Massive efforts have been concentrated on the advance of eminent near-infrared(NIR) photothermal materials(PTMs) in the NIR-Ⅱ window(1000–1700 nm), especially organic PTMs because of their intrinsic biological safet...Massive efforts have been concentrated on the advance of eminent near-infrared(NIR) photothermal materials(PTMs) in the NIR-Ⅱ window(1000–1700 nm), especially organic PTMs because of their intrinsic biological safety compared with inorganic PTMs. However, so far, only a few NIR-Ⅱresponsive organic PTMs was explored, and their photothermal conversion efficiencies(PCEs) still remain relatively low. Herein, donor–acceptor conjugated diradical polymers with open-shell characteristics are explored for synergistically photothermal immunotherapy of metastatic tumors in the NIR-Ⅱ window. By employing side-chain regulation, the conjugated diradical polymer TTB-2 with obvious NIR-Ⅱ absorption was developed, and its nanoparticles realize a record-breaking PCE of 87.7% upon NIR-Ⅱ light illustration. In vitro and in vivo experiments demonstrate that TTB-2 nanoparticles show good tumor photoablation with navigation of photoacoustic imaging in the NIR-Ⅱ window, without any side-effect. Moreover, by combining with PD-1 antibody,the pulmonary metastasis of breast cancer is high-effectively prevented by the efficient photo-immunity effect. Thus, this study explores superior PTMs for cancer metastasis theranostics in the NIR-Ⅱ window, offering a new horizon in developing radical-characteristic NIR-Ⅱ photothermal materials.展开更多
Fluorescence imaging through the second near-infrared window(NIR-Ⅱ,1000–1700 nm) allows in-depth imaging.However, current imaging systems use wide-field illumination and can only provide low-contrast 2D information,...Fluorescence imaging through the second near-infrared window(NIR-Ⅱ,1000–1700 nm) allows in-depth imaging.However, current imaging systems use wide-field illumination and can only provide low-contrast 2D information, without depth resolution. Here, we systematically apply a light-sheet illumination, a time-gated detection, and a deep-learning algorithm to yield high-contrast high-resolution volumetric images. To achieve a large Fo V(field of view) and minimize the scattering effect, we generate a light sheet as thin as 100.5 μm with a Rayleigh length of 8 mm to yield an axial resolution of 220 μm. To further suppress the background, we time-gate to only detect long lifetime luminescence achieving a high contrast of up to 0.45 Icontrast. To enhance the resolution, we develop an algorithm based on profile protrusions detection and a deep neural network and distinguish vasculature from a low-contrast area of 0.07 Icontrast to resolve the 100μm small vessels. The system can rapidly scan a volume of view of 75 × 55 × 20 mm3and collect 750 images within 6mins. By adding a scattering-based modality to acquire the 3D surface profile of the mice skin, we reveal the whole volumetric vasculature network with clear depth resolution within more than 1 mm from the skin. High-contrast large-scale 3D animal imaging helps us expand a new dimension in NIR-Ⅱ imaging.展开更多
Second near-infrared(NIR-Ⅱ)light triggered in-situ tumor vaccination(ISTV)represents one of the most promising strategies in boosting the whole-body antitumor immunity.While most of previously developed nano-adjuvant...Second near-infrared(NIR-Ⅱ)light triggered in-situ tumor vaccination(ISTV)represents one of the most promising strategies in boosting the whole-body antitumor immunity.While most of previously developed nano-adjuvants for NIR-Ⅱ-triggered ISTV are“all-in-one”formulations,which may indiscriminately damage both the tumor cells and the immune cells,limiting the overall effect of immune response.To overcome this obstacle,we designed a“cocktail”nano-adjuvant by physically mixing hyaluronidases(HAase)-decorated gold nanostars(HA)for NIR-Ⅱlight triggered in situ production of tumor-associated antigens and CpG functionalized gold nanospheres(CA)for immune cells activation.Compared to“all-in-one”formulation,the“cocktail”nano-adjuvants displayed a significantly stronger immune response on NIR-Ⅱlight induced dendritic cells(DCs)mutation and T cells differentiation,greater effect on tumor-growth inhibition,and higher efficacy in inhibition of pulmonary metastases.What is more,increasing the molar ratio of HA to CA led to an enhanced anticancer immune responses.This study highlight the nano-adjuvant formulation effects on the treatment of tumors with multiple targets.展开更多
