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

Area of Science:

• Biomedical Engineering
• Chemical Biology
• Cancer Research

Background:

• Nitric oxide (NO) plays a dual role in cancer, stimulating growth at low concentrations and inducing apoptosis at high concentrations.
• Effective cancer therapy requires precise monitoring of NO levels and targeted delivery.
• Development of responsive probes is crucial for in situ NO release assessment in cancer treatment.

Purpose of the Study:

• To synthesize a galactose-modified benzothiadiazole-based fluorescent probe (GalNONP/C) for NO-responsive nanoprobe and NO prodrug carrier functions.
• To enable selective targeting of hepatocellular carcinoma (HCC) cells via galactose-ASGPR interaction.
• To monitor real-time NO release and evaluate NO-based cancer therapy in vitro and in vivo.

Main Methods:

• Synthesis of a galactose-modified benzothiadiazole-based fluorescent probe (GalNONP/C).
• Utilizing the probe for selective targeting of HCC cells through ASGPR binding.
• Loading the probe with NO prodrug JS-K for in situ NO generation and monitoring.
• Performing in vivo NO imaging in HCC orthotopic transplantation nude mice.

Main Results:

• The synthesized probe exhibited far-red emission (550-800 nm) with an acidity preference.
• Galactose modification enabled selective targeting and uptake by HCC cells.
• The probe successfully delivered JS-K and monitored real-time NO release.
• Significantly higher fluorescence response of NO was observed in targeted HCC cells (3.0x) and tumor tissues (2.7x) compared to controls.

Conclusions:

• The developed GalNONP/C probe serves as an effective NO-responsive nanoprobe and prodrug carrier for targeted HCC therapy.
• This strategy facilitates in situ NO monitoring and therapy evaluation in NO-related cancer treatments.
• The approach holds promise for advancing nanomedicine in cancer diagnostics and therapeutics.