Optical imaging plays an important role in biomedical research being extremely useful for early detection, screening and image-guided therapy. Lanthanide-doped up-converting nanoparticles were ideally suited for bioim...Optical imaging plays an important role in biomedical research being extremely useful for early detection, screening and image-guided therapy. Lanthanide-doped up-converting nanoparticles were ideally suited for bioimaging because they could be ex- cited in near infrared （NIR） and emit in NIR or visible （VIS）. Here, we compared lanthanide doped up-converting NaYF4 and organic fluorophores for application in deep-tissue imaging. For that purpose - tissue phantoms mimicking the natural properties of light scat- tering by living tissues were prepared. The studies allowed to quantitatively compare optical resolution of different fluorescent com- pounds, revealing that the NIR photoexcitation was favorable over conventional UV photoexcitation.展开更多
The combination of upconverting nanoparticles(UCNPs)and immunochromatography has become a widely used and promising new detection technique for point-of-care testing(POCT).However,their low luminescence efficiency,non...The combination of upconverting nanoparticles(UCNPs)and immunochromatography has become a widely used and promising new detection technique for point-of-care testing(POCT).However,their low luminescence efficiency,non-specific adsorption,and image noise have always limited their progress toward practical applications.Recently,artificial intelligence(AI)has demonstrated powerful representational learning and generalization capabilities in computer vision.We report for the first time a combination of AI and upconversion nanoparticle-based lateral flow assays(UCNP-LFAs)for the quantitative detection of commercial internet of things(IoT)devices.This universal UCNPs quantitative detection strategy combines high accuracy,sensitivity,and applicability in the field detection environment.By using transfer learning to train AI models in a small self-built database,we not only significantly improved the accuracy and robustness of quantitative detection,but also efficiently solved the actual problems of data scarcity and low computing power of POCT equipment.Then,the trained AI model was deployed in IoT devices,whereby the detection process does not require detailed data preprocessing to achieve real-time inference of quantitative results.We validated the quantitative detection of two detectors using eight transfer learning models on a small dataset.The AI quickly provided ultra-high accuracy prediction results(some models could reach 100%accuracy)even when strong noise was added.Simultaneously,the high flexibility of this strategy promises to be a general quantitative detection method for optical biosensors.We believe that this strategy and device have a scientific significance in revolutionizing the existing POCT technology landscape and providing excellent commercial value in the in vitro diagnostics(IVD)industry.展开更多
Oxygen sensing,magnetic,and upconversion luminescence properties are combined in multi-functional composite particles prepared herein by a simple mixing,baking,and grinding procedure.Upconverting nanocrystals are used...Oxygen sensing,magnetic,and upconversion luminescence properties are combined in multi-functional composite particles prepared herein by a simple mixing,baking,and grinding procedure.Upconverting nanocrystals are used as an excitation source and an oxygen indicator with far-red emission.The composite particles are excited with near infrared(NIR)laser light(980 nm).The visible upconversion emission is converted into an oxygen concentration-dependent far-red emission(<750 nm)using an inert mediator dye and a platinated benzoporphyrin dye.This concept combines the advantages of NIR excitation and far-red emissive indicator dyes,offering minimized auto-fluorescence and enhanced membrane permeability.Additional functionality is obtained by incorporating magnetic nanoparticles into the composite particles,which enables easy manipulation and separation of the particles by the application of an external magnetic field.展开更多
Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug de-Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug delivery. However, it remains a challe...Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug de-Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug delivery. However, it remains a challenge to localize and control drug release while retaining macrophage activity and exerting its immunotherapeutic effect. Herein, a localized light-triggered release macrophage cytopharmaceutical (USIP@M) was proposed, which could utilize the tumor targeting and immunotherapy effects of macrophages to reverse the immune suppression of tumor microenvironment (TME). Amphiphilic block copolymers with ultraviolet (UV)-responsive o-nitrobenzyl groups were synthesized and co-loaded with sorafenib (SF), IMD-0354 (IMD), and upconverting nanoparticles (UCNPs), which were then taken up by macrophages, and the targeted delivery of drugs was realized by using the tumor tropism of macrophages. UCNPs converted near-infrared light with strong penetrability and high safety