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
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
The discovery of aggregation induced enmission(AIE)effect provides opportunities for the rapid development of fuorescence imaging-guided photodynamic therapy(PDT).In this work,a boron dipyrromethene(BODIPY)-based phot...The discovery of aggregation induced enmission(AIE)effect provides opportunities for the rapid development of fuorescence imaging-guided photodynamic therapy(PDT).In this work,a boron dipyrromethene(BODIPY)-based photosensitizer(ET-BDP-O)with AIE characteristics was developed,in which the two linear arms of BODIPY group were linked with triphenylamine to form an electron Donor-Acceptor-Donor(D-A-D)architecture while side chain was equipped with triethylene glycol group.ET-BDP-O was able to directly self-assemble into nanoparticles(NPs)without supplement of any other matrices or stabilizers due to its amphiphilic property.The as-prepared ET-BDP-O NPs had an excellent colloid stability with the size of 125 nm.Benefiting from the AIE property,ET-BDP-O NPs could generate strong fluorescence and reactive oxygen species under light-emitting diode light rradiation(60mW/cm^(2)).After inter-nalized in cancer cells,ET-BDP-O NPs were able to emit bright red fuorescence signal for bioimaging.In addition,the cell viability assay demonstrated that the ET-BDP-O NPs exhibited excellent photocytotoxicity against cancer cells,while negligible cytotoicity under dark envi-ronment.Thus,ET-BDP-O NPs might be regarded as a promising photosensitizer for fluores-cence imaging-guided PDT in future.展开更多
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.
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 Natural Science Foundation of China(Grant No.81871483)the Medical Innovation Project of Fujian Province(Grant No.2021CXA030).
文摘The discovery of aggregation induced enmission(AIE)effect provides opportunities for the rapid development of fuorescence imaging-guided photodynamic therapy(PDT).In this work,a boron dipyrromethene(BODIPY)-based photosensitizer(ET-BDP-O)with AIE characteristics was developed,in which the two linear arms of BODIPY group were linked with triphenylamine to form an electron Donor-Acceptor-Donor(D-A-D)architecture while side chain was equipped with triethylene glycol group.ET-BDP-O was able to directly self-assemble into nanoparticles(NPs)without supplement of any other matrices or stabilizers due to its amphiphilic property.The as-prepared ET-BDP-O NPs had an excellent colloid stability with the size of 125 nm.Benefiting from the AIE property,ET-BDP-O NPs could generate strong fluorescence and reactive oxygen species under light-emitting diode light rradiation(60mW/cm^(2)).After inter-nalized in cancer cells,ET-BDP-O NPs were able to emit bright red fuorescence signal for bioimaging.In addition,the cell viability assay demonstrated that the ET-BDP-O NPs exhibited excellent photocytotoxicity against cancer cells,while negligible cytotoicity under dark envi-ronment.Thus,ET-BDP-O NPs might be regarded as a promising photosensitizer for fluores-cence imaging-guided PDT in future.