Magnetic covalent organic framework-based nanoadjuvant for multi-amplify sonodynamic antitumor therapy effect

Superior sonosensitizer and targeted delivery of sonosensitizer are critical factors in determining the effectiveness of sonodynamic therapy (SDT). We developed magnetic targeting covalent organic framework (COF) nanoparticles to act as sonosensitizer and nanoadjuvant to multi-amplify the SDT effect at tumor sites. First, coreshell Fe3O4 @COF nanoparticles with uniform size were prepared by "molecule exchange method" based on imine exchange reaction and further cationized, finally loaded with unmethylated cytosine-phosphate-guanine (CpG) adjuvant. The structural confinement of the porphyrin-based COF enhanced the sonodynamic performance, and the Fe3O4 endowed the COF with chemodynamic effect to enhance SDT effect. More importantly, the superparamagnetism of Fe3O4 could enable magnetic COF nanoparticles to actively target tumor sites, which further increased the treatment effect of SDT against simulated deep-seated tumors. Because of the presence of CpG adjuvant, this nanoplatform could be used as an in situ vaccine to achieve effective tumor immunotherapy to further amplify the treatment effect. This innovative method of preparing COF with core-shell structure and the enhanced SDT strategy effectively inhibited tumor growth and prevented tumor recurrence and metastasis, providing a new reference for clinical application.