GMBP1-conjugated manganese oxide nanoplates for in vivo monitoring of gastric cancer MDR using magnetic resonance imaging

Abstract

Multidrug resistance (MDR) is a huge challenge for gastric cancer chemotherapy. Therefore, MDR accurate monitoring is of great significance for the treatment of gastric cancer. GMBP1, an extracellular internalization peptide, can target MDR gastric cancer cells through specific binding to GRP78, which is an MDR-related protein that is overexpressed in gastric cancer cells. Herein, we constructed GMBP1 conjugated Mn₃O₄ nanoplates (Mn₃O₄@PEG-GMBP1 NPs) for in vivo monitoring of MDR gastric cancer through magnetic resonance imaging (MRI). The generated Mn₃O₄@PEG-GMBP1 NPs had a size of about 11 nm and exhibited a good colloidal stability in PBS and in 10% FBS medium. Serial in vivo MRI studies in mice demonstrated that the magnetic resonance signal intensity, at the tumor site, reached a peak at 3 h after tail vein injection of Mn₃O₄@PEG-GMBP1 NPs. The specific targeting ability of MDR gastric cancer cells (SGC7901/ADR) by Mn₃O₄@PEG-GMBP1 NPs was authenticated in vitro, in vivo and by immunofluorescence analysis experiments. The systematic safety evaluation indicated that the toxicity of Mn₃O₄@PEG-GMBP1 NPs in mice was negligible. Therefore, the GMBP1 conjugated Mn₃O₄ nanoplates can be clinically used for accurate imaging and monitoring of MDR gastric cancer.