Engineering Hybrid Sonodynamic Nanocarriers With Reduced Skin Phototoxicity

The rapid development of nanotechnology has promoted the emergence of various new treatment methods for effective treatment of cancer,such as photodynamic therapy,photothermal therapy and sonodynamic therapy.Among them,photodynamic therapy has the disadvantages of low tissue penetration and skin phototoxicity,which inhibits its treatment efficiency.Compared with traditional photodynamic therapy,sonodynamic therapy has obvious advantages and is a promising non-invasive tumor treatment method.As for various current trigger sources(such as laser,electric field,magnetic field,and radiation),ultrasound is non-invasive,convenient to use,and can penetrate tissues more efficiently than light.Sonodynamic therapy is suitable for the treatment of tumors embedded in internal organs;photodynamic therapy is difficult to deal with these tumors.In addition,most organic sonosensitizers are also photosensitizers,and hence there is problem of phototoxicity post therapy.The aim of this work was to synthesis a disulfide-bearing imidazole ligand to coordinate with zinc for producing glutathione(GSH)-and ultrasound-responsive metal organic framework(MOF)nanocarrier.The sonosensitizer titanium dioxide(TiO₂)was loaded in MOF to reduce phototoxicity.TiO₂can be activated by ultrasound to generate reactive oxygen species(ROS).Disulfide bonds in the MOF nanocarrier can deplete GSH,and the exhaustion of GSH can indirectly cause ferroptosis.The TiO₂ loading was determined to be 50.6±0.7%(w/w)with the aid of inductively coupled plasma mass(ICP-MS).Dynamic light scattering(DLS)and elemental mapping demonstrated that the nanocarriers contained the corresponding elements with an appropriate size distribution.The nanocarriers induced a significant cytotoxicity to 4T1 cells post ultrasound treatment.It has been demonstrated that imidazole can consume singlet oxygen to reduce phototoxicity.In summary,this current work reported a hybrid sonodynamic nanocarrier with a reduced phototoxicity.