Encapsulation of tDodSNO generates a photoactivated nitric oxide releasing nanoparticle for localized control of vasodilation and vascular hyperpermeability

• Published in: Free radical biology & medicine Vol. 130; pp. 297 - 305
• Main Authors: Alimoradi, Houman, Barzegar-Fallah, Anita, Sammut, Ivan A., Greish, Khaled, Giles, Gregory I.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2019
• Subjects: Animals; Aorta - cytology; Aorta - drug effects; Capillary Permeability - drug effects; Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - metabolism; Cardiovascular Diseases - pathology; Controlled release; Drug; Drug Delivery Systems; Drug Liberation; Humans; Hyperpermeability; Macromolecule; Maleic Anhydrides - chemistry; Maleic Anhydrides - pharmacology; Nanoparticles - chemistry; Nitric oxide; Nitric Oxide - metabolism; Nitroprusside - pharmacology; Photoactivation; Polymers - chemistry; Polymers - pharmacology; Rats; S-Nitroso-N-Acetylpenicillamine - pharmacology; S-nitrosothiol; S-Nitrosothiols - chemistry; S-Nitrosothiols - pharmacology; Solubility - drug effects; Vasodilation; Vasodilation - drug effects; Water - chemistry; NO; NP; RT; Hyperpermeability; EBD; ddH2O; GSNO; sGC; Vasodilation; BSA; SNP; SNT; EC50; HPLC; Controlled release; Drug; Photoactivation; SMA; KH buffer; tDodSNO; SNAP; PE; Macromolecule; Nitric oxide; KH-I; S-nitrosothiol
• ISSN: 0891-5849; 1873-4596; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2018.10.433

We report the synthesis and characterization of a photoactive nitric oxide (NO) releasing nanoparticle (NP) by encapsulation of the NO donor tert-dodecane S-nitrosothiol (tDodSNO) into a co-polymer of styrene and maleic anhydride (SMA) to afford SMA-tDodSNO. Encapsulation did not affect tDodSNO's stability or NO release profile, but imparted water solubility and protection from degradation reactions with glutathione. Under photoactivation the NP acted as a potent NO donor, with photoactivation acting as a switch to induce localized vasodilation in aortic rings (EC50* 660 nM at 2700 W/m2) and cause vascular hyperpermeability in mesenteric beds (8-fold increase in dye uptake at 1 µM SMA-tDodSNO with 460 W/m2 photoactivation). The NP was markedly superior as a photoactive NO donor in comparison to the S-nitrosothiols GSNO and SNAP, which are commonly used in experimental studies, as well as sodium nitroprusside, a clinically used vasodilator. Future development of this NP may find wide ranging therapeutic applications for treating cardiovascular disease and other disorders related to NO signaling, as well as enhancing macromolecular drug delivery to target organs through selective hyperpermeability. Supporting information describing the biophysical characterization of SMA-tDodSNO is supplied in an accompanying Data in Brief article (Alimoradi et al., doi: 10.1016/j.dib.2018.10.149). [Display omitted] •Nanoparticle encapsulation of the nitric oxide donor tDodSNO generated a water soluble formulation SMA-tDodSNO.•Nanoparticle encapsulation did not change tDodSNO’s nitric oxide release profile.•Nanoparticle encapsulation protected tDodSNO from degradation by reduced glutathione.•Photoactivation of SMA-tDodSNO dynamically regulated vasodilation in aortic rings.•Photoactivation of SMA-tDodSNO caused vascular hyperpermeability in mesenteric beds.