Multifunctional MnO2 nanosheet based DNA tetrahedron- photosensitizer nanoplatform for gene-photodynamic modulation

Photodynamic therapy (PDT) holds great promise for treating various types of cancer. However, its clinical advancement is hindered by the intrinsic hypoxic tumor microenvironment, which reduces PDT efficacy, and safety concerns related to the biological specificity of photosensitizers. Here we constructed a MnO 2 nanosheet based DNA tetrahedron-photosensitizer (TMPyP4) nanoplatform (TPM), which integration with tumor targeting (aptamer), gene drugs (DNAzyme) and photosensitizer agents for enhanced PDT. Once the TPM entered cancer cells through aptamer targeting, the MnO 2 nanosheet reacts with endogenous acidic and H 2 O 2 to generate Mn 2+ and oxygen (O 2 ), thereby alleviating the tumor hypoxic. Subsequently, TMPyP4 further converts the generated O 2 into singlet oxygen ( 1 O 2 ) under near-infrared light, enhancing PDT efficacy both in vitro and in vivo. Specifically, the generated Mn 2+ activates the DNAzyme and accelerate tumor target mRNA cleavage, resulting in effective PDT-gene synergistic therapy for tumors. This work offers novel perspectives on advancing precise and highly effective gene-PDT systems.