A NIR-II responsive AuNRs@SiO₂–RB@MnO₂nanotheranostic has been successfully fabricated for photoacoustic and multimodal imaging-guided chemodynamic/photothermal synergistic therapies for tumors.

The high level of glutathione (GSH) in tumor cells can consume reactive oxygen species (ROS), seriously affecting the efficacy of chemodynamic therapy (CDT). Although it took a great deal of effort, developing a tumor-specific CDT that efficiently depletes GSH remains a formidable challenge. Herein, we propose a pH-responsive nanocatalyst containing the active molecule norcantharidin (NCTD) and Cu²⁺ for dual GSH depletion, achieving efficient GSH depletion. Due to the weakly acidic tumor microenvironment (TME), the catalyst releases NCTD and Cu²⁺ in a pH-responsive manner for the synergistic therapy of chemotherapy (CT) and CDT. Both components consume GSH and subsequently produce ROS, reducing the antioxidant capacity of cancer cells while increasing oxidative stress. This disrupts cellular redox homeostasis, leading to mitochondrial dysfunction and inducing tumor cell apoptosis. This work not only develops nanomaterials with dual GSH depletion capabilities for high-efficiency CDT but also achieves synergistic CT and CDT tumor therapy with the addition of NCTD, an active ingredient of traditional Chinese medicine.

Single tumor treatment method usually has some defects, which makes it difficult to achieve good therapeutic effect. The ingenious combination of multiple tumor treatment methods on a single nanoplatform to achieve multifunctional treatment can effectively improve the efficiency of treatment. The targeted modification of nanomaterials can augment the precision of nanotherapeutic drugs in tumor treatment. Herein, a multifunctional nanoplatform (CeO₂@CuS@PDA-FA) based on cerium dioxide nanoparticles engineered with copper sulfide (CeO₂@CuS) has been constructed for synergistic photothermal therapy (PTT) and chemodynamic therapy (CDT). The CeO₂@CuS were coated using polydopamine (PDA), and the modification of PDA surface by folic acid, in order to achieve the targeted effect for tumors. The localized hyperthermia induced by PTT can further improve the CDT efficiency of the nanoplatform, leading to a PTT/CDT synergistic effect. The nanoplatform possessed the capability of cancer cell-targeted and achieved better therapeutic efficacy in vitro. This work provided a new strategy for combined multifunctional theranostic platform and shows strong potential in practical applications.