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Advanced Postsynthetic Modification of Cof: Elevating Hydrophilicity for Efficient Doxorubicin Delivery Publisher Pubmed



P Asadi PARVIN ; N Mokhtari NAZANIN ; S Asghari SAEID ; H Rha HYEONJI ; Ga Khodarahmi Ghadam ALI ; H Jalali HANIEH ; Ak Sharma Amit K ; M Dinari MOHAMMAD ; Js Kim Jong SEUNG
Authors

Source: ACS Applied Bio Materials Published:2025


Abstract

Covalent organic frameworks (COFs) show great potential as drug delivery systems (DDSs) due to their customizable structures, stability, and capacity for pore surface functionalization. However, their natural hydrophobicity limits their dispersion in water, posing challenges for biological applications. We address this issue by initially reducing a COF (Az-COF) to an amine-linked form (Az-AL-COF) and subsequently sulfonating it to obtain Az-AL-SO3H-COF, a water-dispersible derivative. Water contact angle (WCA) analysis confirmed increased hydrophilicity across the series of 84.5, 61.2, and 54.7° for Az-COF, Az-AL-COF, and Az-AL-SO3H-COF, respectively. Using doxorubicin (Dox) as a model drug, the modified COFs exhibited pH-sensitive drug release, with greater release at acidic pH (5.6) compared to neutral pH (7.4). Cytotoxicity assays revealed that Az-AL-SO3H-COF was biocompatible with normal cells (MCF-10) while effectively suppressing the growth of cancer cells (MDA-MB-231). The Dox-loaded sulfonated COF (Dox@Az-AL-SO3H-COF) showed selective cytotoxicity against cancer cells, highlighting its potential as a pH-responsive, biocompatible DDS for cancer treatment. © 2025 Elsevier B.V., All rights reserved.
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