into UV light, which promoted the photoresponsive depolymerization of block copolymers and production of exosomes from USIP@M, accelerated drug efflux and maintained the activity of macrophages. IMD simultaneously polarized carrier macrophages and tumor-associated macrophages to exert the antitumor effect of macrophages, enhance T cell immunity, and alleviate the immunosuppressive state of TME. Synergistically with the chemotherapeutic effect of SF, it could effectively kill tumors. In conclusion, based on the localized light-triggered release strategy, this study constructed a novel macrophage cytopharmaceutical that could localize and control drug release while retaining the activity of macrophages and exerting its immunotherapeutic effect, which could effectively treat solid tumors.展开更多
Synaptic vesicle transport by motor proteins along microtubules is a crucially active process underlying neuronal communication.It is known that microtubules are destabilized by tau-hyperphosphorylation,which causes t...Synaptic vesicle transport by motor proteins along microtubules is a crucially active process underlying neuronal communication.It is known that microtubules are destabilized by tau-hyperphosphorylation,which causes tau proteins to detach from microtubules and form neurofibril tangles.However,how tauphosphorylation affects the transport dynamics of motor proteins on the microtubule remains unknown.Here,we discover that the long-distance unidirectional motion of vesicle-motor protein multiplexes(VMPMs)in living cells is suppressed under tauhyperphosphorylation,with the consequent loss of fast vesicletransport along the microtubule.The VMPMs in hyperphosphorylated cells exhibit seemingly bidirectional random motion,with dynamic properties far different from those of VMPM motion in normal cells.We establish a parsimonious physicochemical model of VMPM’s active motion that provides a unified,quantitative explanation and predictions for our experimental results.Our analysis reveals that,under hyperphosphorylation conditions,motor protein multiplexes have both static and dynamic motility fluctuations.The loss of fast vesicle-transport along the microtubule can be a mechanism of neurodegenerative disorders associated with tau-hyperphosphorylation.展开更多
基金Project supported by Wroclaw Research Centre EIT+within the project"The Application of Nanotechnology in Advanced Materials"-NanoMat(POIG.01.01.02-02-002/08)financed by the European Regional Development Fund(Operational Programme Innovative Economy,1.1.2)
文摘Optical imaging plays an important role in biomedical research being extremely useful for early detection, screening and image-guided therapy. Lanthanide-doped up-converting nanoparticles were ideally suited for bioimaging because they could be ex- cited in near infrared （NIR） and emit in NIR or visible （VIS）. Here, we compared lanthanide doped up-converting NaYF4 and organic fluorophores for application in deep-tissue imaging. For that purpose - tissue phantoms mimicking the natural properties of light scat- tering by living tissues were prepared. The studies allowed to quantitatively compare optical resolution of different fluorescent com- pounds, revealing that the NIR photoexcitation was favorable over conventional UV photoexcitation.
基金The authors thank the financial support from the National Natural Science Foundation of China(61905033 and 62122017).
文摘The combination of upconverting nanoparticles(UCNPs)and immunochromatography has become a widely used and promising new detection technique for point-of-care testing(POCT).However,their low luminescence efficiency,non-specific adsorption,and image noise have always limited their progress toward practical applications.Recently,artificial intelligence(AI)has demonstrated powerful representational learning and generalization capabilities in computer vision.We report for the first time a combination of AI and upconversion nanoparticle-based lateral flow assays(UCNP-LFAs)for the quantitative detection of commercial internet of things(IoT)devices.This universal UCNPs quantitative detection strategy combines high accuracy,sensitivity,and applicability in the field detection environment.By using transfer learning to train AI models in a small self-built database,we not only significantly improved the accuracy and robustness of quantitative detection,but also efficiently solved the actual problems of data scarcity and low computing power of POCT equipment.Then,the trained AI model was deployed in IoT devices,whereby the detection process does not require detailed data preprocessing to achieve real-time inference of quantitative results.We validated the quantitative detection of two detectors using eight transfer learning models on a small dataset.The AI quickly provided ultra-high accuracy prediction results(some models could reach 100%accuracy)even when strong noise was added.Simultaneously,the high flexibility of this strategy promises to be a general quantitative detection method for optical biosensors.We believe that this strategy and device have a scientific significance in revolutionizing the existing POCT technology landscape and providing excellent commercial value in the in vitro diagnostics(IVD)industry.