Ferroptosis(FPT),a novel form of programmed cell death,is characterized by overwhelming iron/reactive oxygen species(ROS)-dependent accumulation of lipid peroxidation(LPO).However,the insufficiency of endogenous iron ...Ferroptosis(FPT),a novel form of programmed cell death,is characterized by overwhelming iron/reactive oxygen species(ROS)-dependent accumulation of lipid peroxidation(LPO).However,the insufficiency of endogenous iron and ROS level limited the FPT therapeutic efficacy to a large extent.To overcome this obstacle,the bromodomain-containing protein 4(BRD_(4))-inhibitor(+)-JQ1(JQ1)and iron-supplement ferric ammonium citrate(FAC)-loaded gold nanorods(GNRs)are encapsulated into the zeolitic imidazolate framework-8(ZIF-8)to form matchbox-like GNRs@JF/ZIF-8 for the amplified FPT therapy.The existence of matchbox(ZIF-8)is stable in physiologically neutral conditions but degradable in acidic environment,which could prevent the loaded agents from prematurely reacting.Moreover,GNRs as the drug-carriers induce the photothermal therapy(PTT)effect under the irradiation of near-infraredⅡ(NIR-Ⅱ)light owing to the absorption by localized surface plasmon resonance(LSPR),while the hyperthermia also boosts the JQ1 and FAC releasing in the tumor microenvironment(TME).On one hand,the FAC-induced Fenton/Fenton-like reactions in TME can simultaneously generate iron(Fe^(3+)/Fe^(2+))and ROS to initiate the FPT treatment by LPO elevation.On the other hand,JQ1 as a small molecule inhibitor of BRD_(4)protein can amplify FPT through downregulating the expression of glutathione peroxidase 4(GPX4),thus inhibiting the ROS elimination and leading to the LPO accumulation.Both in vitro and in vivo studies reveal that this p H-sensitive nano-matchbox achieves obvious suppression of tumor growth with good biosafety and biocompatibility.As a result,our study points out a PTT combined iron-based/BRD_(4)-downregulated strategy for amplified ferrotherapy which also opens the door of future exploitation of ferrotherapy systems.展开更多
Gold nanoclusters(AuNCs)with near-infraredⅡ(NIR-Ⅱ)photoluminescence(PL)have emerged as novel bioimaging probes for in vivo disease diagnosis.So far,it still lacks a systematic review focusing on the synthesis,PL tun...Gold nanoclusters(AuNCs)with near-infraredⅡ(NIR-Ⅱ)photoluminescence(PL)have emerged as novel bioimaging probes for in vivo disease diagnosis.So far,it still lacks a systematic review focusing on the synthesis,PL tuning,and in vivo imaging of NIR-Ⅱluminescent AuNCs.In this review,we briefly introduce the synthesis of NIR-Ⅱluminescent AuNCs using various surface ligands.We discuss the origins and properties of NIR-ⅡPL in AuNCs,and summarize the strategies for improving and/or tuning NIR-ⅡPL emissions.We also provide an overview of the recent progress in the application of AuNCs in tumor-targeted imaging,molecular imaging,and other areas(such as the sensitive imaging of bones,vessels,lymph nodes,etc.).Finally,we present the prospects and challenges in the field of NIR-Ⅱluminescent AuNCs and related imaging applications,expecting to offer comprehensive understanding of this field,and thereby deepening and broadening the biological application of AuNCs.展开更多
Rare earth luminescence has attracted widespread attention for several decades, among which nearinfrared(NIR) light-related up-conversion luminescence and NIR-Ⅱ luminescence are widely used in the biomedical field. T...Rare earth luminescence has attracted widespread attention for several decades, among which nearinfrared(NIR) light-related up-conversion luminescence and NIR-Ⅱ luminescence are widely used in the biomedical field. The NIR-related luminescence is widely studied due to the excellent performance, such as good biocompatibility, deep tissue penetration depth, low self-fluorescence and minimal light damage to organisms. In this review, we mainly introduce the mechanism for rare earth up-conversion luminescence, NIR-Ⅱ luminescence and conclude their advantages compared with traditional luminescence.These excellent priorities provide the basis for NIR-related luminescence bioimaging in vivo. Additionally,we hilglight the scheme for the sensitive detection of substances in organisms and various methods for biological therapy. In spite of the existing research, it is outlined that NIR-related luminescence has great potential to be applied in different aspects, expanding perspectives and future challenges of research in related fields. Based on the current scientific achievements, this review can provide reference for research in the areas mentioned above, expand the research direction and arouse a broad interest in different disciplines to pay attention to rare earth luminescence.展开更多
