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

Abstract

Traditional antitumor chemotherapy faces great challenges, such as multidrug 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.

Tumor Hypoxia Heterogeneity Affects Radiotherapy: Inverse-Percolation Shell-Model Monte Carlo Simulations

“…The understanding of such a mass distribution, density gradient, or connectivity network may have important implications for understanding the tumor biology and for its medical treatment. Notably, both therapy and imaging are often affected by tumor penetration difficulty, either by the drug or by the imaging contrast agent [ 2 ]. As an example, treatment by chemotherapy may be optimal only at the tumor periphery, because the progress of the drug into the tumor center may be hampered by the TME’s acidity.…”

Synthesis of Prussian Blue Nanoparticles and Their Antibacterial, Antiinflammation and Antitumor Applications

“…The recently developed NO-based gas treatment has been shown to lower multidrug resistance (MDR) and enhance absorption into tumor tissue. Fu et al have innovatively doped sodium nitroprusside (SNP) into HPB nanoparticles as a precursor, which can produce NO and be used for drug delivery (NO-PB) [ 96 ]. The results demonstrated that the release rate of DOX NO-PB was faster in acidic conditions than in neutral pH conditions.…”

Optical Microscopy Systems for the Detection of Unlabeled Nanoparticles

“…Also aiming at breast cancer therapy, Fu et al prepared doxorubicin (DOX)-loaded mesoporous Prussian blue NPs doped with the nitric oxide-producing prodrug sodium nitroprusside (NO-PB). 123 The authors showed that the release of encapsulated DOX was pH-dependent and that the particles produced NO molecules in cells, accumulated in tumor tissue, and could be imaged by PAM.…”