Encapsulation of Irinotecan in nanoporous porphyrin-based COF: An efficient drug delivery system for colorectal and breast cancer treatment

Irinotecan (IRI) is a water-soluble camptothecin derivative used to treat various types of cancers. However, its severe side effects and poor structural stability under physiological conditions have driven researchers to explore nanoparticle-based delivery systems to improve its efficiency and safety. Covalent organic frameworks (COFs) have gained significant attention among the latest advanced nanomaterials, due to their porosity, tunable structure, and excellent biocompatibility. . Here, we synthesized a porphyrin-based COF using a facile solvothermal method in an autoclave. The synthesized COF exhibited both micro and meso-porosity according to the BET analysis. After that, the drug loading capacity of the COF for IRI encapsulation was evaluated in the aqueous medium under different formulation conditions. The drug loading capacity was calculated at 23%, according to UV-vis spectroscopy and TGA analyses. Moreover, the IRI-loaded nanoparticle exhibited sustained drug release of 50% over approximately 60 hours at pH=5.4. The kinetic release study revealed that the release of IRI from COF@IRI followed the Korsmeyer−Peppas model with the Fickian mechanism. Furthermore, the cytotoxicity of the COF on normal human cells was evaluated and found to be biocompatible. Besides, the cytotoxicity assays of free IRI, COF, and COF@IRI were examined against human breast (MDA-MB-231) and colorectal (SW480) cancer cell lines. At the 40µM concentration, free IRI and COF@IRI showed similar effects in inhibiting cancer cell proliferation, with COF@IRI reducing the viability of colorectal and breast cancer cells to 67% and 63%, respectively. This study underscores the potential application of nanoporous COFs as promising carriers for IRI drug delivery.