Multimodal imaging in the second near-infrared window(NIR-II)guided cancer therapy is a highly precise and efficient cancer theranostic strategy.However,it is still a challenge to develop activated NIR-II optical imag...Multimodal imaging in the second near-infrared window(NIR-II)guided cancer therapy is a highly precise and efficient cancer theranostic strategy.However,it is still a challenge to develop activated NIR-II optical imaging and therapy agents.In this study,we develop a pH-responsive hybrid plasmonic-fluorescent vesicle by self-assembly of amphiphilic plasmonic nanogapped gold nanorod(AuNNR)and fluorescent down-conversion nanoparticles(DCNP)(AuNNR-DCNP Ve),showing remarkable and activated NIR-II fluorescence(FL)/NIR-II photoacoustic(PA)imaging performances.The hybrid vesicle also exhibited superior loading capacity of doxorubicin as a superior drug carrier and efficient radiosensitizer for X-ray-induced radiotherapy.Interestingly,the accumulated hybrid AuNNR-DCNP Ve in the tumor resulted in a recovery of NIR-II FL imaging signal and a variation in NIR-II PA imaging signal.Dual activated NIR-II PA and FL imaging of the hybrid vesicle could trace drug release and precisely guided cancer radiotherapy to ultimately reduce the side effects to healthy tissue.展开更多
It is challenging to develop molecular fluorophores in the second near-infrared(NIR-Ⅱ)window with long wavelength emission and high brightness,which can improve the performance of biological imaging.Herein,we report ...It is challenging to develop molecular fluorophores in the second near-infrared(NIR-Ⅱ)window with long wavelength emission and high brightness,which can improve the performance of biological imaging.Herein,we report a molecular engineering approach to afford NIR-Ⅱ fluorophores with these merits based on fused-ring acceptor(FRA)molecules.Dioctyl 3,4-propylenedioxy thiophene(PDOT-C8)is utilized as the bridging donor to replace 3-ethylhexyloxy thiophene(3-EHOT),leading to more than 20 times enhancement of brightness.The nanofluorophores(NFs)based on the optimized CPTIC-4F molecule exhibit an emission peak of 1,110 nm with a fluorescence quantum yield(QY)of 0.39%(QY of IR-26 is 0.050%in dichloroethane as reference)and peak absorption coefficient of 14.5 x 10^4 M^-1·cm^-1 in aqueous solutions,which are significantly higher than those of 3-EHOT based COTIC-4F NFs.It is found that PDOT-C8 can weaken intermolecular aggregation,enhance protection of molecular backbone from water,and decrease backbone distortion,beneficial for the high brightness.Compared with indocyanine green with same injection dose,CPTIC-4F NFs show 10 times higher signal-to-background ratio for whole body vessels imaging at 1,300 nm long pass filters.展开更多
基金The work was financially supported by the National Natural Science Foundation of China(No.52173135,22207024)Jiangsu Specially Appointed Professorship,Leading Talents of Innovation and Entrepreneurship of Gusu(ZXL2022496)the Suzhou Science and Technology Program(SKY2022039).
文摘Massive efforts have been concentrated on the advance of eminent near-infrared(NIR) photothermal materials(PTMs) in the NIR-Ⅱ window(1000–1700 nm), especially organic PTMs because of their intrinsic biological safety compared with inorganic PTMs. However, so far, only a few NIR-Ⅱresponsive organic PTMs was explored, and their photothermal conversion efficiencies(PCEs) still remain relatively low. Herein, donor–acceptor conjugated diradical polymers with open-shell characteristics are explored for synergistically photothermal immunotherapy of metastatic tumors in the NIR-Ⅱ window. By employing side-chain regulation, the conjugated diradical polymer TTB-2 with obvious NIR-Ⅱ absorption was developed, and its nanoparticles realize a record-breaking PCE of 87.7% upon NIR-Ⅱ light illustration. In vitro and in vivo experiments demonstrate that TTB-2 nanoparticles show good tumor photoablation with navigation of photoacoustic imaging in the NIR-Ⅱ window, without any side-effect. Moreover, by combining with PD-1 antibody,the pulmonary metastasis of breast cancer is high-effectively prevented by the efficient photo-immunity effect. Thus, this study explores superior PTMs for cancer metastasis theranostics in the NIR-Ⅱ window, offering a new horizon in developing radical-characteristic NIR-Ⅱ photothermal materials.
