SO₂ prodrug doped nanorattles with extra-high drug payload for "collusion inside and outside" photothermal/pH triggered - gas therapy.

Abstract

Recent years have witnessed the blooming of gas therapy nanoplatforms, which emerged as a promising area for cancer therapy. However, uncontrolled or inadequate generation of gas and unclear therapeutic mechanisms, which were still regarded as big challenges to apply gas therapy into clinical. Here in, a gas treatment based on sulfur dioxide (SO₂) prodrug doped nanorattles was explored, which could not only inhibit superficial tumor but also deep tumor. A Benzothiazole sulfinate (BTS, a water-soluble SO₂ prodrug) doped rattle-structured rough nanocapsule with high drug payload (~80%) composed of gold nanorods cores and polydopamine (PDA) shell (GNRs@PDA-BTS, GPBRs) has been prepared. Taking advantages of excellent photothermal conversion ability as well as acidic condition in the tumor sites, SO₂ gas release could be precisely controlled by both photothermal and pH, thus realizing "collusion inside" gas therapy and "outside" photothermal therapy. In addition, the cytotoxic SO₂ was found to induce cell apoptosis accompanied by the upregulation of intracellular reactive oxygen species (ROS) levels and modulation of apoptosis-relative proteins such as p53, bcl-2, Bax and caspase-3. Such photothermal/pH triggered SO₂ gas therapy may provide an effective strategy to stimulate further development of deep tumor therapy.