theranostics are systematically summarized. The dilemmas and challenges of metallacage-based biomedical materials are also raised at the end of this review. We hope this review would provide some guidance for the construction of novel emissive metallacages with biological functions, and further advance the development of emissive metallacages as biomedical materials.展开更多
The optical nanoprobes with emissions in the second near-infrared window(NIR-Ⅱ,1000-1700 nm)show low tissue autofluorescence and photon scattering;therefore,they provide high spatial resolution and acceptable tissue ...The optical nanoprobes with emissions in the second near-infrared window(NIR-Ⅱ,1000-1700 nm)show low tissue autofluorescence and photon scattering;therefore,they provide high spatial resolution and acceptable tissue penetration depth.These advantages make them appropriate for in vivo applications,including bioimaging,NIR-Ⅱtriggered disease therapy,and even on-site efficacy monitoring.Among the various developed NIR-Ⅱfluorescence probes,lanthanide-doped nanoparticles(LDNPs)exhibit high photo stability and narrow emission bandwidths with long photoluminescence lifetimes and low cytotoxicity;therefore,they have been widely studied in the biomedical field.This review summarizes the typical compositions and optical properties of recently developed NIR-Ⅱemitting LDNPs.Their applications in in vivo NIR-Ⅱbioimaging and cancer therapy are reviewed.The perspectives and challenges of NIR-ⅡLDNPs are also discussed.展开更多
The use of near-infrared （NIR） light for photodynamic therapy （PDT） is a promising strategy to circumvent the limitations of current PDT, in which visible light with limited tissue penetration depth is usually use...The use of near-infrared （NIR） light for photodynamic therapy （PDT） is a promising strategy to circumvent the limitations of current PDT, in which visible light with limited tissue penetration depth is usually used. In the present stud~ alkyl thiolated gold nanoclusters （AuNCs） were co-modified with human serum albumin （HSA） and catalase （CAT）, and then employed as a multifunctional, optical, theranostic nano-agent. In the AuNC@HSA/CAT system, the AuNCs were able to produce singlet oxygen under excitation by a 1,064-nm laser, which locates in the second NIR window （NIR-II）, and featured much lower tissue absorption and scattering, enabling NIR-II-triggered PDT. The HSA coating greatly improved the physiological stability of the nanoparticles, which showed efficient tumor retention after intravenous injection, as revealed by detecting the AuNC fluorescence. Moreover, the presence of CAT in the nanoparticles triggered decomposition of tumor endogenous H202 to generate oxygen, thereby enhancing the efficacy of PDT by relieving tumor hypoxia. Compared with conventional PDT using visible light, NIR-II-triggered PDT exhibits remarkably increased tissue penetration. Thus, we developed a new type of photosensitizing nano-agent that simultaneously enables in vivo fluorescence imaging, tumor hypoxia relief, and NIR-II light-induced in vivo PDT in the treatment of cancer.展开更多
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financially supported by Startup Foundation for Advanced Talents of Qingdao University(DC2400001387)National Natural Science Foundation of China(22074157)+3 种基金National Key R&D Program of China(2022YFA1103403)China Postdoctoral Science Foundation(2020M673541)Startup Foundation for Advanced Talents of Qingdao University(DC2100004477)State Key Laboratory of Bio-Fibers and Eco-Textiles of Qingdao University(RZ2200002491).
文摘Theranostics,integrating diagnostic and therapeutic functionalities,have emerged as advanced systems for timely cancer diagnosis and effective treatment.The development of versatile materials suitable for cancer theranostics is intensifying.Porphyrin-based metal-organic frameworks(MOFs)leverage the structural diversity and designability inherent in MOFs,alongside the robust photophysical,catalytic,and biological properties of porphyrins.These materials enhance the solubility and stability of porphyrins and facilitate their stable functionalized assemblies,conferring the potential for multimodal imaging diagnostics and precision therapeutics.In this review,we summarized the potential of porphyrin-based MOFs as cancer theranostics platforms,focusing on recent advancements in porphyrin-based MOFs,and highlighting their functionalized strategies and developments in diagnostic imaging and synergistic therapies.Finally,we proposed the challenges and prospects of these emerging materials in cancer theranostics.
