Nanoplaform based on ultra-small Au regulating phototoxicity and fluorescence off–on function of Ag2S for multi-modal diagnosis and treatment of tumor

Abstract

• Hydrophobic ultra-small (3 ∼ 5 nm) nano-Au particle (mAu) is synthesized. • ASAuDP probe greatly reduces the phototoxicity of Ag 2 S. • Ag 2 S in ASAuDP probe achieves off–on FL imaging at tumor site. • mAu has CT, PAI, PTT and SDT capabilities thus reducing the dosage of ASAuDP probe. • The synergistic effect of PTT and SDT presents better tumor killing ability. In this paper, a mixture of lecithin, polyethylene glycol monostearate, and polyethylene glycol phospholipid (DSPE-PEG 2000 ) is used to wrap hydrophobic nano silver sulfide (Ag 2 S) and 3 ∼ 5 nm ultra-small gold nanoparticle (mAu) to form ∼ 150 nm hydrophilic nanocomposite probe Ag 2 S/Au@DSPE-PEG 2000 (ASAuDP) with good stability and dispersion. The probe combines the functions of Ag 2 S and mAu, while mAu can significantly inhibit the fluorescence (FL) of Ag 2 S, thereby reducing the phototoxicity of probe when circulating in the body. When the ASAuDP probe is phagocytosed by tumor cell, Ag 2 S and mAu are separated due to the rupture of probe, thereby restoring the ability of FL imaging and ROS production. MTT test, blood analysis and organ pathology test prove that ASAuDP is a safe probe. In vitro and in vivo imaging experiments prove that the ASAuDP probe presents good FL, CT and photoacoustic imaging capabilities. In vitro and in vivo treatments prove that the ASAuDP probe has both photothermal and sonodynamic therapy abilities, and the synergy between them has the best therapeutic effect. Therefore, ASAuDP probe is a kind of integrated diagnostic and therapeutic probe with good safety, and it has a good application prospect in the treatment of tumor.