Biodegradable tetrasulfide bonds incorporated mesoporous polyamidoamine nanoplatform for enhancing antitumor efficiency via photothermal enhanced GSH depletion

Owing to the heat resistance of heat shock proteins that trigger cellular antioxidants like glutathione (GSH), it is challenging to simultaneously inhibit the spread and metastasis of tumor nodules and prevent tumor recurrence using conventional photothermal therapy (PTT). In this research, for incorporation of PTT and GSH depletion, we utilized mesoporous polydopamine nanospheres doped with GSH-responsive tetrasulfide bonds (referred to as gMPDA) for the synergistic suppression of lung cancer cells. By incorporating Arg-Gly-Asp (RGD) peptides onto the surface (forming gMPDA-RGD), the stability and tumor-targeting specificity of this biodegradable nanoplatforms were markedly improved. In vitro studies testified that these innovative nanotherapeutics displayed an impressive photothermal conversion efficiency (η = 52.33 %) and efficient consumption of intracellular GSH, leading to the collapse of the PDA based nanoframe. Notably, the disruption of redox balance post-808 nm laser irradiation led to effective PTT and reactive oxygen species (ROS) production. Importantly, gMPDA-RGD manifested a strong tumor-targeting ability in lung tumor-bearing Balb/C mice under fluorescent imaging. The synergistic treatments led to complete elimination of tumor cells when exposed to 808 nm laser irradiation. This study underscored the potential of gMPDA-RGD as a potent nanomedicine for the synergistic therapy of PTT and GSH depletion in clinical malignant tumor.