文摘Individual inorganic nanoparticles （NPs） have been widely used in the fields of drug delivery, cancer imaging and therapy. There are still many hurdles that limit the performance of individual NPs for these applications. The utilization of highly ordered NP ensembles opens a door to resolve these problems, as a result of their new or advanced collective properties. The assembled NPs show several advantages over individual NP-based systems, such as improved cell internalization and tumor targeting, enhanced multimodality imaging capability, superior combination therapy arising from synergistic effects, possible complete clearance from the whole body by degradation of assemblies into original small NP building blocks, and so on. In this review, we discuss the potential of utilizing assembled NP ensembles for cancer imaging and treatment by taking plasmonic vesicular assemblies of Au NPs as an example. We first summarize the recent developments in the self-assembly of plasmonic vesicular structures of NPs from amphiphilic polymer-tethered NP building blocks. We further review the utilization of plasmonic vesicles of NPs for cancer imaging （e.g. multi-photon induced luminescence, photothermal, and photoacoustic imaging）, and cancer therapy （e.g., photothermal therapy, and chemotherapy）. Finally, we outline current challenges and our perspectives along this line.
基金the financial support from the National Natural Science Foundation of China(Nos.51902323,51872300 and U1832110)Postdoctoral Science Foundation of China(No.2020M671831)+1 种基金S&T Innovation 2025 Major Special Program of Ningbo(No.2018B10054)Zhejiang Provincial Natural Science Foundation of China(No.LY20B050003)。
文摘Carbon dots(CDs), as a new member of carbon nanostructures, have been widely applied in extensive fields due to their exceptional physicochemical properties. While, the emissions of most reported CDs are located in the blue to green range under the excitation of ultraviolet or blue light, which severely limits their practical applications, especially in photovoltaic and biological fields. Studies that focused on synthesizing CDs with long-wavelength(red to near-infrared) emission/excitation features(simply named L-w CDs) and exploring their potential applications have been frequently reported in recent years. In this review, we analyzed the key influence factors for the synthesis of CDs with long wavelength and multicolor(containing long wavelength) emissive properties, discussed possible fluorescence mechanism,and summarized their applications in sensing and cancer theranostics. Finally, the existing challenges and potential opportunities of L-w CDs are presented.
基金This work was financially supported by the National Natural Science Foundation of China （Nos. 51222307, 51233004, 51390484, 21474104 and 51473029）, the Jilin Province Science and Technology Development Program （Nos. 20120306 and 20130521011JH）, and the Open Research Fund of the Key Laboratory of Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, Youth Innovation Promotion Association, CAS.
文摘Gold nanoparticles have seen unprecedented development in the biomedical field, particularly for cancer ther- apy. They have received extensive attention because of their easy preparation, functionalization, biocompatibility, non-cytotoxicity, and detectability. Functionalized gold nanoparticles can be applied in the fields of drug and gene delivery, photothermal therapy, and bioimaging. This review introduces methods for preparing various shapes of gold nanoparticles and describes their current applications in the field of cancer treatment. Moreover, the review presents the development routes and current issues of gold nanoparticles in clinical theranostics.
基金financially supported by National Key Research and Development Program of China(No.2016YFA0201400)State Key Program of National Natural Science of China(No.81930047)+3 种基金Projects of International Cooperation and Exchanges NSFCPSF(No.31961143003)National Project for Research and Development of Major Scientific Instruments(No.81727803)Beijing Natural Science Foundation,Haidian,original innovation joint fund(No.17L20170)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(No.81421004).
