International Journal of Nanomedicine (Nov 2023)

A Novel pH-Responsive Iron Oxide Core-Shell Magnetic Mesoporous Silica Nanoparticle (M-MSN) System Encapsulating Doxorubicin (DOX) and Glucose Oxidase (Gox) for Pancreatic Cancer Treatment

  • Qi G,
  • Shi G,
  • Wang S,
  • Hu H,
  • Zhang Z,
  • Yin Q,
  • Li Z,
  • Hao L

Journal volume & issue
Vol. Volume 18
pp. 7133 – 7147

Abstract

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Guiqiang Qi,1 Guangyue Shi,1 Shengchao Wang,1 Haifeng Hu,2 Zhichen Zhang,1 Qiangqiang Yin,1 Zhongtao Li,1 Liguo Hao1,3 1Department of Molecular Imaging, School of Medical Technology, Qiqihar Medical University, Qiqihar, Heilongjiang, 161006, People’s Republic of China; 2Medical Imaging Center, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, 161000, People’s Republic of China; 3Department of Molecular Imaging, The First Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, 161041, People’s Republic of ChinaCorrespondence: Liguo Hao, Email [email protected]: This study developed a pancreatic cancer targeted drug delivery system that responds to changes in acidity. The system was based on iron oxide core-shell magnetic mesoporous silica nanoparticles (M-MSNs) to treat pancreatic cancer through combined chemotherapy and starvation therapy.Methods: Glucose oxidase (Gox) was coupled to the cancer cell surface to reduce glucose availability for cancer cells, exacerbating the heterogeneity of the tumor microenvironment. Reduced pH accelerated the depolymerization of pH-sensitive polydopamine (PDA), thereby controlling the spatial distribution of Gox and release of doxorubicin (DOX) within tumor cells.Results: Characterization results showed the successful synthesis of DG@M-MSN-PDA-PEG-FA (DG@NPs) with a diameter of 66.02 ± 3.6 nm. In vitro data indicated DG@NPs were highly effective and stable with good cellular uptake shown by confocal laser scanning microscopy (CLSM). DG@NPs exhibited high cytotoxicity and induced apoptosis. Additionally, in vivo experiments confirmed DG@NPs effectively inhibited tumor growth in nude mice with good biosafety. The combination of starvation therapy and chemotherapy facilitated drug release, suggesting DG@NPs as a novel drug delivery system for pancreatic cancer treatment.Conclusion: This study successfully constructed a doxorubicin release system responsive to acidity changes for targeted delivery in pancreatic cancer, providing a new strategy for combination therapy.Keywords: mesoporous silica nanoparticle, drug delivery, multitherapy modality, magnetic resonance imaging, glucose oxidase

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