Publication
SMA-BmobaSNO: an intelligent photoresponsive nitric oxide releasing polymer for drug nanoencapsulation and targeted delivery
Publisher:
IOP Publishing
Date:
15-02-2022
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 1/2 16 d) and metabolic ( t 1/2 32 h) decomposition, but rapidly brakes down under photoactivation (2700 W m −2 , halogen source) to release NO ( t 1/2 25 min). Photoresponsive NO release from SMA-BmobaSNO was confirmed in a cardiovascular preparation, where irradiation resulted in a 12-fold decrease in vasorelaxation EC 50 (from 5.2 μ M 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.