基金Technology Program(KQTD20170810110913065,20200925174735005)National Natural Science Foundation of China(62005116,51720105015)Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022B1212010003).
文摘Fluorescence imaging through the second near-infrared window(NIR-Ⅱ,1000–1700 nm) allows in-depth imaging.However, current imaging systems use wide-field illumination and can only provide low-contrast 2D information, without depth resolution. Here, we systematically apply a light-sheet illumination, a time-gated detection, and a deep-learning algorithm to yield high-contrast high-resolution volumetric images. To achieve a large Fo V(field of view) and minimize the scattering effect, we generate a light sheet as thin as 100.5 μm with a Rayleigh length of 8 mm to yield an axial resolution of 220 μm. To further suppress the background, we time-gate to only detect long lifetime luminescence achieving a high contrast of up to 0.45 Icontrast. To enhance the resolution, we develop an algorithm based on profile protrusions detection and a deep neural network and distinguish vasculature from a low-contrast area of 0.07 Icontrast to resolve the 100μm small vessels. The system can rapidly scan a volume of view of 75 × 55 × 20 mm3and collect 750 images within 6mins. By adding a scattering-based modality to acquire the 3D surface profile of the mice skin, we reveal the whole volumetric vasculature network with clear depth resolution within more than 1 mm from the skin. High-contrast large-scale 3D animal imaging helps us expand a new dimension in NIR-Ⅱ imaging.
基金financially supported by the National Natural Science Foundation of China(No.52273163)the Science Technology and Innovation Commission of Shenzhen Municipality(No.JCYJ20190807163003704)Open Research Fund of Jiangsu Key Laboratory of Environmentally Friendly Polymeric Materials(No.PML2201)。
文摘Second near-infrared(NIR-Ⅱ)light triggered in-situ tumor vaccination(ISTV)represents one of the most promising strategies in boosting the whole-body antitumor immunity.While most of previously developed nano-adjuvants for NIR-Ⅱ-triggered ISTV are“all-in-one”formulations,which may indiscriminately damage both the tumor cells and the immune cells,limiting the overall effect of immune response.To overcome this obstacle,we designed a“cocktail”nano-adjuvant by physically mixing hyaluronidases(HAase)-decorated gold nanostars(HA)for NIR-Ⅱlight triggered in situ production of tumor-associated antigens and CpG functionalized gold nanospheres(CA)for immune cells activation.Compared to“all-in-one”formulation,the“cocktail”nano-adjuvants displayed a significantly stronger immune response on NIR-Ⅱlight induced dendritic cells(DCs)mutation and T cells differentiation,greater effect on tumor-growth inhibition,and higher efficacy in inhibition of pulmonary metastases.What is more,increasing the molar ratio of HA to CA led to an enhanced anticancer immune responses.This study highlight the nano-adjuvant formulation effects on the treatment of tumors with multiple targets.
