International Journal of Nanomedicine (Jul 2019)

Hyaluronic acid-modified mesoporous silica-coated superparamagnetic Fe3O4 nanoparticles for targeted drug delivery

  • Fang Z,
  • Li X,
  • Xu Z,
  • Du F,
  • Wang W,
  • Shi R,
  • Gao D

Journal volume & issue
Vol. Volume 14
pp. 5785 – 5797

Abstract

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Zhengzou Fang,1 Xinyuan Li,2 Zeyan Xu,3 Fengyi Du,3 Wendi Wang,1 Ruihua Shi,4 Daqing Gao11Department of Pathogenic Microbiology and Immunology, Southeast University School of Medicine, Nanjing 210009, People’s Republic of China; 2Department of Clinical Laboratory, Huai’an Hospital Affiliated to Xuzhou Medical College and Huai’an Second Hospital, Huai’an, Jiangsu, People’s Republic of China; 3Department of Gastroenterology, Jiangsu University, School of Medicine, Zhenjiang 212013, People’s Republic of China; 4Department of Gastroenterology, Affiliated Zhongda Hospital, Southeast University, Nanjing 210009, People’s Republic of ChinaIntroduction: The targeted delivery of anti-cancer drugs to tumor tissue has been recognized as a promising strategy to increase their therapeutic efficacy and reduce side effects. Mesoporous silica-coated superparamagnetic Fe3O4 nanoparticles (NH2-MSNs), a kind of nanocarrier, can passively enter tumor tissues to enhance the permeability and retention of drugs. However, NH2-MSNs do not specifically bind to cancer cells. This drawback encouraged us to develop a more efficient nanocarrier for cancer therapy.Methods: Herein, we describe the development of an effective nanocarrier based on NH2-MSNs, which were modified with hyaluronic acid on their surface (HA-MSNs) and loaded with doxorubicin (DOX). We have successfully fabricated uniform spherical HA-MSNs nanocarriers. The targeting ability of this delivery system was evaluated through specific uptake by cells and IVIS imaging.Results: DOX-HA-MSNs nanocarriers displayed more dramatic cytotoxic activity against 4T1 breast cancer cells compared to GES-1 gastric mucosa cells. In vivo results revealed that once DOX-HA-MSNs nanocarriers are exposed to an external magnetic field, they could be rapidly attracted to the magnet and effectively cross the cytoplasmic membrane via CD44 receptor-mediated transcytosis. This allows them to access the cancer cell cytoplasm and release DOX based on changes in the physiological environment. Both in vitro and in vivo results demonstrated that the HA-MSNs nanocarriers provided better therapeutic efficacy.Conclusion: The HA-MSNs nanocarriers represent an effective new paradigm to treat cancers due to active targeting to the tumor cells. Moreover, the specific uptake by the tumor effectively protects normal tissues to reduce off-target side effects. The reported findings support further investigation of HA-MSNs for cancer therapy.Keywords: target-delivery, HA-MSNs, nanocarrier, receptor-mediated, cancer therapy

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