Enhanced Oral NO Delivery through Bioinorganic Engineering of Acid-Sensitive Prodrug into a Transformer-like DNIC@MOF Microrod

Yong Huei Hong, Manmath Narwane, Lawrence Yu Min Liu, Yi Da Huang, Chieh Wei Chung, Yi Hong Chen, Bo Wen Liao, Yu Hsiang Chang, Cheng Ru Wu, Hsi Chien Huang, I. Jui Hsu, Ling Yun Cheng, Liang Yi Wu, Yu Lun Chueh, Yunching Chen, Chia Her Lin, Tsai Te Lu*

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

摘要

Nitric oxide (NO) is an endogenous gasotransmitter regulating alternative physiological processes in the cardiovascular system. To achieve translational application of NO, continued efforts are made on the development of orally active NO prodrugs for long-term treatment of chronic cardiovascular diseases. Herein, immobilization of NO-delivery [Fe2(μ-SCH2CH2COOH)2(NO)4] (DNIC-2) onto MIL-88B, a metal–organic framework (MOF) consisting of biocompatible Fe3+ and 1,4-benzenedicarboxylate (BDC), was performed to prepare a DNIC@MOF microrod for enhanced oral delivery of NO. In simulated gastric fluid, protonation of the BDC linker in DNIC@MOF initiates its transformation into a DNIC@tMOF microrod, which consisted of DNIC-2 well dispersed and confined within the BDC-based framework. Moreover, subsequent deprotonation of the BDC-based framework in DNIC@tMOF under simulated intestinal conditions promotes the release of DNIC-2 and NO. Of importance, this discovery of transformer-like DNIC@MOF provides a parallel insight into its stepwise transformation into DNIC@tMOF in the stomach followed by subsequent conversion into molecular DNIC-2 in the small intestine and release of NO in the bloodstream of mice. In comparison with acid-sensitive DNIC-2, oral administration of DNIC@MOF results in a 2.2-fold increase in the oral bioavailability of NO to 65.7% in mice and an effective reduction of systolic blood pressure (SBP) to a ΔSBP of 60.9 ± 4.7 mmHg in spontaneously hypertensive rats for 12 h.

原文英語
頁(從 - 到)3849-3863
頁數15
期刊ACS Applied Materials and Interfaces
14
發行號3
DOIs
出版狀態已發佈 - 2022 1月 26

ASJC Scopus subject areas

  • 材料科學(全部)

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