Folic Acid-Functionalized Metal-Organic Framework Nanoparticles as Drug Carriers Improved Bufalin Antitumor Activity Against Breast Cancer

Hairong Zeng; Chao Xia; Bei Zhao; Mengmeng Zhu; HaoYue Zhang; Die Zhang; Xin Rui; Huili Li; Yi Yuan

doi:10.3389/fphar.2021.747992

Folic Acid-Functionalized Metal-Organic Framework Nanoparticles as Drug Carriers Improved Bufalin Antitumor Activity Against Breast Cancer

Front Pharmacol. 2022 Jan 18:12:747992. doi: 10.3389/fphar.2021.747992. eCollection 2021.

Authors

Hairong Zeng^{1

2

3}, Chao Xia⁴, Bei Zhao², Mengmeng Zhu⁴, HaoYue Zhang⁵, Die Zhang¹, Xin Rui⁶, Huili Li⁴, Yi Yuan¹

Affiliations

¹ Department of Pharmacy, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
³ Interventional Cancer Institute of Chinese Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
⁴ Engineering Research Center for Nanophotonics and Advanced Instrument, Ministry of Education, School of Physics and Electronic Science, East China Normal University, Shanghai, China.
⁵ Colorectal Disease Center of Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.
⁶ Baoshan Branch, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Abstract

Bufalin (Buf), an active ingredient of the traditional Chinese medicine Chansu, is known to have anticancer effects for breast cancer. However, its poor solubility, high toxicity, and extensive side effects limit its use. Metal-organic frameworks (MOFs) are a class of promising drug delivery systems known for their high porosity. Here, we designed and constructed pH-sensitive and redox-responsive folic acid-modified MOFs as drug carriers of Buf (FA-MOF/Buf). Moreover, the anticancer activity of nanomedicines was also explored in vitro and in vivo. Compared to free Buf, the FA-MOF/Buf nanoparticles demonstrated improved water solubility and stability, higher intracellular uptake, and enhanced cytotoxicity in breast cancer cells in vitro. Furthermore, it displayed improved accumulation in the tumor site, enhanced anticancer activity, and reduced side effects in vivo. Our results demonstrated that FA-MOF could be developed as a potential delivery system for Buf to improve its antitumor activity for breast cancer treatment.

Keywords: MOF; antitumor; breast cancer; bufalin; drug delivery; tumor targeting.