International Journal of Nanomedicine (Oct 2020)

pH-Responsive Fluorescence Enhanced Nanogel for Targeted Delivery of AUR and CDDP Against Breast Cancer

  • Cao Z,
  • Li W,
  • Liu R,
  • Li C,
  • Song Y,
  • Liu G,
  • Chen Y,
  • Lu C,
  • Lu A,
  • Liu Y

Journal volume & issue
Vol. Volume 15
pp. 8369 – 8382

Abstract

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Zhiwen Cao,1 Wen Li,1 Rui Liu,1 Chenxi Li,1 Yurong Song,1 Guangzhi Liu,1 Youwen Chen,1 Cheng Lu,2 Aiping Lu,3 Yuanyan Liu1 1School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 2Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, People’s Republic of China; 3School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hongkong, People’s Republic of ChinaCorrespondence: Yuanyan Liu; Aiping Lu Tel +86 10 84738658Email [email protected]; [email protected]: Auraptene (AUR), a natural bioactive prenyloxy coumarin, is a highly pleiotropic molecule that can bind to the MT1 receptor and can effectively reduce the proliferation and migration of breast cancer cells. Cisplatin (CDDP), as the first synthetic platinum-based anticancer drug, is widely used in the clinic due to its definite mechanism and therapeutic effect on diverse tumors. However, both of AUR and CDDP exhibit some disadvantages when used alone, including poor solubility, low bioavailability, lack of selectivity and systemic toxicity when they are used singly.Methods: Therefore, the biodegradable materials hyaluronic acid (HA) and β-cyclodextrin derivative (mono-(6-amino-mono-6-deoxy)-β-CD, CD) were employed as carriers to load AUR and CDDP to form nanogel ([email protected]) capable of dual-targeted delivery and synergistic therapy for breast cancer and cell imaging.Results: With the help of the CDDP-crosslinked CD-loaded structure, the newly synthesized nanogel exhibited excellent physiological stability and fluorescence effects. The release of AUR and CDDP was affected by the pH value, which was beneficial to the selective release in the tumor microenvironment. Cell experiments in vitro demonstrated that the nanogel could be selectively internalized by MCF-7 cells and exhibited low cytotoxicity to HK-2 cells. Antitumor experiments in vivo showed that the nanogel have better antitumor effects and lower systemic toxicity.Conclusion: Based on these, the nanogel loaded with AUR and CDDP have the potential for targeted delivery against breast cancer.Keywords: auraptene, cisplatin, cell imaging, tumor targeting, pH-responsive

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