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Hong, Yong-Huei; Narwane, Manmath; Liu, Lawrence Yu-Min; Huang, Yi-Da; Chung, Chieh-Wei; Chen, Yi-Hong; Liao, Bo-Wen; Chang, Yu-Hsiang; Wu, Cheng-Ru; Huang, Hsi-Chien; Hsu, I-Jui; Cheng, Ling-Yun; Wu, Liang-Yi; Chueh, Yu-Lun; Chen, Yunching; Lin, Chia-Her; Lu, Tsai-Te
ACS applied materials & interfaces, 2022-Jan-26, 2022-01-26, 20220126, Letnik: 14, Številka: 3Journal Article
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 Fe (μ-SCH CH COOH) (NO) ( ) onto MIL-88B, a metal-organic framework (MOF) consisting of biocompatible Fe 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 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 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 in the small intestine and release of NO in the bloodstream of mice. In comparison with acid-sensitive , 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.
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