2D-PROTACs with augmented protein degradation for super-resolution photothermal optical coherence tomography guided momentary multimodal therapy

•TaTe2 nanosheets with photothermal and photodynamic effect were discovered.•Super-resolution photothermal optical coherence chromatography imaging of tumor.•Nanoscale proteolysis-targeting chimeras were constructed with high biosafety.•Efficient protein degradation based on proteasome system.•Momentary multimodal antitumor in vivo and in vitro. Proteolytic targeting chimeras (PROTACs) are a strategy for protein degradation through proteasome degradation pathway, which has great potential in nano therapy. However, its degradation efficiency of target protein is low, which could not achieve the expected effect, leading to the failure of this tumor treatment. Herein, Two-dimensional (2D) nanosystems (2D-PROTACs: T-ARV) constructed from tantalum telluride (TaTe2) nanosheets loaded with PROTACs (ARV-825) in order to increase the contact probability between the target protein and E3 ligase and enhance the protein degradation performance. It can realize the efficient degradation of Bromodomain Containing 4 (BRD4) and C-MYC, so as to enhance the photothermal and photodynamic therapy of tumors. Importantly, as a photothermal optical coherence tomography (PT-OCT) contrast agent, T-ARV is able to provide micron-resolution three-dimensional images of tumor tissue, guided multimodal tumor therapy. Therefore, the construction of therapeutic strategies for 2D-PROTACs enables effectively improve the degradation efficiency of protacs to target proteins and enhance the therapeutic effect of nano preparations on tumors.