A puerarin-functionalized FeS2/Ti3C2 MXene nanoplatform for synergistic antitumor and osteogenic effects

Osteosarcoma (OS) is the most common bone tumor in adolescents, and effective treatment requires both tumor eradication and bone regeneration. Multifunctional nanotherapeutics that concurrently ablate tumors and promote bone repair are desirable. Here, we present a nanoplatform, Puerarin@FeS 2 /Ti 3 C 2 (P@F/T), designed for synergistic photothermal therapy, chemodynamic therapy, and osteogenic support. Ti 3 C 2 MXene acts as a photothermal agent under second near-infrared (NIR-II, 1064 nm) irradiation, while FeS 2 nanoparticles anchored on Ti 3 C 2 serve as peroxidase-mimicking Fenton catalysts. The FeS 2 /Ti 3 C 2 nanosheets are PEGylated via a dithiodiglycolic acid linker and loaded with puerarin, yielding P@F/T. In the acidic, H 2 O 2 -rich OS microenvironment, FeS 2 catalyzes H 2 O 2 into hydroxyl radicals via a Fenton-like reaction. Concurrently, NIR-II irradiation of Ti 3 C 2 produces localized hyperthermia. This combined photothermal and oxidative stress synergistically damages tumor cells, overcoming heat tolerance and antioxidant defenses. Simultaneously, the reductive intracellular environment cleaves the disulfide linker, triggering on-demand puerarin release. Released puerarin mitigates oxidative stress and promotes proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells. Overall, P@F/T integrates photothermal and chemodynamic tumor ablation with osteogenic therapy to treat OS while repairing bone defects.