Tumor Reoxygenation and Blood Perfusion Enhanced Photodynamic Therapy using Ultrathin Graphdiyne Oxide Nanosheets

Both diffusion-limited and perfusion-limited hypoxia are associated with tumor progression, metastasis, and the resistance to therapeutic modalities. A strategy that can efficiently overcome both types of hypoxia to enhance the efficacy of cancer treatment has not been reported yet. Here, it is shown that by using biomimetic ultrathin graphdiyne oxide (GDYO) nanosheets, both types of hypoxia can be simultaneously addressed toward an ideal photodynamic therapy (PDT). The GDYO nanosheets, which are oxidized and exfoliated from graphdiyne (GDY), are able to efficiently catalyze water oxidation to release O₂ and generate singlet oxygen (¹O₂) using near-infrared irradiation. Meanwhile, GDYO nanosheets also exhibit excellent light-to-heat conversion performance with a photothermal conversion efficiency of 60.8%. Thus, after the GDYO nanosheets are coated with iRGD peptide-modified red blood membrane (i-RBM) to achieve tumor targeting, the biomimetic GDYO@i-RBM nanosheets can simultaneously enhance tumor reoxygenation and blood perfusion for PDT. This study provides new insights into utilizing novel water-splitting materials to relieve both diffusion- and perfusion-limited hypoxia for the development of a novel therapeutic platform.