Red blood cells(RBCs)have recently emerged as promosing candidates for cancer treatment in terms of relieving tumor hypoxia and inducing oxidative damage against cancer cells,but they are still far from satisfactory d...Red blood cells(RBCs)have recently emerged as promosing candidates for cancer treatment in terms of relieving tumor hypoxia and inducing oxidative damage against cancer cells,but they are still far from satisfactory due to their limited oxygen transport and reactive oxygen species generation rate in tumor tissue.Herein,artificial RBCs(designated FTP@RBCM)with radical storm production ability were developed for oncotherapy through multidimensional reactivity pathways of Fe-protoporphyrin-based hybrid metal-organic frameworks(FTPs,as the core),including photodynamic/chemodynamic-like,catalase-like and glutathione peroxidase-like activities.Meanwhile,owing to the advantages of long circulation abilities of RBCs provided by their cell membranes(RBCMs),FTP with a surface coated with RBCMs(FTP@RBCM)could enormously accumulate at tumor site to achieve remarkably enhanced therapeutic efficiency.Intriguingly,this ROS-mediated dynamic therapy was demonstrated to induce acute local inflammation and high immunogenic cancer death,which evoked a systemic antitumor immune response when combined with the newly identified T cell immunoglobulin and mucin-containing molecule 3(Tim-3)checkpoint blockade,leading to not only effective elimination of primary tumors but also an abscopal effect of growth suppression of distant tumors.Therefore,such RBC-mimic nanocatalysts with multidimensional catalytic capacities might provide a promising new insight into synergistic cancer treatment.展开更多
Photodynamic therapy(PDT)is a promising cancer treatment that uses photosensitizers(PSs)to generate cytotoxic reactive oxygen species(ROS)under light;but improving its efficacy is crucial for clinical applications.To ...Photodynamic therapy(PDT)is a promising cancer treatment that uses photosensitizers(PSs)to generate cytotoxic reactive oxygen species(ROS)under light;but improving its efficacy is crucial for clinical applications.To address this;we propose a smart nanoplatform(P@BAO-DOX)for synergistic chemo-photodynamic therapy;featuring efficient PDT;controllable drug release;and fluorescence imaging guidance.We designed an aggregation-induced emission(AIE)-based PS(BAO)with effective ROS generation and NIR-II fluorescence.Additionally;BAO as a PS and doxorubicin(DOX)as a chemo drug were encapsulated in p H-responsive nanogels(PNA)to obtain P@BAO-DOX nanogels.Upon uptake by tumor cells;the nanogel releases drugs in acidic conditions;leading to cell death.White light irradiation further triggers BAO to produce substantial ROS;enhancing phototoxicity and synergistic chemo-PDT cancer therapy.Thus;P@BAO-DOX nanogels;as a smart nanoplatform;offer precise drug release and efficient ROS generation for imaging-guided chemo-PDT synergistic therapy;showing promise in advancing cancer treatment.展开更多
Scattering media pose a significant barrier to non-invasive biomedical imaging,as conventional wavefront shaping methods rely on invasive guide stars or costly nonlinear modalities.Here,we introduce an improved approa...Scattering media pose a significant barrier to non-invasive biomedical imaging,as conventional wavefront shaping methods rely on invasive guide stars or costly nonlinear modalities.Here,we introduce an improved approach that enables high-fidelity,non-invasive fluorescence imaging through scattering media by combining the linear fluorescence mechanism with efficient computational optimization.The method leverages a genetic algorithm guided by variance maximization to dynamically optimize speckle,non-invasively exciting an individual fluorescent bead by∼10-fold enhancement in target intensity ratio.This process generates a precise system point spread function(PSF),which drives a convex optimization-based deconvolution framework to reconstruct obscured targets.Remarkably,the technique eliminates the need for complex scanning systems,achieving rapid wide-field imaging with structural similarity(SSIM)indices exceeding 0.997(for beads).We demonstrate robust imaging of both discrete beads and continuous fibers behind scattering media,revealing resolution superior to that of conventional speckle cross-correlation methods.The method provides a pathway for non-invasively visualizing fluorescent objects behind scattering media.展开更多
Systematic administration of small molecular drugs often suffered from the low efficacy and systemic toxicity in cancer therapy.In addition,application of single mode drug usually leads to unsatisfactory therapeutic o...Systematic administration of small molecular drugs often suffered from the low efficacy and systemic toxicity in cancer therapy.In addition,application of single mode drug usually leads to unsatisfactory therapeutic out-comes.Currently,developing multimodal-drug combination strategy that acts on different pathways without increasing side effects remains great challenge.Here,we developed a hydrogel system that co-delivered glycolysis inhibitor apigenin and chemo-drug gemcitabine to realize combination strategy for combating can-cer with minimal systemic toxicity.We demonstrated that this system can not only eliminate tumor cells in situ,but also induce abscopal effect on various tumor models.These results showed that our study provided a safe and effective strategy for clinical cancer treatment.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.62175198)the Natural Science Foundation of Fujian Province of China(Grant No.2020J02010)+1 种基金the Joint Funds for the innovation of science and Technology,Fujian province(Grant No.2019Y9046)the Fundamental Research Funds for the Central Universities(Grant No.xzy022020037).
