Small interfering RNA (siRNA)-mediated gene silencing is a promising therapeutic approach. Herein, we report the ambient synthesis of a positively charged iminium-linked covalent organic framework by a three-component one-pot reaction. Through anion exchange and siRNA adsorption, the resulting multifunctional siRNA@ABMBP-COF, which possesses both the HK2 inhibitor 3-bromopyruvate and SLC7A11 siRNA, exhibits powerful synergistic antitumor activity against fibrosarcoma via the ferroptosis and apoptosis pathways.
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