基金This research was funded by Austrian Science Fund(FWF,I 442-N19)Deutsche Forschungsgemeinschaft(DFG,WO 669/12-1),both within the framework of an ERA Chemistry project.
文摘Oxygen sensing,magnetic,and upconversion luminescence properties are combined in multi-functional composite particles prepared herein by a simple mixing,baking,and grinding procedure.Upconverting nanocrystals are used as an excitation source and an oxygen indicator with far-red emission.The composite particles are excited with near infrared(NIR)laser light(980 nm).The visible upconversion emission is converted into an oxygen concentration-dependent far-red emission(<750 nm)using an inert mediator dye and a platinated benzoporphyrin dye.This concept combines the advantages of NIR excitation and far-red emissive indicator dyes,offering minimized auto-fluorescence and enhanced membrane permeability.Additional functionality is obtained by incorporating magnetic nanoparticles into the composite particles,which enables easy manipulation and separation of the particles by the application of an external magnetic field.
基金National Natural Science Foundation of China(82373809,82173756,82173757)Shandong Excellent Youth Fund(ZR2022YQ76,China).
文摘Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug de-Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug delivery. However, it remains a challenge to localize and control drug release while retaining macrophage activity and exerting its immunotherapeutic effect. Herein, a localized light-triggered release macrophage cytopharmaceutical (USIP@M) was proposed, which could utilize the tumor targeting and immunotherapy effects of macrophages to reverse the immune suppression of tumor microenvironment (TME). Amphiphilic block copolymers with ultraviolet (UV)-responsive o-nitrobenzyl groups were synthesized and co-loaded with sorafenib (SF), IMD-0354 (IMD), and upconverting nanoparticles (UCNPs), which were then taken up by macrophages, and the targeted delivery of drugs was realized by using the tumor tropism of macrophages. UCNPs converted near-infrared light with strong penetrability and high safety into UV light, which promoted the photoresponsive depolymerization of block copolymers and production of exosomes from USIP@M, accelerated drug efflux and maintained the activity of macrophages. IMD simultaneously polarized carrier macrophages and tumor-associated macrophages to exert the antitumor effect of macrophages, enhance T cell immunity, and alleviate the immunosuppressive state of TME. Synergistically with the chemotherapeutic effect of SF, it could effectively kill tumors. In conclusion, based on the localized light-triggered release strategy, this study constructed a novel macrophage cytopharmaceutical that could localize and control drug release while retaining the activity of macrophages and exerting its immunotherapeutic effect, which could effectively treat solid tumors.
基金supported by the grant awarded from GIST in 2020 through the Research Institute(GRI)program and by the National Research Foundation(NRF)of S.Korea(Grant no.2020R1F1A1073442,2021R1A2C2010557)J.S.was supported by the Creative Research Initiative Project Program(NRF-2015R1A3A2066497)+3 种基金the Engineering Research Center Program funded by the Korea government(MSIT)(NRF-2020R1A5A1018052)Y.H.S.,J.-H.K.,and M.H.L.were supported by the NRF[NRF-2019R1I1A1A01056975(Y.H.S.)NRF-2020R1A2C1102788(J.-H.K.)NRF-2022R1A3B1077319(M.H.L.)]。
文摘Synaptic vesicle transport by motor proteins along microtubules is a crucially active process underlying neuronal communication.It is known that microtubules are destabilized by tau-hyperphosphorylation,which causes tau proteins to detach from microtubules and form neurofibril tangles.However,how tauphosphorylation affects the transport dynamics of motor proteins on the microtubule remains unknown.Here,we discover that the long-distance unidirectional motion of vesicle-motor protein multiplexes(VMPMs)in living cells is suppressed under tauhyperphosphorylation,with the consequent loss of fast vesicletransport along the microtubule.The VMPMs in hyperphosphorylated cells exhibit seemingly bidirectional random motion,with dynamic properties far different from those of VMPM motion in normal cells.We establish a parsimonious physicochemical model of VMPM’s active motion that provides a unified,quantitative explanation and predictions for our experimental results.Our analysis reveals that,under hyperphosphorylation conditions,motor protein multiplexes have both static and dynamic motility fluctuations.The loss of fast vesicle-transport along the microtubule can be a mechanism of neurodegenerative disorders associated with tau-hyperphosphorylation.
