Activatable Plasmonic Versatile Nanoplatform for Glutathione-Depletion Augmented Ferroptosis and NIR-II Photothermal Synergistic Therapy

Abstract

Ferroptosis-based therapy exhibits promising prospects for the treatment of malignant tumors. However, the practical therapeutic benefits of ferroptosis-based antitumor therapy are usually restricted by excess endogenous antioxidants and relatively sluggish ROS production kinetics. Here, an activatable plasmonic versatile nanoplatform (AuSi@ FePB) with glutathione (GSH)-depletion capacity is reported for synergistic ferroptosis therapy and second near-infrared window photothermal therapy (NIR-II PTT). The nanoplatform exhibits stability in physiological conditions, but in the tumor microenvironment, its Fe-PDA shell gradually disintegrates to increase intracellular ferrous supply for elevated ROS generation and GSH-depletion in response to overexpressed GSH, leading to amplified ferroptosis of tumor cells. The integration of NIR-II laser irradiation facilitates the generation of localized heat, which not only effectively triggers photothermal therapy but also significantly enhances the Fenton reaction, thereby promoting ferroptotic cell death in tumor cells. While the oxidative damage can also downregulate the heat repair effect, thereby facilitating the PTT efficacy. More importantly, such synergism not only results in the elimination of the primary tumor but also triggers a systemic antitumor immune response, facilitating the regression of nontreated distant tumors and impeding the occurrence of lung metastasis. The in vivo therapeutic mechanism was further verified by transcriptome sequencing, demonstrating that synergistic GSH-depletion augmented ferroptosis therapy and NIR-II PTT are an effective combination antitumor strategy. This study presents a promising perspective for cancer treatment based on ferroptosis and also sheds new light on novel therapeutic platforms for future cancer therapy.

Review of NIR-responsive ‘‘Smart’’ carriers for photothermal chemotherapy

“…Sun et al reported the development of the NIR-II activable nanoplatform termed AuSi@FePB, which was designed for synergistic ferroptosis therapy and photothermal therapy. 76 The fabrication of the AuSi@FePB nanoplatform involved coating a polydopamine shell coordinated with iron (Fe-PDA) on silica-encapsulated gold nanochains (AuNCs@SiO 2 ), with the GSH synthesis inhibitor l -BSO incorporated on the surface of Fe-PDA. NIR-II photoirradiation-induced local heating not only efficiently triggered photothermal therapy (PTT) but also notably amplified the Fenton reaction, resulting in the production of reactive oxygen species (ROS) and depletion of glutathione (GSH).…”

Advancing NIR-II Photothermal Antibacterial Capability of Polydopamine Nanoparticles through Iron-Doped Molybdenum Oxide Functionalization

“…In recent years, chemodynamic therapy (CDT) has emerged as a promising treatment modality. − Fenton/Fenton-like reactions facilitate the conversion of H 2 O 2 into hydroxyl radicals, employing Fe and other metals with distinct valence states. When combined with photothermal therapy (PTT), this synergistic approach not only utilizes thermal energy to eradicate bacteria but also accelerates the generation of free radicals, thereby exhibiting synergistic antibacterial effects. , …”