Advanced Postsynthetic Modification of COF: Elevating Hydrophilicity for Efficient Doxorubicin Delivery

Parvin Asadi; Nazanin Mokhtari; Saeid Asghari; Hyeonji Rha; Ghadamali Khodarahmi; Hanieh Jalali; Amit Sharma; Mohammad Dinari; Jong Seung Kim

doi:10.1021/acsabm.5c00436

Advanced Postsynthetic Modification of COF: Elevating Hydrophilicity for Efficient Doxorubicin Delivery

Parvin Asadi^*
, Nazanin Mokhtari
, Saeid Asghari
, Hyeonji Rha
, Ghadamali Khodarahmi
, Hanieh Jalali
, Amit Sharma^*
, Mohammad Dinari^*
, Jong Seung Kim^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

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.

Original language	English
Pages (from-to)	4325-4336
Number of pages	12
Journal	ACS Applied Bio Materials
Volume	8
Issue number	5
DOIs	https://doi.org/10.1021/acsabm.5c00436
Publication status	Published - 2025 May 19

Bibliographical note

Publisher Copyright:
© 2025 American Chemical Society.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

covalent organic frameworks
cytotoxicity
doxorubicin
drug delivery systems
hydrophilicity

ASJC Scopus subject areas

Biomaterials
General Chemistry
Biomedical Engineering
Biochemistry, medical

Access to Document

10.1021/acsabm.5c00436

Cite this

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title = "Advanced Postsynthetic Modification of COF: Elevating Hydrophilicity for Efficient Doxorubicin Delivery",

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.",

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author = "Parvin Asadi and Nazanin Mokhtari and Saeid Asghari and Hyeonji Rha and Ghadamali Khodarahmi and Hanieh Jalali and Amit Sharma and Mohammad Dinari and Kim, \{Jong Seung\}",

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T2 - Elevating Hydrophilicity for Efficient Doxorubicin Delivery

AU - Asadi, Parvin

AU - Mokhtari, Nazanin

AU - Asghari, Saeid

AU - Rha, Hyeonji

AU - Khodarahmi, Ghadamali

AU - Jalali, Hanieh

AU - Sharma, Amit

AU - Dinari, Mohammad

AU - Kim, Jong Seung

PY - 2025/5/19

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N2 - 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.

AB - 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.

KW - covalent organic frameworks

KW - cytotoxicity

KW - doxorubicin

KW - drug delivery systems

KW - hydrophilicity

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ER -

Advanced Postsynthetic Modification of COF: Elevating Hydrophilicity for Efficient Doxorubicin Delivery

Abstract

Bibliographical note

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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