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.
The present study aimed to explore the protective effect and molecular mechanisms of Trichilia catigua A. Juss. extract (TCE) against di (2-ethylhexyl) phthalate (DEHP)-induced damage to the reproductive system of mice. Acute toxicity tests revealed that the maximum tolerated dose (MTD) in mice was up to 2.7 g kg−1. After induction with DEHP, TCE (L-TCE, M-TCE, H-TCE) was orally administered to mice for 28 days. Differences in indicators among groups showed that TCE significantly improved the anogenital distance and the organ indexes of the epididymides and testes. It also significantly reduced varicocele and interstitial cell lesions compared to the model group. H-TCE reduced the sperm abnormality rate, increased the levels of sex hormones, Na+K+ and Mg2+, Ca2+-ATPase enzyme activity, antioxidant enzyme vitality, coupled with a significant decrease in LH and MDA contents. The levels of testicular marker enzymes ACP and LDH were significantly augmented by both M-TCE and H-TCE. Further studies claimed that DEHP induction reduced the mRNA expression levels of Nrf2, SOD2, SOD3, CDC25C CDK1, CYP11A1, 3β-HSD, 5ɑ-R, AR, SF1, and CYP17A1, increased the level of Keap1, while TCE reversed the expression levels of these genes. Meanwhile, IHC results demonstrated a significant change in the expression activity of the relevant proteins compared to the control group. The results suggest that M-TCE and H-TCE enabled the recovery of DEHP-induced reproductive system damage in male mice by improving testicular histopathology, repairing testicular function, and reducing oxidative stress damage. The oxidation-related Keap1-Nrf2 pathway, SODs enzyme, the cell cycle control-related CDC25C-CDK1 pathway, and the steroidogenic-related pathway may contribute to this protective effects of TCE.
Dihydromyricetin (DHM) has garnered attention due to its promising antitumor activity, but its low bioavailability restricts its clinical application. Thus, developing nano-drug delivery systems could enhance its antitumor activity. We prepared DHM@ZIF-8 nanoparticles using the zeolite imidazole framework-8 (ZIF-8) as a carrier loaded with dihydromyricetin. A series of characterizations were performed, including morphology, particle size, zeta potential, X-single crystal diffraction, ultraviolet spectroscopy, infrared spectroscopy, and Brunauer–Emmett–Teller (BET). The in vitro release characteristics of DHM@ZIF-8 under pH = 5.0 and pH = 7.4 were studied using membrane dialysis. The antitumor activity and pro-apoptotic mechanism of DHM@ZIF-8 were investigated through CCK-8 assay, reactive oxygen species (ROS), Annexin V/PI double-staining, transmission electron microscopy, and Western blot. The results depicted that DHM@ZIF-8 possessed a regular morphology with a particle size of 211.07 ± 9.65 nm (PDI: 0.19 ± 0.06) and a Zeta potential of −28.77 ± 0.67 mV. The 24 h drug releasing rate in PBS solution at pH = 7.4 was 32.08% and at pH = 5.0 was 85.52% in a simulated tumor micro acid environment. DHM@ZIF-8 could significantly enhance the killing effect on HepG2 cells compared to the prodrug. It can effectively remove ROS from the tumor cells, promote apoptosis, and significantly affect the expression of apoptosis-related proteins within tumor cells.
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