SMA-BmobaSNO: an intelligent photoresponsive nitric oxide releasing polymer for drug nanoencapsulation and targeted delivery

Houman Alimoradi; Ansa Thomas; Daniel D B Lyth; Anita Barzegar-Fallah; Siddharth S Matikonda; Allan B Gamble; Gregory I Giles

doi:10.1088/1361-6528/ac4eb0

SMA-BmobaSNO: an intelligent photoresponsive nitric oxide releasing polymer for drug nanoencapsulation and targeted delivery

Nanotechnology. 2022 Feb 15;33(19). doi: 10.1088/1361-6528/ac4eb0.

Authors

Houman Alimoradi¹, Ansa Thomas¹, Daniel D B Lyth¹, Anita Barzegar-Fallah², Siddharth S Matikonda², Allan B Gamble², Gregory I Giles¹

Affiliations

¹ Department of Pharmacology and Toxicology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
² School of Pharmacy, University of Otago, Dunedin, New Zealand.

PMID: 35078165
DOI: 10.1088/1361-6528/ac4eb0

Abstract

Nitric oxide (NO) is an important biological signalling molecule that acts to vasodilate blood vessels and change the permeability of the blood vessel wall. Due to these cardiovascular actions, co-administering NO with a therapeutic could enhance drug uptake. However current NO donors are not suitable for targeted drug delivery as they systemically release NO. To overcome this limitation we report the development of a smart polymer, SMA-BmobaSNO, designed to release NO in response to a photostimulus. The polymer's NO releasing functionality is an S-nitrosothiol group that, at 10 mg ml^-1, is highly resistant to both thermal (t_1/216 d) and metabolic (t_1/232 h) decomposition, but rapidly brakes down under photoactivation (2700 W m^-2, halogen source) to release NO (t_1/225 min). Photoresponsive NO release from SMA-BmobaSNO was confirmed in a cardiovascular preparation, where irradiation resulted in a 12-fold decrease in vasorelaxation EC₅₀(from 5.2μM to 420 nM). To demonstrate the polymer's utility for drug delivery we then used SMA-BmobaSNO to fabricate a nanoparticle containing the probe Nile Red (NR). The resulting SMA-BmobaSNO-NR nanoparticle exhibited spherical morphology (180 nm diameter) and sustained NR release (≈20% over 5 d). Targeted delivery was characterised in an abdominal preparation, where photoactivation (450 W m^-2) caused localized increases in vasodilation and blood vessel permeability, resulting in a 3-fold increase in NR uptake into photoactivated tissue. Nanoparticles fabricated from SMA-BmobaSNO therefore display highly photoresponsive NO release and can apply the Trojan Horse paradigm by using endogenous NO signalling pathways to smuggle a therapeutic cargo into target tissue.

Keywords: drug delivery; hyperpermeability; nanoparticle; nitric oxide; photoactivation; polymer; vasodilation.