文摘Cyanine is a meritorious fluorogenic core for the construction of fluorescent probes and its phototherapeutic potential has been enthusiastically explored as well.Alternatively,the covalent conjugation of cyanine with other potent therapeutic agents not only boosts its therapeutic efficacy but also broadens its therapeutic modality.Herein,we summarize miscellaneous cyanine-therapeutic agent conjugates in cancer theranostics from literature published between 2014 and 2020.The application scenarios of such theranostic cyanine conjugates covered common cancer therapeutic modalities,including chemotherapy,phototherapy and targeted therapy.Besides,cyanine conjugates that serve as nanocarriers for drug delivery are introduced as well.In an additional section,we analyze the potential of these conjugates for clinical translation.Overall,this review is aimed to stimulate research interest in exploring unattempted therapeutic agents and novel conjugation strategies and hopefully,accelerate clinical translation in this field.
基金partially supported by the National Natural Science Foundation of China(52122317,22175120,22305049)the Science and Technology Foundation of Shenzhen City(JCYJ20190808153415062,RCYX20200714114525101,20220809130438001,JSGG20220606141800001,JCYJ20200109110608167)the Pearl River Talent Recruitment Program(2019QN01Y103)。
文摘Light-driven cancer theranostics has shown inexhaustible and vigorous vitality by virtue of its high efficacy,prominent controllability and noninvasiveness.Exploration of an all-round theranostic material simultaneously affording both multimodal diagnosis imaging and synergistic phototherapy would be an appealing yet significantly challenging task.Herein,a novel nanomedicine Ir@PPEG-MeEPO was ingeniously constructed by integrating beforehand1O2-charged amphiphilic polymer and well-tailored Ir(Ⅲ)complex IrDPTP,which was featured by second near-infrared(NIR-Ⅱ)aggregation-induced emission(AIE)tendency,efficient reactive oxygen species(ROS)generation,good photothermal conversion efficiency and high-performance hydrogen gas production.To the best of our knowledge,IrDPTP held the longest emission wavelength among all reported AIE Ir(Ⅲ)complexes.Moreover,Ir@PPEG-MeEPO was capable of controllably releasing ROS via triggered photothermal effect upon NIR irradiation,making it well-adapted to hypoxic environment of tumor.Those distinctive characteristics of Ir@PPEG-MeEPO endowed it with unprecedented performance on sextuple theranostics comprised of NIR-Ⅱfluorescence-photoacoustic-photothermal trimodal imaging and photodynamic-photothermal-hydrogen trimodal therapy,witnessed by the precise tumor diagnosis and complete tumor elimination.The study would open up new perspectives for the exploration of superior nanomedicine for practical 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supported by National Key R&D Program of China(grant no.2020YFA0210800)National Natural Science Foundation of China(grant nos.52161160307 and 22205139)+3 种基金Natural Science Foundation of Shanghai(grant no.22ZR1437800)Shanghai Sailing Program(grant no.20YF1424500)Innovative Research Team of High-Level Local Universities in Shanghai,Excellent Academic Leader Programme of Shanghai Health Commission(grant no.2022XD033)Core Facility of Basic Medical Sciences in Shanghai Jiao Tong University School of Medicine.
文摘Photodynamic therapy(PDT)is a clinically representative treatment strategy for cancer.However,conventional photosensitizers(PSs)are usually hampered by poor water solubility and low targeting capacity.Here,we report the precise molecular engineering of aptamer oligonucleotides to solubilize hydrophobic near-infrared(NIR)PSs for enhanced cancer PDT.Hydrophobic pyropheophorbide A(PA)is precisely conjugated to aptamer oligonucleotides by combing DNA solid-phase synthesis technology and Cu-free click chemistry.Precise coupling of insoluble PA to hydrophilic aptamer oligonucleotides vastly improves its solubility to as high as 750μM in water without any cosolvent,resulting in an enhanced NIR fluorescence property(quantum yield=23%)and photoactivity.Moreover,the targeting ability of aptamer oligonucleotides is not affected by our molecular engineering strategy.Abundant reactive oxygen species(ROS)are produced intracellularly with 660 nm laser irradiation,eliciting mitochondria damage and cell death.Tumor growth is effectively inhibited with a single dose of aptamer-PA conjugates without in vivo toxicity.Their therapeutic effect is more than 20-fold higher than that of PA.Compared with traditional formulation,using aptamer oligonucleotides as functional carriers to solubilize hydrophobic NIR PSs is more precise and operable.Our DNA molecular engineering strategy paves a way for the rational design of molecularly targeted medicine for future clinical cancer therapy.