文摘Red blood cells(RBCs)have recently emerged as promosing candidates for cancer treatment in terms of relieving tumor hypoxia and inducing oxidative damage against cancer cells,but they are still far from satisfactory due to their limited oxygen transport and reactive oxygen species generation rate in tumor tissue.Herein,artificial RBCs(designated FTP@RBCM)with radical storm production ability were developed for oncotherapy through multidimensional reactivity pathways of Fe-protoporphyrin-based hybrid metal-organic frameworks(FTPs,as the core),including photodynamic/chemodynamic-like,catalase-like and glutathione peroxidase-like activities.Meanwhile,owing to the advantages of long circulation abilities of RBCs provided by their cell membranes(RBCMs),FTP with a surface coated with RBCMs(FTP@RBCM)could enormously accumulate at tumor site to achieve remarkably enhanced therapeutic efficiency.Intriguingly,this ROS-mediated dynamic therapy was demonstrated to induce acute local inflammation and high immunogenic cancer death,which evoked a systemic antitumor immune response when combined with the newly identified T cell immunoglobulin and mucin-containing molecule 3(Tim-3)checkpoint blockade,leading to not only effective elimination of primary tumors but also an abscopal effect of growth suppression of distant tumors.Therefore,such RBC-mimic nanocatalysts with multidimensional catalytic capacities might provide a promising new insight into synergistic cancer treatment.
基金supported by the National Key Research and Development Program of China(2023YFB3810001)the National Natural Science Foundation of China(62175198,52333007,U22A2092,and 52273197)+4 种基金the Shenzhen Key Laboratory of Functional Aggregate Materials(ZDSYS20211021111400001)the Science,Technology and Innovation Commission of Shenzhen Municipality(JCYJ2021324134613038,KQTD20210811090142053,JCYJ20220818103007014,and GJHZ20210705141810031)the Innovation and Technology Commission(ITC-CNERC14SC01)the Science and Technology Program of Guangzhou,China(2023A04J0069)the Fundamental Research Funds for the Central Universities(xtr062022002 and xzy022022007).
文摘Photodynamic therapy(PDT)is a promising cancer treatment that uses photosensitizers(PSs)to generate cytotoxic reactive oxygen species(ROS)under light;but improving its efficacy is crucial for clinical applications.To address this;we propose a smart nanoplatform(P@BAO-DOX)for synergistic chemo-photodynamic therapy;featuring efficient PDT;controllable drug release;and fluorescence imaging guidance.We designed an aggregation-induced emission(AIE)-based PS(BAO)with effective ROS generation and NIR-II fluorescence.Additionally;BAO as a PS and doxorubicin(DOX)as a chemo drug were encapsulated in p H-responsive nanogels(PNA)to obtain P@BAO-DOX nanogels.Upon uptake by tumor cells;the nanogel releases drugs in acidic conditions;leading to cell death.White light irradiation further triggers BAO to produce substantial ROS;enhancing phototoxicity and synergistic chemo-PDT cancer therapy.Thus;P@BAO-DOX nanogels;as a smart nanoplatform;offer precise drug release and efficient ROS generation for imaging-guided chemo-PDT synergistic therapy;showing promise in advancing cancer treatment.
基金National Natural Science Foundation of China(62175198,62335018,12127805,62005309,61991452,U22A2092)Open Science Foundation of the Key Laboratory of Hepatobiliary Technology of Mengchao(2024ZDSY1001)Youth Innovation Promotion Association of the Chinese Academy of Sciences。
文摘Scattering media pose a significant barrier to non-invasive biomedical imaging,as conventional wavefront shaping methods rely on invasive guide stars or costly nonlinear modalities.Here,we introduce an improved approach that enables high-fidelity,non-invasive fluorescence imaging through scattering media by combining the linear fluorescence mechanism with efficient computational optimization.The method leverages a genetic algorithm guided by variance maximization to dynamically optimize speckle,non-invasively exciting an individual fluorescent bead by∼10-fold enhancement in target intensity ratio.This process generates a precise system point spread function(PSF),which drives a convex optimization-based deconvolution framework to reconstruct obscured targets.Remarkably,the technique eliminates the need for complex scanning systems,achieving rapid wide-field imaging with structural similarity(SSIM)indices exceeding 0.997(for beads).We demonstrate robust imaging of both discrete beads and continuous fibers behind scattering media,revealing resolution superior to that of conventional speckle cross-correlation methods.The method provides a pathway for non-invasively visualizing fluorescent objects behind scattering media.
基金supported by the National Natural Science Foundation of China(62175198,52273114,82103323,82003992,and U22A2092)the Fundamental Research Funds for the Central Universities(xtr062022002)+1 种基金Key Research and Development Program of Shaanxi Province under Grant No.2022ZDLSF04-09Beijing Natural Science Foundation(7222214).
文摘Systematic administration of small molecular drugs often suffered from the low efficacy and systemic toxicity in cancer therapy.In addition,application of single mode drug usually leads to unsatisfactory therapeutic out-comes.Currently,developing multimodal-drug combination strategy that acts on different pathways without increasing side effects remains great challenge.Here,we developed a hydrogel system that co-delivered glycolysis inhibitor apigenin and chemo-drug gemcitabine to realize combination strategy for combating can-cer with minimal systemic toxicity.We demonstrated that this system can not only eliminate tumor cells in situ,but also induce abscopal effect on various tumor models.These results showed that our study provided a safe and effective strategy for clinical cancer treatment.
