Nitric Oxide Prodrug Delivery and Release Monitoring Based on a Galactose-Modified Multifunctional Nanoprobe.

Abstract

Nitric oxide (NO)-based cancer therapy has attracted much attention in recent years owing to its broad effects on cancer. Low concentrations of NO stimulate cancer cell progression, while its higher levels induce cell apoptosis, and thus, it has motivated the development of probes for in situ NO release monitoring. In this work, a galactose-modified benzothiadiazole-based fluorescent probe (GalNONP/C) was synthesized as both a NO-responsive nanoprobe and NO prodrug carrier. The probe exhibited far-red emission in the range from 550 to 800 nm, and the response showed acidity preference. The galactose on the probe enabled selective targeting of hepatocellular carcinoma (HCC) cells by binding to the asialoglycoprotein receptor (ASGPR) on the cell surface. The probe also delivered low-molecular weight NO prodrug JS-K into cells and monitored the real-time release of the generated NO. Furthermore, in vivo NO imaging with tumor targeting was demonstrated in HCC orthotopic transplantation nude mice and liver sections. Compared with the control experiment using a probe without NO prodrug loading, higher fluorescence response of NO was detected in the cell (3.0 times) and liver slices of the HCC tumor model (2.7 times). This strategy may pave the way to develop nanoprobes for in situ NO monitoring and therapy evaluation in NO-related cancer therapy.