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Natural Science Foundation of Beijing Municipality,Grant/Award Number:L72008National Natural Science Foundation of China,Grant/Award Numbers:51672010,81421004,51631001。
文摘Self-assembled magnetic nanomaterials(MNMs)are a class of promising biomaterials possessing excellent physiochemical and biological characteristics,making them highly attractive in biomedical applications.A myriad of magnetic nanosystems can be created by using self-assembly as a synthetic tool.Favorable nano-bio interfacial properties are shown in these promising self-assembled magnetic nanosystems,while still retaining their physical/chemical functionalities.This review aims to provide a systematical overview of the self-assembled MNMs.In addition,this review highlights their implementations in cancer theranostics in detail.Overall,this review points out the direction for the application of self-assembled MNMs in biomedicine,and presents how clinical oncology could benefit from the self-assembled nanotechnology.
基金supported by the National Natural Science Foundation of China(Nos.82102915,22074043 and U22A20328)Lingang Laboratory(No.LG-QS-202206-04)+1 种基金China Postdoctoral Science Foundation(No.2021M700157)Shanghai Post-Doctoral Excellence Program(No.2021424).
文摘Photodynamic therapy(PDT)has emerged as an efficient cancer treatment method with minimal invasiveness.However,the majority of current photosensitizers(PSs)display severe dark toxicity and low tumor specificity due to their"always-on"photoactivity in blood circulation.To address this concern,we herein report a series of acid-activatable PSs for ultrasensitive PDT of triple-negative breast tumors.These set of novel PSs are synthesized by covalently modifying tetrakis(4-carboxyphenyl)porphyrin(TCPP)with a variety of tertiary amines for acidity-activatable fluorescence imaging and reactive oxygen species(RoS)generation.The resultant TCPP derivatives are grafted with a poly(ethylene glycol)(PEG)chain via a matrix metalloproteinase-2(MMP-2)-liable peptide spacer and chelated with Mn^(2+)for magnetic resonance imaging(MRI)capability.The PEGylated TCPP derivatives are amphiphilic and self-assemble into micellar nanoparticles to elongate blood circulation and for tumor-specific PDT.We further demonstrate that the PEGylated TCPP nanoparticles could serve as a nanoplatform to deliver the anticancer drug doxorubicin(DOX)and perform fluorescence image-guided combinatorial PDT and chemotherapy,which efficiently suppress the growth of 4T1 breast tumors and lung metastases in a mouse model.These acid-activatable PS-incorporated nanoparticles might provide a versatile platform for precise PDT and combinatorial breast cancer therapy.
基金supported by the National Key Research and Development projects intergovernmental cooperation in science and technology of China(2018YFE0126900)National Natural Science Foundation of China(82072025 and82072026)+2 种基金Zhejiang Provincial Natural Science Foundation(LQ21H180003)Key R&D Program of Lishui City(2021ZDYF12)Medical Health Science and Technology Project of Zhejiang Provincial Health Commission(2022RC088)。
文摘The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma(HCC).Here,a fucoidan-modified mesoporous polydopamine nanoparticle dual-loaded with gadolinium iron and doxorubicin(FMPDA/Gd^(3+)/DOX)was prepared as an effective theranostic agent for magnetic resonance imaging(MRI)-guided chemo-photothermal therapy of HCC.It was found that FMPDA/Gd^(3+)/DOX had a high photothermal conversion efficiency of 33.4%and excellent T1-MRI performance with a longitudinal relaxivity(r1)value of 14.966 m M^(-1)·s^(-1).Moreover,the results suggested that FMPDA/Gd^(3+)/DOX could effectively accumulate into the tumor foci by dual-targeting the tumor-infiltrated platelets and HCC cells,which resulted from the specific interaction between fucoidan and overexpressed p-selectin receptors.The excellent tumor-homing ability and MRI-guided chemo-photothermal therapy therefore endowed FMPDA/Gd^(3+)/DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality.Overall,our study demonstrated that FMPDA/Gd^(3+)/DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics.
