Boron neutron capture therapy(BNCT)is a novel binary therapy combining boron targeted drugs and neutron irradiation,which can selectively and effectively kill cancer cells at the cellular scale.Controlled release of b...Boron neutron capture therapy(BNCT)is a novel binary therapy combining boron targeted drugs and neutron irradiation,which can selectively and effectively kill cancer cells at the cellular scale.Controlled release of boron drug and its accumulation in tumor sites are the crux of BNCT.Here,we developed a^(10)B-boric acid(^(10)BA)-loaded nanofiber applying for BNCT by in situ administration.The nanofibers were obtained by electrospinning technique using polyethylene glycol/polylactide(PEO/PLA)block copolymers.By changing the ratio of hydrophilicity to hydrophobicity of the nanofibers,the controlled release and the effective accumulation of boron 10 isotope(^(10)B)were achieved in situ.The^(10)B content in tumor could reach to 2540μg/g,significantly exceeding the required level of 20–50μg/g for BNCT operation.Utilizing pertinent DNA damage experiments,direct evidence and quantified data of BNCT-induced DNA damage in tumor cells were obtained for the first time.Transcriptome sequencing was employed to predict the molecular mechanisms and potential signaling pathways of BNCT,providing theoretical basis for future combined therapies.The antitumor efficiency of BNCT was demonstrated by establishing mice model of subcutaneous tumor and tumor recurrence.The research presents a novel boron-loaded nanofiber mats for BNCT,which enables controlled drug release and holds significant potential in the treatment of unresectable or postoperative residual tumors.展开更多
Chemotherapeutic and radiation therapy have emerged as two most important treatment strategies to treat cancer in clinical practice;however,to improve anticancer efficacy,combination chemotherapy still remains challen...Chemotherapeutic and radiation therapy have emerged as two most important treatment strategies to treat cancer in clinical practice;however,to improve anticancer efficacy,combination chemotherapy still remains challenge.Dichloroacetate(DCA)could produce significant cytotoxic effects in certain tumor cells through its distinct mechanism.Radiation therapy with fast neutrons(FNT)has high relative biolgical effectiveness compared to other radiotherapeutics.Herein,we reported the combination chemotherapy with FNT for effective tumor growth inhibition with the assistance of a multilayered nanofiber loading DCA and DCA derivatives.We first synthesized a biodegradable polylysine to condense DCA with negative charge,or to conjugate DCA by condensing synthesis,to obtain Ion-DCA and Co-DCA,respectively.DCA,Ion-DCA or Co-DCA was then loaded into fibers to form multilayer drug-loaded mats.Upon adhesion on the surface of subcutaneous and orthotopic liver tumors,the multilayer drug-loaded mats realized a controllable release of DCA,which reversed the Warburg effect and inhibited cancer cell proliferation.Meantime,irradiation of fast neutrons could seriously damage DNA structure.Combination of the controllable release of DCA and FNT resulted in synergistic cell apoptosis in vitro,and the tumor inhibition in vivo.This study thus provides a new approach to integrate chemotherapy and FNT with the assistance of biocompatible nanofiber for synergistic tumor therapy.展开更多
基金supported by the National Natural Science Foundation of China(Nos.21975246,52103193,and 52273124)the Natural Science Foundation of Shenzhen Municipality(No.JCYJ20230807112801003)+2 种基金the Projects of Jilin Province Science and Technology Development Plan(No.20220101052JC)the Fundamental Research Funds for the Central Universities(No.2412023QD017)the Fundamental Research Funds for the Central Universities-Excellent Youth Team Program(No.2412023YQ001).
文摘Boron neutron capture therapy(BNCT)is a novel binary therapy combining boron targeted drugs and neutron irradiation,which can selectively and effectively kill cancer cells at the cellular scale.Controlled release of boron drug and its accumulation in tumor sites are the crux of BNCT.Here,we developed a^(10)B-boric acid(^(10)BA)-loaded nanofiber applying for BNCT by in situ administration.The nanofibers were obtained by electrospinning technique using polyethylene glycol/polylactide(PEO/PLA)block copolymers.By changing the ratio of hydrophilicity to hydrophobicity of the nanofibers,the controlled release and the effective accumulation of boron 10 isotope(^(10)B)were achieved in situ.The^(10)B content in tumor could reach to 2540μg/g,significantly exceeding the required level of 20–50μg/g for BNCT operation.Utilizing pertinent DNA damage experiments,direct evidence and quantified data of BNCT-induced DNA damage in tumor cells were obtained for the first time.Transcriptome sequencing was employed to predict the molecular mechanisms and potential signaling pathways of BNCT,providing theoretical basis for future combined therapies.The antitumor efficiency of BNCT was demonstrated by establishing mice model of subcutaneous tumor and tumor recurrence.The research presents a novel boron-loaded nanofiber mats for BNCT,which enables controlled drug release and holds significant potential in the treatment of unresectable or postoperative residual tumors.
基金This work was supported by the National Natural Science Foundation of China(Nos.51273194,21975246 and 51903233).
文摘Chemotherapeutic and radiation therapy have emerged as two most important treatment strategies to treat cancer in clinical practice;however,to improve anticancer efficacy,combination chemotherapy still remains challenge.Dichloroacetate(DCA)could produce significant cytotoxic effects in certain tumor cells through its distinct mechanism.Radiation therapy with fast neutrons(FNT)has high relative biolgical effectiveness compared to other radiotherapeutics.Herein,we reported the combination chemotherapy with FNT for effective tumor growth inhibition with the assistance of a multilayered nanofiber loading DCA and DCA derivatives.We first synthesized a biodegradable polylysine to condense DCA with negative charge,or to conjugate DCA by condensing synthesis,to obtain Ion-DCA and Co-DCA,respectively.DCA,Ion-DCA or Co-DCA was then loaded into fibers to form multilayer drug-loaded mats.Upon adhesion on the surface of subcutaneous and orthotopic liver tumors,the multilayer drug-loaded mats realized a controllable release of DCA,which reversed the Warburg effect and inhibited cancer cell proliferation.Meantime,irradiation of fast neutrons could seriously damage DNA structure.Combination of the controllable release of DCA and FNT resulted in synergistic cell apoptosis in vitro,and the tumor inhibition in vivo.This study thus provides a new approach to integrate chemotherapy and FNT with the assistance of biocompatible nanofiber for synergistic tumor therapy.
