Blood lead(Pb(II))removal is very important but challenging.The main difficulty of blood Pb(II)removal currently lies in the fact that blood Pb(II)is mainly complexed with hemoglobin(Hb)inside the red blood cells(RBCs...Blood lead(Pb(II))removal is very important but challenging.The main difficulty of blood Pb(II)removal currently lies in the fact that blood Pb(II)is mainly complexed with hemoglobin(Hb)inside the red blood cells(RBCs).Traditional blood Pb(II)removers are mostly passive particles that do not have the motion ability,thus the efficiency of the contact between the adsorbent and the Pb(II)-contaminated Hb is relatively low.Herein,a kind of magnetic nanomotor adsorbent with movement ability under alternating magnetic field based on Fe3O4 nanoparticle modified with meso-2,3-dimercaptosuccinic acid(DMSA)was prepared and a blood Pb(II)removal strategy was further proposed.During the removal process,the nanomotor adsorbent can enter the RBCs,then the contact probability between the nanomotor adsorbent and the Pb(II)-contaminated Hb can be increased by the active movement of nanomotor.Through the strong coordination of functional groups in DMSA,the nanomotor adsorbent can adsorb Pb(II),and finally be separated from blood by permanent magnetic field.The in vivo extracorporeal blood circulation experiment verifies the ability of the adsorbent to remove blood Pb(II)in pig models,which may provide innovative ideas for blood heavy metal removal in the future.展开更多
Overexpression of glutathione(GSH) in tumor cells greatly inhibits the therapy effect of traditional ferroptosis inducers;thus,control of the GSH level is an important way to improve the efficacy of ferroptosis.Herein...Overexpression of glutathione(GSH) in tumor cells greatly inhibits the therapy effect of traditional ferroptosis inducers;thus,control of the GSH level is an important way to improve the efficacy of ferroptosis.Herein,a kind of nanomotor based on metal organic framework material NH_(2)-MIL-101 is constructed,in which polyethylene glycol(PEG) and glutathione hydrolase γ-glutamyltransferase(GGT) are asymmetrically modified to obtain mPEG@MIL-101@GGT nanomotors(PMG NMs).The nanomotor proposed in this article can be induced by overexpressing GSH in tumors to form chemotactic effects through the specific affinity between enzymes and substrates.Results indicate that the tail structure provided by PEG and the affinity between GGT and GSH can enable the stable chemotaxis behavior of nanomotors in a complex environment,thus enriching and penetrating deeply at the tumor site.In addition,after loading the ferroptosis inducer Erastin,the system shows a highly effective induction effect of tumor ferroptosis.Erastin in the system can effectively inhibit the synthesis of GSH,and PMG NMS can react with GSH through Fe^(3+)and GGT to promote GSH depletion.The produced Fe^(2+)can generate excessive reactive oxygen species through Fenton reaction,which further promotes the death of tumor cells.Meantime,the chemotaxis behavior of the nanomotors based on the endogenous biochemical reaction of GGT-catalyzed GSH hydrolysis can endow nanomotors with the enhanced delivery and penetration ability in tumors,thus collaboratively enhancing the ferroptosis effect.This strategy designed according to the physiological characteristics of tumors has good biosafety and treatment effect,providing new perspectives for micro/nanomotor and tumor treatment.展开更多