基金supported by the National Natural Science Foundation of China (22104073)the Natural Science Foundation of Shandong (ZR2021QB119, 2022HWYQ-079)the Youth Innovation Science and Technology Program of Shandong Provincial Universities (2021KJ100)。
文摘Nanomedicine has become an important development direction of modern medicine, and provides a new way for cancer theranostics. To extend the superior physicochemical property of nanomedicine and enhance their role in cancer theranostics,various strategies have been proposed. Among them, the introduction of oxygen vacancies can enhance the separation of electron-hole pairs and improve the nanomaterials' catalytic activity, which is beneficial for cancer diagnosis and treatment. This review briefly summarized the formation mechanism and preparation methods of various oxygen vacancy nanomaterials. Then,the effect and application of various oxygen vacancy nanomaterials, such as iron, manganese, titanium, zinc, bismuth, tungsten,cerium, and molybdenum-based nanomaterials in enhancing cancer theranostics were highlighted. At last, the prospect and challenges of oxygen vacancy nanomaterials were discussed. This review provided an overview of the relevant information on oxygen vacancy in cancer theranostics, and further promoted the development of cancer nanomedicine.
基金supported by the Vanke Special Fund for Public Health and Health Discipline Development,Tsinghua University(2022Z82WKJ005,2022Z82WKJ013)the Tsinghua University Spring Breeze Fund(2021Z99CFZ007)+2 种基金the National Natural Science Foundation of China(22175107)Funding by Tsinghua Universitythe Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(SN-ZJU-SIAS-006)。
文摘The clinical translation of nanomedicines has been strongly hampered by the limitations of delivery vehicles,promoting scientists to search for novel nanocarriers.Although cell membrane-based delivery systems have attracted extensive attention,further functionalizations are urgently desired to augment their theranostic functions.We propose a cell-friendly supramolecular strategy to engineer cell membranes utilizing cyclodextrin-based host–guest molecular recognitions to fix the defects arising from chemical and genetic modifcations.In this study,the supramolecular cell membrane vesicles(SCMVs)specifcally accumulate in tumors,benefting from tumor-homing capability and the enhanced permeability and retention effect.SCMVs co-delivering indocyanine green and an indoleamine 2,3-dioxygenase inhibitor effectively ablate tumors combining photodynamic therapy and immunotherapy.Driven by host–guest inclusion complexation,SCMVs successfully encapsulate resiquimod to repolarize tumor-associated macrophages into M1 phenotype,synergizing with immune checkpoint blockade therapy.This supramolecular engineering methodology based on noncovalent interactions presents a generalizable and cell-friendly tactic to develop living cell–originated nanomaterials for precise cancer therapy.
基金This work was financially supported by the National Natural Science Foundation of China(Grant Nos.51773162 and 21204071).
文摘The design and development of multifunctional nano-drug delivery systems(NDDSs)is a solution that is expected to solve some intractable problems in traditional cancer treatment.In particular,metal-organic frameworks(MOFs)are novel hybrid porous nanomaterials which are constructed by the coordination of metal cations or clusters and organic bridging ligands.Benefiting from their intrinsic superior properties,MOFs have captivated intensive attentions in drug release and cancer theranostic.Based on what has been achieved about MOF-based DDSs in recent years,this review introduces different stimuli-responsive mechanisms of them and their applications in cancer diagnosis and treatment systematically.Moreover,the existing challenges and future opportunities in this field are summarized.By realizing industrial production and paying attention to biosafety,their clinical applications will be enriched.
