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  • Title: Folic Acid Decorated Zeolitic Imidazolate Framework (ZIF-8) Loaded with Baicalin as a Nano-Drug Delivery System for Breast Cancer Therapy.
    Author: Mi X, Hu M, Dong M, Yang Z, Zhan X, Chang X, Lu J, Chen X.
    Journal: Int J Nanomedicine; 2021; 16():8337-8352. PubMed ID: 34992370.
    Abstract:
    BACKGROUND: 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.
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