Template-Free Self-Assembly of Hollow Microtubular Covalent Organic Frameworks for Oral Delivery of Insulin

Covalent organic frameworks (COFs) have demonstrated versatile application potential since their discovery. Although the structure of COFs is orderly arranged, the synthesis of controllable macrostructures still faces challenges. Herein, we report, to our knowledge, the first template-free self-assembled COF-18 Å hollow microtubule (MT-COF-18 Å) structure and its use for insulin delivery that exhibits high loading capacity, gastroresistance, and glucose-responsive properties. The hollow MT-COF-18 Å was achieved by a template-free method benefiting from the mixed solvents of mesitylene and dioxane. The formation mechanism and morphology changes with insulin loading and release were observed. In Caco-2 cells, the transferrin-coated system demonstrated enhanced insulin cellular uptake and transcellular transport, which indicated great potential for oral applications. Additionally, the composites presented sustained glycemic control and effective insulin blood concentrations without noticeable toxicity in diabetic rats. This work shows that hollow microtubular COFs hold great promise in loading and delivery of biomolecules.