Cyanine-Assisted Exfoliation of Covalent Organic Frameworks in Nanocomposites for Highly Efficient Chemo-Photothermal Tumor Therapy.

Abstract

Covalent organic frameworks (COFs) have received considerable interest because of their advanced applications. However, their low dispersibility and aqueous stability are intractable issues limiting their biomedical application. To address the issue, water-dispersible nanocomposites (COF@IR783) produced through the assembly of cyanines and COFs are proposed and prepared. Therefore, a strategy of "killing three birds with one stone" is developed. First, the nanocomposites exhibit superior dispersibility and aqueous stability compared to COFs. The nanocomposites have a nanosized morphology and negative charges, which are in favor of improving the blood circulation and enhanced permeability and retention-mediated tumor-targeting delivery therapy for in vivo application. Second, the nanocomposites have enhanced photothermal therapy (PTT) ability in the near-infrared region compared to cyanines. The nanocomposites also have a photoacoustic imaging ability, which can guide the antitumor therapy in vivo. Lastly, the nanocomposites can be further used as drug-delivery carriers for loading the anticancer cis-aconityl-doxorubicin (CAD) prodrug. In comparison with individual PTT or chemotherapy, the combination of PTT and chemotherapy achieved with COF@IR783@CAD synergistically induced the death of cancer cells in vitro, and an intravenous injection of COF@IR783@CAD in mice resulted in significant tumor ablation. This work indicates that the dispersibility and aqueous stability of COFs can be appropriately overcome through a rational design and can further expand the biomedical applications of COFs.