Light‐Enhanced Tandem‐Responsive Nano Delivery Platform for Amplified Anti‐tumor Efficiency

Designing nanomedicines with low toxicity, high targeting, excellent therapeutic effects, and precise release is always the major challenges in clinical cancer treatment. Here, we report a light‐enhanced tandem‐responsive nano delivery platform COF‐B@X‐03 for amplified anti‐tumor efficiency. Biotin‐loaded COF‐B@X‐03 could precisely target tumor cells, and the azo and hydrazone bonds in it would be depolymerized by the overexpressed azoreductase and acidic microenvironment in hypoxic tumors. In vitro experimental results indicate mitochondrial and endoplasmic reticulum stress caused by COF‐B@X‐03 under light is the direct cause of tumor cell death. In vivo experimental data prove COF‐B@X‐03 achieves low oxygen dependent phototherapy, and the maintenance of intratumoral hypoxia provides the possibility for the continuous degradation of COF‐B@X‐03 to generate more reactive oxygen species for tumor photodynamic therapy by released X‐03. In the end, COF‐B@X‐03 phototherapy group achieves higher tumor inhibition rate than X‐03 phototherapy group, which is 81.37%. Meanwhile, COF‐B@X‐03 significantly eliminates the risk of tumor metastasis. In summary, the construction of this tandem‐responsive nano delivery platform provides a new direction for achieving efficient removal of solid tumors in clinical practice.