The low objective response rates and severe side effects largely limit the clinical outcomes of immune checkpoint blockade(ICB)therapy.Here,a tumor“self-killing”therapy based on gene-guided OX40L anchoring to tumor ...The low objective response rates and severe side effects largely limit the clinical outcomes of immune checkpoint blockade(ICB)therapy.Here,a tumor“self-killing”therapy based on gene-guided OX40L anchoring to tumor cell membrane was reported to boost ICB therapy.We developed a highly efficient delivery system HA/PEI-KT(HKT)to co-deliver the OX40L plasmids and unmethylated CG-enriched oligodeoxynucleotide(CpG).On the one hand,CpG induced the expression of OX40 on T cells within tumors.On the other hand,OX40L plasmids achieved the OX40L anchoring on the tumor cell membrane to next promote T cells responses via OX40/OX40L axis.Such synergistic tumor“self-killing”strategy finally turned“cold”tumors to“hot”,to sensitize tumors to programmed cell death protein 1/programmed cell death ligand 1(PD-1/PD-L1)blockade therapy,and promoted an immune-mediated tumor regression in both B16F10 and 4T1 tumor models,with prevention of tumor recurrence and metastasis.To avoid the side effects,the gene-guided OX40L anchoring and PD-L1 silencing was proposed to replace the existing antibody therapy,which showed negligible toxicity in vivo.Our work provided a new possibility for tumor“self-killing”immunotherapy to treated various solid tumors.展开更多
Covalent organic framework(COF)materials have great development value in the biomedical field.However,the huge size and poor dispersion of COF materials severely limit their application.Here we successfully prepared C...Covalent organic framework(COF)materials have great development value in the biomedical field.However,the huge size and poor dispersion of COF materials severely limit their application.Here we successfully prepared COF nanoparticles with uniform size and good dispersion under the assistance of microwave.By adding some cationic polymers or small amine molecules,the dispersibility of COF could be further improved and its surface charge also increased.The prepared cationic COF nanoparticles(CLZU NPs)had excellent gene transfection ability and good biocompatibility.Designing low-toxic and highefficiency gene carrier is an important mission in the field of gene therapy.This COF-based gene vector provides a new direction for gene carrier design.展开更多
基金This work was financially supported by the National Key R&D Program of China(2021YFB3800900)National Natural Science Foundation of China(51925305,51873208,51833010,51803210,51973217)Jilin province science and technology development program(20200201075JC).
文摘The low objective response rates and severe side effects largely limit the clinical outcomes of immune checkpoint blockade(ICB)therapy.Here,a tumor“self-killing”therapy based on gene-guided OX40L anchoring to tumor cell membrane was reported to boost ICB therapy.We developed a highly efficient delivery system HA/PEI-KT(HKT)to co-deliver the OX40L plasmids and unmethylated CG-enriched oligodeoxynucleotide(CpG).On the one hand,CpG induced the expression of OX40 on T cells within tumors.On the other hand,OX40L plasmids achieved the OX40L anchoring on the tumor cell membrane to next promote T cells responses via OX40/OX40L axis.Such synergistic tumor“self-killing”strategy finally turned“cold”tumors to“hot”,to sensitize tumors to programmed cell death protein 1/programmed cell death ligand 1(PD-1/PD-L1)blockade therapy,and promoted an immune-mediated tumor regression in both B16F10 and 4T1 tumor models,with prevention of tumor recurrence and metastasis.To avoid the side effects,the gene-guided OX40L anchoring and PD-L1 silencing was proposed to replace the existing antibody therapy,which showed negligible toxicity in vivo.Our work provided a new possibility for tumor“self-killing”immunotherapy to treated various solid tumors.
基金financially supported by the National Natural Science Foundation of China (51390484, 21474104, 51403205, 51503200 and 51520105004)National program for support of Top-notch young professionalsJilin province science and technology development program (20160204032GX, 20180414027GH)
基金supported by the National Natural Science Foundation of China(51925305,51873208,51520105004,51833010,51803210,51803014)the National Science and Technology Major Projects for Major New Drugs Innovation and Development(2018ZX09711003-012)Jilin Province Science and Technology Development Program(20180414027GH)。
文摘Covalent organic framework(COF)materials have great development value in the biomedical field.However,the huge size and poor dispersion of COF materials severely limit their application.Here we successfully prepared COF nanoparticles with uniform size and good dispersion under the assistance of microwave.By adding some cationic polymers or small amine molecules,the dispersibility of COF could be further improved and its surface charge also increased.The prepared cationic COF nanoparticles(CLZU NPs)had excellent gene transfection ability and good biocompatibility.Designing low-toxic and highefficiency gene carrier is an important mission in the field of gene therapy.This COF-based gene vector provides a new direction for gene carrier design.
