Metal-organic framework for biomimetic nitric oxide generation and anticancer drug delivery

The potential therapeutic implications of nitric oxide (NO) have drawn a great deal of interest for reversing multidrug resistance (MDR) in cancer; however, previous strategies utilized unstable or toxic NO donors often oxidized by the excessive addition of reactive oxygen species, leading to unexpe...

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Bibliographic Details
Published in:Biomaterials advances 2023-02, Vol.145, p.213268, Article 213268
Main Authors: Ji, Han Bi, Kim, Se-Na, Kim, Cho Rim, Min, Chang Hee, Han, Jae Hoon, Kim, Min Ji, Lee, Cheol, Choy, Young Bin
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Biomimetics
Irinotecan - therapeutic use
Metal-Organic Frameworks - therapeutic use
Mice
Mice, Nude
Neoplasms - drug therapy
Neoplasms - pathology
Nitric Oxide - therapeutic use
Nitric Oxide Donors - therapeutic use
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Summary:The potential therapeutic implications of nitric oxide (NO) have drawn a great deal of interest for reversing multidrug resistance (MDR) in cancer; however, previous strategies utilized unstable or toxic NO donors often oxidized by the excessive addition of reactive oxygen species, leading to unexpected side effects. Therefore, this study proposed a metal-organic framework (MOF), Porous coordination network (PCN)-223-Fe, to be loaded with a biocompatible NO donor, L-arginine (L-arg; i.e., PCN-223-Fe/L-arg). This specific MOF possesses a ligand of Fe-porphyrin, a biomimetic catalyst. Thus, with PCN-223-Fe/L-arg, L-arg was released in a sustained manner, which generated NO by a catalytic reaction between L-arg and Fe-porphyrin in PCN-223-Fe. Through this biomimetic process, PCN-223-Fe/L-arg could generate sufficient NO to reverse MDR at the expense of hydrogen peroxide already present and highly expressed in cancer environments. For treatment of MDR cancer, this study also proposed PCN-223-Fe loaded with an anticancer drug, irinotecan (CPT-11; i.e., PCN-223-Fe/CPT-11), to be formulated together with PCN-223-Fe/L-arg. Owing to the synergistic effect of reversed MDR by NO generation and sustained release of CPT-11, this combined formulation exhibited a higher anticancer effect on MDR cancer cells (MCF-7/ADR). When intratumorally injected in vivo, coadministration of PCN-223-Fe/L-arg and PCN-223-Fe/CPT-11 greatly suppressed tumor growth in nude mice bearing MDR tumors.
ISSN:2772-9508
2772-9508
DOI:10.1016/j.bioadv.2022.213268