Reduction of endogenous hydrogen sulfide(H_(2)S)is considered to have an important impact on the progress of Parkinson’s disease(PD),thus exogenous H_(2)S supplementation is expected to become one of the key means to...Reduction of endogenous hydrogen sulfide(H_(2)S)is considered to have an important impact on the progress of Parkinson’s disease(PD),thus exogenous H_(2)S supplementation is expected to become one of the key means to treat PD.However,at present,it is difficult for H_(2)S donors to effectively penetrate the blood brain barrier(BBB),selectively release H_(2)S in brain,and effectively target the mitochondria of neuron cells.Herein,we report a kind of nanomotor-based H_(2)S donor,which is obtained by free radical polymerization reaction between L-cysteine derivative modified-polyethylene glycol(PEG-Cys)and 2-methacryloyloxyethyl phosphorylcholine(MPC).This kind of H_(2)S donor can not only effectively break through BBB,but also be specifically catalyzed by cystathionineβ-synthase(CBS)in neurons of PD site in brain and 3-mercaptopyruvate sulfurtransferase(3-MST)in mitochondria to produce H_(2)S,endowing it with chemotaxis/motion ability.Moreover,the unique chemotaxis effect of nanomotor can realize the purpose of precisely targeting brain and the mitochondria of damaged neuron cytopathic diseases.This kind of nanomotor-based H_(2)S donor is expected to enrich the current types of H_(2)S donors and provide new ideas for the treatment of PD.展开更多
Glioblastoma(GBM) is the most aggressive malignant brain tumor. Due to the infiltration and heterogeneity of GBM, the obstruction of the blood-brain barrier(BBB) and the unique immunosuppressive mechanism, it is hard ...Glioblastoma(GBM) is the most aggressive malignant brain tumor. Due to the infiltration and heterogeneity of GBM, the obstruction of the blood-brain barrier(BBB) and the unique immunosuppressive mechanism, it is hard to achieve significant effects of GBM treatment. Here, a kind of chemotactic nanomotor that loaded with glucose oxidase(GOx) and carboxylated cisplatin(Pt(IV)) prodrug on the L-arginine-derived polymer is proposed. The nanomotors are driven by catalysis of glucose decomposition and the positive chemotaxis towards the GBM microenvironment where inducible nitric oxide synthase and reactive oxygen species are highly expressed. This facilitates the BBB crossing and GBM targeting of the nanomotors. In addition, the released nitric oxide(NO) during propulsion as well as the loaded GOx and Pt(IV) can exert combined NO/starvation/chemotherapy. Meanwhile, it is able to induce and enhance the immune response through multiple pathways, thus better coping with the complexities of GBM treatment.展开更多
基金Social development project of Jiangsu Natural Science Foundation(No:BE2019744)Jiangsu Collaborative Innovation Center of Biomedical Functional Materials,National Natural Science Foundation of China(51641104,21603105)+1 种基金Natural Science Foundation of Jiangsu Province(BK20171115)the Priority Academic Program Development of Jiangsu Higher Education Institution.
文摘Blood lead(Pb(II))removal is very important but challenging.The main difficulty of blood Pb(II)removal currently lies in the fact that blood Pb(II)is mainly complexed with hemoglobin(Hb)inside the red blood cells(RBCs).Traditional blood Pb(II)removers are mostly passive particles that do not have the motion ability,thus the efficiency of the contact between the adsorbent and the Pb(II)-contaminated Hb is relatively low.Herein,a kind of magnetic nanomotor adsorbent with movement ability under alternating magnetic field based on Fe3O4 nanoparticle modified with meso-2,3-dimercaptosuccinic acid(DMSA)was prepared and a blood Pb(II)removal strategy was further proposed.During the removal process,the nanomotor adsorbent can enter the RBCs,then the contact probability between the nanomotor adsorbent and the Pb(II)-contaminated Hb can be increased by the active movement of nanomotor.Through the strong coordination of functional groups in DMSA,the nanomotor adsorbent can adsorb Pb(II),and finally be separated from blood by permanent magnetic field.The in vivo extracorporeal blood circulation experiment verifies the ability of the adsorbent to remove blood Pb(II)in pig models,which may provide innovative ideas for blood heavy metal removal in the future.
