Abstract
In this study, we synthesized manganese dioxide nanoparticles (MnO2 NPs) stabilized with biocompatible polymers (polyvinylpyrrolidone and polyacrylic acid) and analyzed their effect on non-small cell lung cancer (NSCLC) cells with or without gefitinib resistance in vitro. MnO2 NPs showed glutathione (GSH)-responsive dissolution and subsequent enhancement in magnetic resonance (MR) imaging. Of note, treatment with MnO2 NPs induced significant cytotoxic effects on NSCLC cells, and additional dose-dependent therapeutic effects were obtained upon X-ray irradiation. Normal cells treated with MnO2 NPs were viable at the tested concentrations. In addition, increased therapeutic efficacy could be achieved when the cells were treated with MnO2 NPs in hypoxic conditions. Therefore, we conclude that the use of MnO2 NPs in MR imaging and combination radiotherapy may be an efficient strategy for the imaging and therapy of NSCLC.
Highlights
The incidence of lung cancer has shown a consistent increase from to 2015
MnO2 NPs were synthesized by reducing potassium permanganate (KMnO4) to manganese dioxide (MnO2) in the presence of biocompatible polymers (i.e., PVP and PAA)
These results suggest that the dissolution of MnO2 NPs inside cancer cells could function as the Magnetic Resonance Imaging (MRI) contrast agent for both
Summary
The incidence of lung cancer has shown a consistent increase from to 2015. In 2015, despite elaborate efforts to detect cancers at early stages, the incidence of 2005 tracheal, bronchus, and lung cancers was 2 million (95% UI) and was the leading causes of cancer-related deaths worldwide, accounting for 1.7 million deaths (Fitzmaurice et al, 2017). Studies have shown that 40–80% of NSCLC patients overexpress epidermal growth factor receptor (EGFR), which plays an important role in growth, survival, and chemotherapy resistance (Herbst and Shin, 2002). Recent clinical trials have shown that EGFRtyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib and erlotinib represent the best first-line treatment options for patients with EGFR mutations. Most patients with EGFR mutations who were treated with EGFR-TKIs acquired resistance within 9–14 months (Morgillo et al, 2016). The development of effective therapeutic agents and methodologies to selectively treat NSCLC is an urgent, unmet clinical need
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