Synergistic Therapy Using Doxorubicin-Loading and Nitric Oxide-Generating Hollow Prussian Blue Nanoparticles with Photoacoustic Imaging Potential Against Breast Cancer

INTRODUCTION: Traditional antitumor chemotherapy faces great challenges, such as multi-drug resistance (MDR) and poor penetration into tumor tissues. The newly emerging nitric oxide (NO)-based gas therapy has been recognized to reduce MDR and has improved permeation into tumor tissue. METHODS: In this study, NO-generating prodrug sodium nitroprusside (SNP) was doped to hollow mesoporous Prussian blue (PB) nanoparticles to fabricate NO-generating nanoparticles (NO-PB), which was further loaded with doxorubicin (DOX). RESULTS: DOX loaded NO-PB (DOX-NO-PB) was released quicker at pH 6 compared with neutral pH, suggesting NO-PB may facilitate the release of loaded drug in acidic tumor tissue. The capacity of NO production by NO-PB was measured, and the results showed the presence of NO in the culture medium from 4T1 cells incubated with NO-PB and inside the cells. NP-PB could be detected by photoacoustic imaging (PAI) in tumor tissue in 4T1 tumor bearing mice, suggesting this nanoparticle may serve as contrast agent for the noninvasive diagnosis of tumor tissues. NO-PB suppressed the growth of tissues in 4T1 tumor bearing mice. DOX-NO-PB showed more potent anti-tumor effects in 4T1 cells and tumor bearing mice compared with free DOX and NO-PB alone, indicating that the combination of DOX and NO-PB exhibited synergistic effects on tumor suppression. CONCLUSION: This study provides a novel nanocarrier for gas therapy with additional PAI imaging capacity. This nanocarrier can be utilized for combination therapy of NO and chemotherapeutics which may serve as theranostic agents.