基金supported by the National Natural Science Foundation of China (22175096)the Social Development Project of Jiangsu Natural Science Foundation (BE2019744)+1 种基金the Collaborative Innovation Center of Biomedical Functional Materialsthe Priority Academic Program Development of Jiangsu Higher Education Institution。
文摘Overexpression of glutathione(GSH) in tumor cells greatly inhibits the therapy effect of traditional ferroptosis inducers;thus,control of the GSH level is an important way to improve the efficacy of ferroptosis.Herein,a kind of nanomotor based on metal organic framework material NH_(2)-MIL-101 is constructed,in which polyethylene glycol(PEG) and glutathione hydrolase γ-glutamyltransferase(GGT) are asymmetrically modified to obtain mPEG@MIL-101@GGT nanomotors(PMG NMs).The nanomotor proposed in this article can be induced by overexpressing GSH in tumors to form chemotactic effects through the specific affinity between enzymes and substrates.Results indicate that the tail structure provided by PEG and the affinity between GGT and GSH can enable the stable chemotaxis behavior of nanomotors in a complex environment,thus enriching and penetrating deeply at the tumor site.In addition,after loading the ferroptosis inducer Erastin,the system shows a highly effective induction effect of tumor ferroptosis.Erastin in the system can effectively inhibit the synthesis of GSH,and PMG NMS can react with GSH through Fe^(3+)and GGT to promote GSH depletion.The produced Fe^(2+)can generate excessive reactive oxygen species through Fenton reaction,which further promotes the death of tumor cells.Meantime,the chemotaxis behavior of the nanomotors based on the endogenous biochemical reaction of GGT-catalyzed GSH hydrolysis can endow nanomotors with the enhanced delivery and penetration ability in tumors,thus collaboratively enhancing the ferroptosis effect.This strategy designed according to the physiological characteristics of tumors has good biosafety and treatment effect,providing new perspectives for micro/nanomotor and tumor treatment.
基金supported by National Natural Science Foundation of China(No:22175096,No:22275095)Qinglan Project Foundation of Colleges and Universities of Jiangsu Province,Jiangsu Collaborative Innovation Center of Biomedical Functional Materials,Priority Academic Program Development of Jiangsu Higher Education Institution.
文摘Reduction of endogenous hydrogen sulfide(H_(2)S)is considered to have an important impact on the progress of Parkinson’s disease(PD),thus exogenous H_(2)S supplementation is expected to become one of the key means to treat PD.However,at present,it is difficult for H_(2)S donors to effectively penetrate the blood brain barrier(BBB),selectively release H_(2)S in brain,and effectively target the mitochondria of neuron cells.Herein,we report a kind of nanomotor-based H_(2)S donor,which is obtained by free radical polymerization reaction between L-cysteine derivative modified-polyethylene glycol(PEG-Cys)and 2-methacryloyloxyethyl phosphorylcholine(MPC).This kind of H_(2)S donor can not only effectively break through BBB,but also be specifically catalyzed by cystathionineβ-synthase(CBS)in neurons of PD site in brain and 3-mercaptopyruvate sulfurtransferase(3-MST)in mitochondria to produce H_(2)S,endowing it with chemotaxis/motion ability.Moreover,the unique chemotaxis effect of nanomotor can realize the purpose of precisely targeting brain and the mitochondria of damaged neuron cytopathic diseases.This kind of nanomotor-based H_(2)S donor is expected to enrich the current types of H_(2)S donors and provide new ideas for the treatment of PD.
基金supported by the National Natural Science Foundation of China(22175096,22275095)the Social Development Project of Jiangsu Natural Science Foundation(BE2019744)+3 种基金the Qinglan Project Foundation of Colleges and Universities of Jiangsu Provincethe Jiangsu Collaborative Innovation Center of Biomedical Functional Materialsthe Priority Academic Program Development of Jiangsu Higher Education Institutionthe Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX22_1545)。
文摘Glioblastoma(GBM) is the most aggressive malignant brain tumor. Due to the infiltration and heterogeneity of GBM, the obstruction of the blood-brain barrier(BBB) and the unique immunosuppressive mechanism, it is hard to achieve significant effects of GBM treatment. Here, a kind of chemotactic nanomotor that loaded with glucose oxidase(GOx) and carboxylated cisplatin(Pt(IV)) prodrug on the L-arginine-derived polymer is proposed. The nanomotors are driven by catalysis of glucose decomposition and the positive chemotaxis towards the GBM microenvironment where inducible nitric oxide synthase and reactive oxygen species are highly expressed. This facilitates the BBB crossing and GBM targeting of the nanomotors. In addition, the released nitric oxide(NO) during propulsion as well as the loaded GOx and Pt(IV) can exert combined NO/starvation/chemotherapy. Meanwhile, it is able to induce and enhance the immune response through multiple pathways, thus better coping with the complexities of GBM treatment.
