International Journal of Nanomedicine (Dec 2021)
Folic Acid Decorated Zeolitic Imidazolate Framework (ZIF-8) Loaded with Baicalin as a Nano-Drug Delivery System for Breast Cancer Therapy
Abstract
Xiao Mi,1 Meigeng Hu,1 Mingran Dong,1 Zhihong Yang,1 Xia Zhan,2 Xinyue Chang,1 Juan Lu,1 Xi Chen1 1Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100094, People’s Republic of China; 2Key Laboratory of Cleaner Production and Integrated Resource Utilization of China National Light Industry, Beijing Technology and Business University, Beijing, 100048, People’s Republic of ChinaCorrespondence: Xi Chen; Juan LuInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100094, People’s Republic of ChinaTel +86 10-57833257Email [email protected]; [email protected]: Baicalin (BAN) has attracted widespread attention due to its low-toxicity and efficient antitumor activity, but its poor water solubility and low bioavailability severely limit its clinical application. Development of a targeted drug delivery system is a good strategy to improve the antitumor activity of baicalin.Methods: We prepared a BAN nano-drug delivery system PEG-FA@ZIF-8@BAN with a zeolite imidazole framework-8 (ZIF-8) as a carrier, which can achieve the response of folate receptor (FR). We characterized this system in terms of morphology, particle size, zeta-potential, infrared (IR), ultraviolet (UV), x-ray diffraction (XRD), and Brunel-Emmett-Teller (BET), and examined the in vitro cytotoxicity and cellular uptake properties of PEG-FA@ZIF-8@BAN using MCF-7 cells. Lastly, we established a 4T1 tumor-bearing mouse model and evaluated its in vivo anti-mammary cancer activity.Results: The PEG-FA@ZIF-8@BAN nano-delivery system had good dispersion with a BAN loading efficiency of 41.45 ± 1.43%, hydrated particle size of 176 ± 8.1 nm, Zeta-potential of − 23.83 ± 1.1 mV, and slow and massive drug release in an acidic environment (pH 5.0), whereas release was 11.03% in a neutral environment (pH 7.4). In vitro studies showed that PEG-FA@ZIF-8@BAN could significantly enhance the killing effect of BAN on MCF-7 cells, and the folic acid-mediated targeting could lead to better uptake of nanoparticles by tumor cells and thus better killing of cancer cells. In vivo studies also showed that PEG-FA@ZIF-8@BAN significantly increased the inhibition of the proliferation of solid breast cancer tumors (p < 0.01 or p < 0.001).Conclusion: The PEG-FA@ZIF-8@BAN nano-drug delivery system significantly enhanced the anti-breast cancer effect of baicalin both in vivo and in vitro, providing a more promising drug delivery system for the clinical applications and tumor management.Keywords: metal-organic framework, folic acid response, baicalin, breast cancer therapy
