Etching Bulk Covalent Organic Frameworks into Nanoparticles of Uniform and Controllable Size by the Molecular Exchange Etching Method for Sonodynamic and Immune Combination Antitumor Therapy

Abstract To improve the therapeutic effect of sonodynamic therapy (SDT), more effective and stable sonosensitizers and therapeutic strategies are still required. A covalent organic framework (COF) sonosensitizer is developed by using a new nanoscale COF preparation strategy. This strategy uses molecular etching based on the imine exchange reaction to etch the bulk COF into nanoparticles and has universal applicability to imine‐bond‐based COF. The regular COF structure can prevent the loss of sonodynamic performance caused by the aggregation of porphyrin molecules and improve the chemical stability of the porphyrin unit. In addition, the coordination of Fe3+ to COF endows the nanoparticle with chemodynamic therapy performance and glutathione consumption ability. The combination of enhanced SDT and α‐PD‐L1 antibody achieves a good antitumor effect. The innovative nanoscale COF sonosensitizer preparation strategy provides a new avenue for clinical antitumor therapy.