Sonodynamic therapy(SDT)has attracted great interest in the field of cancer therapy because of its non-invasiveness,deep penetration,spatiotemporal controllability.However,the sonodynamic effect is severely hindered b...Sonodynamic therapy(SDT)has attracted great interest in the field of cancer therapy because of its non-invasiveness,deep penetration,spatiotemporal controllability.However,the sonodynamic effect is severely hindered by hypoxia and a high glutathione(GSH)level in tumor microenvironment.In this work,a new type of nanohybrid sonosensitizer is designed,which incorporates several prominent advantages of organic,inorganic,natural sonosensitizers for imaging-guided SDT and ferroptosis induction.As an endogenous transporter,hemoglobin(Hb)has dual functions of oxygen and iron supplement.Apparently,Hb can transport iron to the tumor site for Fe-dependent ferroptosis,yet this oxygen carrier is able to enhance the sensitivity of tumor cells to oxygen-driven SDT.We innovatively hybridized Hb,sinoporphyrin sodium(DVDMS),titanium dioxide(TiO_(2))to prepare an integrated nano-oxygen carrier(designated as HDT)for multifarious cancer theranostics,which not only attained satisfactory sonosensitization of DVDMS/TiO_(2)but also achieved oxygen-boosted SDT and potent ferroptosis via Hb.Under ultrasound irradiation,the oxygenation of HDT markedly amplified the generation of reactive oxygen species(ROS)in hypoxic tumors,promoted the valence transition of Hb to accelerate Fenton reaction,led to ferroptosis.This strategy virtually eradicated tumors in situ and exhibited immunoregulatory potential for augmenting anti-tumor effects in vivo and in vitro through ROS formation,O_(2)self-supplement,GSH depletion,lipid peroxidation.Collectively,HDT demonstrated excellent dual-modal imaging performance,providing a valuable platform for photoacoustic/fluorescence-guided SDT and ferroptosis induction in tumor cells.展开更多
基金the Fundamental Research Funds for the Central Universities(No.GK202105004).
文摘Sonodynamic therapy(SDT)has attracted great interest in the field of cancer therapy because of its non-invasiveness,deep penetration,spatiotemporal controllability.However,the sonodynamic effect is severely hindered by hypoxia and a high glutathione(GSH)level in tumor microenvironment.In this work,a new type of nanohybrid sonosensitizer is designed,which incorporates several prominent advantages of organic,inorganic,natural sonosensitizers for imaging-guided SDT and ferroptosis induction.As an endogenous transporter,hemoglobin(Hb)has dual functions of oxygen and iron supplement.Apparently,Hb can transport iron to the tumor site for Fe-dependent ferroptosis,yet this oxygen carrier is able to enhance the sensitivity of tumor cells to oxygen-driven SDT.We innovatively hybridized Hb,sinoporphyrin sodium(DVDMS),titanium dioxide(TiO_(2))to prepare an integrated nano-oxygen carrier(designated as HDT)for multifarious cancer theranostics,which not only attained satisfactory sonosensitization of DVDMS/TiO_(2)but also achieved oxygen-boosted SDT and potent ferroptosis via Hb.Under ultrasound irradiation,the oxygenation of HDT markedly amplified the generation of reactive oxygen species(ROS)in hypoxic tumors,promoted the valence transition of Hb to accelerate Fenton reaction,led to ferroptosis.This strategy virtually eradicated tumors in situ and exhibited immunoregulatory potential for augmenting anti-tumor effects in vivo and in vitro through ROS formation,O_(2)self-supplement,GSH depletion,lipid peroxidation.Collectively,HDT demonstrated excellent dual-modal imaging performance,providing a valuable platform for photoacoustic/fluorescence-guided SDT and ferroptosis induction in tumor cells.