基金supported by Foundation Young Elite Scientists Sponsorship Program by Tianjin(0701320001,China)Major Special Projects of Tianjin(No.0402080005,China)+2 种基金the National Natural Science Foundation of China(No.81771880 and No.82171989,China)National Natural Science Foundation of China(No.82171989,China)Applied Basic Research of Tianjin(No.21JCYBJC00660,China)。
文摘Ferroptosis(FPT),a novel form of programmed cell death,is characterized by overwhelming iron/reactive oxygen species(ROS)-dependent accumulation of lipid peroxidation(LPO).However,the insufficiency of endogenous iron and ROS level limited the FPT therapeutic efficacy to a large extent.To overcome this obstacle,the bromodomain-containing protein 4(BRD_(4))-inhibitor(+)-JQ1(JQ1)and iron-supplement ferric ammonium citrate(FAC)-loaded gold nanorods(GNRs)are encapsulated into the zeolitic imidazolate framework-8(ZIF-8)to form matchbox-like GNRs@JF/ZIF-8 for the amplified FPT therapy.The existence of matchbox(ZIF-8)is stable in physiologically neutral conditions but degradable in acidic environment,which could prevent the loaded agents from prematurely reacting.Moreover,GNRs as the drug-carriers induce the photothermal therapy(PTT)effect under the irradiation of near-infraredⅡ(NIR-Ⅱ)light owing to the absorption by localized surface plasmon resonance(LSPR),while the hyperthermia also boosts the JQ1 and FAC releasing in the tumor microenvironment(TME).On one hand,the FAC-induced Fenton/Fenton-like reactions in TME can simultaneously generate iron(Fe^(3+)/Fe^(2+))and ROS to initiate the FPT treatment by LPO elevation.On the other hand,JQ1 as a small molecule inhibitor of BRD_(4)protein can amplify FPT through downregulating the expression of glutathione peroxidase 4(GPX4),thus inhibiting the ROS elimination and leading to the LPO accumulation.Both in vitro and in vivo studies reveal that this p H-sensitive nano-matchbox achieves obvious suppression of tumor growth with good biosafety and biocompatibility.As a result,our study points out a PTT combined iron-based/BRD_(4)-downregulated strategy for amplified ferrotherapy which also opens the door of future exploitation of ferrotherapy systems.
基金supported by the National Key Research&Development Program of China(2020YFA0709900)the National Natural Science Foundation of China(22027805,22274024)+2 种基金the Major Project of Science and Technology of Fujian Province(2020HZ06006)the Young Elite Scientist Sponsorship Program by CAST(YESS20200110)China Postdoctoral Science Foundation(2022M720737,2021T140117)
文摘Gold nanoclusters(AuNCs)with near-infraredⅡ(NIR-Ⅱ)photoluminescence(PL)have emerged as novel bioimaging probes for in vivo disease diagnosis.So far,it still lacks a systematic review focusing on the synthesis,PL tuning,and in vivo imaging of NIR-Ⅱluminescent AuNCs.In this review,we briefly introduce the synthesis of NIR-Ⅱluminescent AuNCs using various surface ligands.We discuss the origins and properties of NIR-ⅡPL in AuNCs,and summarize the strategies for improving and/or tuning NIR-ⅡPL emissions.We also provide an overview of the recent progress in the application of AuNCs in tumor-targeted imaging,molecular imaging,and other areas(such as the sensitive imaging of bones,vessels,lymph nodes,etc.).Finally,we present the prospects and challenges in the field of NIR-Ⅱluminescent AuNCs and related imaging applications,expecting to offer comprehensive understanding of this field,and thereby deepening and broadening the biological application of AuNCs.
基金Financial support from the National Natural Science Foundation of China(NSFC,Nos.51972076,52272144,22205048)the Heilongjiang Provincial Natural Science Foundation of China(No.JQ2022E001)+3 种基金the Natural Science Foundation of Shandong Province(No.ZR2020ZD42)Project funded by China Postdoctoral Science Foundation(No.2022M710931)the Fundamental Research Funds for the Central Universitiesthe Special Scientific Research Starting Foundation for Young teachers of Zhengzhou University(No.32213226).
文摘Rare earth luminescence has attracted widespread attention for several decades, among which nearinfrared(NIR) light-related up-conversion luminescence and NIR-Ⅱ luminescence are widely used in the biomedical field. The NIR-related luminescence is widely studied due to the excellent performance, such as good biocompatibility, deep tissue penetration depth, low self-fluorescence and minimal light damage to organisms. In this review, we mainly introduce the mechanism for rare earth up-conversion luminescence, NIR-Ⅱ luminescence and conclude their advantages compared with traditional luminescence.These excellent priorities provide the basis for NIR-related luminescence bioimaging in vivo. Additionally,we hilglight the scheme for the sensitive detection of substances in organisms and various methods for biological therapy. In spite of the existing research, it is outlined that NIR-related luminescence has great potential to be applied in different aspects, expanding perspectives and future challenges of research in related fields. Based on the current scientific achievements, this review can provide reference for research in the areas mentioned above, expand the research direction and arouse a broad interest in different disciplines to pay attention to rare earth luminescence.
