PMID- 36080252 OWN - NLM STAT- MEDLINE DCOM- 20220912 LR - 20220913 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 27 IP - 17 DP - 2022 Aug 26 TI - Pro-Apoptotic Effect of Zeolitic Imidazolate Framework-8 (ZIF-8)-Loaded Dihydromyricetin on HepG2 Cells. LID - 10.3390/molecules27175484 [doi] LID - 5484 AB - 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. FAU - Mi, Xiao AU - Mi X AD - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China. FAU - Lu, Juan AU - Lu J AD - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China. FAU - Dong, Mingran AU - Dong M AD - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China. FAU - Lou, Yang AU - Lou Y AD - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China. FAU - Zhan, Xia AU - Zhan X AUID- ORCID: 0000-0002-3936-7809 AD - Key Laboratory of Cleaner Production and Integrated Resource Utilization of China National Light Industry, Beijing Technology and Business University, Beijing 100048, China. FAU - Chen, Xi AU - Chen X AD - Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China. LA - eng GR - No. 2021-I2M-1-022/CAMS Innovation Fund for Medical Science(CIFMS)/ PT - Journal Article DEP - 20220826 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Flavonols) RN - 0 (Reactive Oxygen Species) RN - 1318-02-1 (Zeolites) RN - KD8QND6427 (dihydromyricetin) SB - IM MH - Flavonols MH - Hep G2 Cells MH - Humans MH - Reactive Oxygen Species/metabolism MH - Renal Dialysis MH - *Zeolites/chemistry/pharmacology PMC - PMC9458003 OTO - NOTNLM OT - HepG2 cells OT - ZIF-8 OT - apoptosis OT - dihydromyricetin OT - zeolitic imidazolate framework COIS- The authors declare no conflict of interest. EDAT- 2022/09/10 06:00 MHDA- 2022/09/14 06:00 PMCR- 2022/08/26 CRDT- 2022/09/09 01:28 PHST- 2022/07/20 00:00 [received] PHST- 2022/08/22 00:00 [revised] PHST- 2022/08/23 00:00 [accepted] PHST- 2022/09/09 01:28 [entrez] PHST- 2022/09/10 06:00 [pubmed] PHST- 2022/09/14 06:00 [medline] PHST- 2022/08/26 00:00 [pmc-release] AID - molecules27175484 [pii] AID - molecules-27-05484 [pii] AID - 10.3390/molecules27175484 [doi] PST - epublish SO - Molecules. 2022 Aug 26;27(17):5484. doi: 10.3390/molecules27175484.