Enhanced Bax upregulating in mitochondria for deep tumor therapy based on SO₂ prodrug loaded Au-Ag hollow nanotriangles.

Abstract

Nowadays, limited deep tumor penetration and lower therapeutic effect are still the major obstacle in nanomedicines for cancer therapy. Here, we developed high-efficiency nanocomposites, SO₂ prodrug (BTS) loaded Au-Ag hollow nanotriangles (Au-Ag-BTS HTNs), which could not only synergistically upregulate Bax expression in mitochondria, but also be triggered by acidic tumor microenvironment to generate SO₂ for deep tumor therapy. Upon NIR laser irradiation, Au-Ag hollow nanotriangles (Au-Ag HTNs) produced plenty of heat for photothermal therapy (PTT), while the acidic condition in tumor cells induced on-demand SO₂ release from BTS for deep tumor therapy. More importantly, the combined therapy could simultaneously upregulate the expression of apoptosis factor Bax as well as downregulate Bcl-2 in mitochondria, which would induce an increase of Caspase-3 expression to accelerate the apoptosis of tumor cells, thereby achieving a win-win cooperation. The results indicated that enhanced deep tumor therapeutic effect based on Au-Ag-BTS HTNs was realized in vitro and in vivo. Such pH-triggered SO₂ therapy offered a novel strategy for responding tumor microenvironment and improving penetration and heterogeneity distribution of nanotherapeutics in tumor.