基金supported by the National Natural Science Foundation of China (21971185 and 52173177)the Natural Science Foundation of Jiangsu Province (BK20230010 and BK20221362)+4 种基金the Science and Technology Support Program of Jiangsu Province (TJ-2022-002)funded by the Collaborative Innovation Center of Suzhou Nano Science&Technologythe 111 Projectthe Joint International Research Laboratory of Carbon-Based Functional Materials and DevicesSoochow University Tang Scholar。
基金This work was supported by the National Natural Science Foundation of China(Nos.21635002 and 21874024)the joint research projects of Health and Education Commission of Fujian Province(No.2019-WJ-20).
文摘Multimodal imaging in the second near-infrared window(NIR-II)guided cancer therapy is a highly precise and efficient cancer theranostic strategy.However,it is still a challenge to develop activated NIR-II optical imaging and therapy agents.In this study,we develop a pH-responsive hybrid plasmonic-fluorescent vesicle by self-assembly of amphiphilic plasmonic nanogapped gold nanorod(AuNNR)and fluorescent down-conversion nanoparticles(DCNP)(AuNNR-DCNP Ve),showing remarkable and activated NIR-II fluorescence(FL)/NIR-II photoacoustic(PA)imaging performances.The hybrid vesicle also exhibited superior loading capacity of doxorubicin as a superior drug carrier and efficient radiosensitizer for X-ray-induced radiotherapy.Interestingly,the accumulated hybrid AuNNR-DCNP Ve in the tumor resulted in a recovery of NIR-II FL imaging signal and a variation in NIR-II PA imaging signal.Dual activated NIR-II PA and FL imaging of the hybrid vesicle could trace drug release and precisely guided cancer radiotherapy to ultimately reduce the side effects to healthy tissue.
基金Y.L.acknowledges financial supports from the National Natural Science Foundation of China(No.21772084)Fundamental Research Layout of Shenzhen(No.JCY20180504165657443)+2 种基金H.S.thanks the National Natural Science Foundation of China(Nos.11727810,61720106009 and 21603074)the Science and Technology Commission of Shanghai Municipality(No.19JC1412200)for funding support and the ECNU Multifunctional Platform for Innovation(001)and HPC Research Computing Team for providing computational and storage resourcesX.Z thanks the funding supports from the National Natural Science Foundation of China(Nos.91859101,81971744,and U1932107).
文摘It is challenging to develop molecular fluorophores in the second near-infrared(NIR-Ⅱ)window with long wavelength emission and high brightness,which can improve the performance of biological imaging.Herein,we report a molecular engineering approach to afford NIR-Ⅱ fluorophores with these merits based on fused-ring acceptor(FRA)molecules.Dioctyl 3,4-propylenedioxy thiophene(PDOT-C8)is utilized as the bridging donor to replace 3-ethylhexyloxy thiophene(3-EHOT),leading to more than 20 times enhancement of brightness.The nanofluorophores(NFs)based on the optimized CPTIC-4F molecule exhibit an emission peak of 1,110 nm with a fluorescence quantum yield(QY)of 0.39%(QY of IR-26 is 0.050%in dichloroethane as reference)and peak absorption coefficient of 14.5 x 10^4 M^-1·cm^-1 in aqueous solutions,which are significantly higher than those of 3-EHOT based COTIC-4F NFs.It is found that PDOT-C8 can weaken intermolecular aggregation,enhance protection of molecular backbone from water,and decrease backbone distortion,beneficial for the high brightness.Compared with indocyanine green with same injection dose,CPTIC-4F NFs show 10 times higher signal-to-background ratio for whole body vessels imaging at 1,300 nm long pass filters.
基金supported by the National Key Research and Development Program of China(2017YFC1309100 and 2017YFA0205200)the National Natural Science Foundation of China(21804104 and 91959124)+2 种基金the Research Fund of the State Key Laboratory of Solidification Processing(NPU,2020-QZ-01)the Fundamental Research Fund for the Central University(3102019jcc005)the Youth Innovation Team of Shaanxi Universities,Natural Science Foundation of Shaanxi Province(2020PT-020)。
