Graphdiyne-templated palladium-nanoparticle assembly as a robust oxygen generator to attenuate tumor hypoxia

Nanocatalysts have attracted many concerns in biomedical fields because their catalytic performance is robust and remains efficient even at a harsh condition compared to biological enzymes. However, the stability for both physical forms and the catalytic activity are the main challenges during biomedical applications. Here, we described a strategy to prepare a stable nanocatalyst that two-dimensional (2D) graphdiyne (GDY) serves as a template to immobilize catalytic palladium nanoparticles (PdNPs) on the GDY surface. In the presence of H2O2, the PdNPs/GDY composite functions as an oxygen generator to decompose H2O2 to produce molecular oxygen, which efficiently attenuates tumor hypoxia and delays tumor growth. According to X-ray absorption spectroscopy and computational simulation, we revealed that PdNPs mainly contribute to the decomposition of H2O2 into O2 companying with the variation in chemical forms of Pd in the presence of H2O2. Importantly, 2D GDY firmly anchors and disperses ultra-small PdNPs on the surface via Pd-C bonds to prevent the oxidation and aggregation of PdNPs that realizes sustainable and stable catalysis. This design endows the highly immobilized content of Pd on GDY, high catalytic activity and higher stability in catalytic reaction than commercial Pd/C and PdNPs/GO, accordingly. The PdNPs/GDY composite also exhibits as an effective and durable oxygen generator to decompose endogenous H2O2 and produces O2 inside solid tumors, attenuates tumor hypoxia, down-regulates HIF-1α expression and ultimately delays tumor growth in both human patient-derived squamous cell lung carcinoma xenograft model and 4T1 breast cancer xenografted mouse model. Moreover, in the combination with the chemotherapeutic agent, doxorubicin, PdNPs/GDY-based catalytic therapy achieved a significantly enhanced antitumor effect. Our findings demonstrate that the rational design of a nano-modulator for tumor hypoxia with long term stability is a promising way to enhance the outcome of tumor therapy.