基金supported by the National Natural Science Foundation of China (22171219, 22222112)the Innovation Talent Promotion Plan of Shaanxi Province for Science and Technology Innovation Team (2023-CX-TD-51)the Fundamental Research Funds for the Central Universities。
文摘Owing to their appealing three-dimensional structures and tunable photophysical properties, emissive metallacages have been widely applied in recognition and sensing, adsorption and separation, catalysis, etc. Recently, the application of emissive metallacages in biomedical fields has emerged as a hot research topic, because multiple biological functionalities can be facilely integrated into metallacage-based platforms to deliver different functions. In this review, the applications of emissive metallacages in bio-imaging, delivery and cancer theranostics are systematically summarized. The dilemmas and challenges of metallacage-based biomedical materials are also raised at the end of this review. We hope this review would provide some guidance for the construction of novel emissive metallacages with biological functions, and further advance the development of emissive metallacages as biomedical materials.
基金National Natural Science Foundation of China,Grant/Award Numbers:21890741,21974064,22022405Natural Science Foundation of Jiangsu Province,Grant/Award Number:BK20200010State Key Laboratory of Analytical Chemistry for Life Sciences,Grant/Award Numbers:5431ZZXM2204,5431ZZXM2307。
文摘The optical nanoprobes with emissions in the second near-infrared window(NIR-Ⅱ,1000-1700 nm)show low tissue autofluorescence and photon scattering;therefore,they provide high spatial resolution and acceptable tissue penetration depth.These advantages make them appropriate for in vivo applications,including bioimaging,NIR-Ⅱtriggered disease therapy,and even on-site efficacy monitoring.Among the various developed NIR-Ⅱfluorescence probes,lanthanide-doped nanoparticles(LDNPs)exhibit high photo stability and narrow emission bandwidths with long photoluminescence lifetimes and low cytotoxicity;therefore,they have been widely studied in the biomedical field.This review summarizes the typical compositions and optical properties of recently developed NIR-Ⅱemitting LDNPs.Their applications in in vivo NIR-Ⅱbioimaging and cancer therapy are reviewed.The perspectives and challenges of NIR-ⅡLDNPs are also discussed.
基金This article was partially supported by the National Basic Research Programs of China （973 Program） （No. 2016YFA0201200）, the National Natural Science Foundation of China （No. 51525203）, Collaborative Innovation Center of Suzhou Nano Science and Technology, and a Project Funded by the Priority Academic Program Development （PAPD） of Jiangsu Higher Education Institutions.
文摘The use of near-infrared （NIR） light for photodynamic therapy （PDT） is a promising strategy to circumvent the limitations of current PDT, in which visible light with limited tissue penetration depth is usually used. In the present stud~ alkyl thiolated gold nanoclusters （AuNCs） were co-modified with human serum albumin （HSA） and catalase （CAT）, and then employed as a multifunctional, optical, theranostic nano-agent. In the AuNC@HSA/CAT system, the AuNCs were able to produce singlet oxygen under excitation by a 1,064-nm laser, which locates in the second NIR window （NIR-II）, and featured much lower tissue absorption and scattering, enabling NIR-II-triggered PDT. The HSA coating greatly improved the physiological stability of the nanoparticles, which showed efficient tumor retention after intravenous injection, as revealed by detecting the AuNC fluorescence. Moreover, the presence of CAT in the nanoparticles triggered decomposition of tumor endogenous H202 to generate oxygen, thereby enhancing the efficacy of PDT by relieving tumor hypoxia. Compared with conventional PDT using visible light, NIR-II-triggered PDT exhibits remarkably increased tissue penetration. Thus, we developed a new type of photosensitizing nano-agent that simultaneously enables in vivo fluorescence imaging, tumor hypoxia relief, and NIR-II light-induced in vivo PDT in the treatment of cancer.
