Facile synthesis of Au NCs@POMA-Fe-FA nanoregulators with precise-targeted/NIR-laser-triggered/tumor microenvironment-responsive abilities for enhanced photothermal /photodynamic/chemodynamic therapy with photothermal imaging guidence

For overcoming the insurmountable obstacles of the multimodal combined therapy (MCT) in anti-cancer, tumor microenvironment regulation is considered an effective method. Hence, a TME adjustable, precise-targeted and near-infrared (NIR)-laser-responsive Au nanoclusters (NCs)@poly-o-mercaptoaniline (POMA)-Fe nanoregulators (NRGs) grafting with folic acid (FA) was designed and successfully fabricated by a simple redox with coordination method. The obtained Au NCs@POMA-Fe-FA NRGs could achieve the excellent TME regulation ability via the following avenues: the Fe 3+ ions are released by the acidic TME from the POMA-Fe-FA shell to transform the hydrogen peroxide (H 2 O 2 ) into O 2 for overcoming the hypoxia of TME. Further, the massive Fe 3+ ions are reduced by the excessive glutathione (GSH) in TME into Fe 2+ ions, which further react with H 2 O 2 to produce the hydroxyl radical (·OH) by Fenton reaction, realizing the chemodynamic therapy (CDT) to tumor. Moreover, the Au NC cores and the POMA-Fe-FA shell endow the nanoregulators with outstanding photodynamic and photothermal abilities triggered by NIR laser respectively. In addition, the consumption of GSH enhances the photodynamic therapy (PDT) and CDT synergistically. More importantly, the FA-induced targeting and NIR guided photothermal imaging grant the obtained nanoregulators outstanding selectivity for the precise tumor treatment and minimized side effect. The in vivo experimental results displayed that the tumor inhibition of the prepared Au NCs@POMA-Fe-FA NRGs could reach as high as about 84%. Obviously, the synthesized Au NCs@POMA-Fe-FA NRGs pave a new path for the design and preparation of novel multi-mode therapy for cancer with regulatory effects to TME.