Boron neutron capture therapy(BNCT)is a binary radiotherapeutic modality based on the nuclear capture and fission reactions that occur when the stable isotope,boron-10,is irradiated with neutrons to produce high energ...Boron neutron capture therapy(BNCT)is a binary radiotherapeutic modality based on the nuclear capture and fission reactions that occur when the stable isotope,boron-10,is irradiated with neutrons to produce high energy alpha particles.This review will focus on tumor-targeting boron delivery agents that are an essential component of this binary system.Two low molecular weight boron-containing drugs currently are being used clinically,boronopheny-lalanine(BPA)and sodium borocaptate(BSH).Although they are far from being ideal,their therapeutic efficacy has been demonstrated in patients with high grade gliomas,recurrent tumors of the head and neck region,and a much smaller number with cutaneous and extra-cutaneous melanomas.Because of their limitations,great effort has been expended over the past 40 years to develop new boron delivery agents that have more favorable biodistribution and uptake for clinical use.These include boron-containing porphyrins,amino acids,polyamines,nucleosides,peptides,monoclonal antibodies,liposomes,nanoparticles of various types,boron cluster compounds and co-polymers.Cur-rently,however,none of these have reached the stage where there is enough convincing data to warrant clinical biodistribution studies.Therefore,at present the best way to further improve the clinical efficacy of BNCT would be to optimize the dosing paradigms and delivery of BPA and BSH,either alone or in combination,with the hope that future research will identify new and better boron delivery agents for clinical use.展开更多
Endo/lysosomal escape and gene release are two critical bottlenecks in gene delivery.Herein,a novel photo-controllable metal-organic frameworks(MOFs)nanoswitch is rationally designed for enhancing small interfering RN...Endo/lysosomal escape and gene release are two critical bottlenecks in gene delivery.Herein,a novel photo-controllable metal-organic frameworks(MOFs)nanoswitch is rationally designed for enhancing small interfering RNA(siRNA)delivery.One single laser triggers the“off-to-on”switching of MOFs nanocomplexes,inducing significant siRNA release accompanied by rapid MOFs dissociation into protonatable 2-methylimidazalo and osmotic rupturing Zn2+ions,which cooperatively contribute to remarkable endo/lysosomal rupture(∼90%).The simultaneous endo/lysosomal rupture and release enable a high spatio-temporal control on RNA interference for effective cancer therapy.Notably,the“off-to-on”switching also activates fluorescence recovery for real-time monitoring siRNA delivery.The nanoswitch could easily be extended to deliver other therapeutic agents(e.g.,DNA,protein,anticancer drug)for overcoming endo/lysosomal entrapment.展开更多
文摘Boron neutron capture therapy(BNCT)is a binary radiotherapeutic modality based on the nuclear capture and fission reactions that occur when the stable isotope,boron-10,is irradiated with neutrons to produce high energy alpha particles.This review will focus on tumor-targeting boron delivery agents that are an essential component of this binary system.Two low molecular weight boron-containing drugs currently are being used clinically,boronopheny-lalanine(BPA)and sodium borocaptate(BSH).Although they are far from being ideal,their therapeutic efficacy has been demonstrated in patients with high grade gliomas,recurrent tumors of the head and neck region,and a much smaller number with cutaneous and extra-cutaneous melanomas.Because of their limitations,great effort has been expended over the past 40 years to develop new boron delivery agents that have more favorable biodistribution and uptake for clinical use.These include boron-containing porphyrins,amino acids,polyamines,nucleosides,peptides,monoclonal antibodies,liposomes,nanoparticles of various types,boron cluster compounds and co-polymers.Cur-rently,however,none of these have reached the stage where there is enough convincing data to warrant clinical biodistribution studies.Therefore,at present the best way to further improve the clinical efficacy of BNCT would be to optimize the dosing paradigms and delivery of BPA and BSH,either alone or in combination,with the hope that future research will identify new and better boron delivery agents for clinical use.
基金supported by the Major State Basic Research Development Program of China(No.2017YFA0205201)the National Natural Science Foundation of China(Nos.81925019,81422023,U1705281,and U1505221)+1 种基金the Fundamental Research Funds for the Central Universities(No.20720190088)the Program for New Century Excellent Talents in University,China(No.NCET-13-0502).
文摘Endo/lysosomal escape and gene release are two critical bottlenecks in gene delivery.Herein,a novel photo-controllable metal-organic frameworks(MOFs)nanoswitch is rationally designed for enhancing small interfering RNA(siRNA)delivery.One single laser triggers the“off-to-on”switching of MOFs nanocomplexes,inducing significant siRNA release accompanied by rapid MOFs dissociation into protonatable 2-methylimidazalo and osmotic rupturing Zn2+ions,which cooperatively contribute to remarkable endo/lysosomal rupture(∼90%).The simultaneous endo/lysosomal rupture and release enable a high spatio-temporal control on RNA interference for effective cancer therapy.Notably,the“off-to-on”switching also activates fluorescence recovery for real-time monitoring siRNA delivery.The nanoswitch could easily be extended to deliver other therapeutic agents(e.g.,DNA,protein,anticancer drug)for overcoming endo/lysosomal entrapment.
