Self-assembly of Hyaluronic Acid-Cu- Quercetin flavonoid nanoparticles: synergistic chemotherapy to target tumors

作者全名："Yue, Hanxun; Zhao, Xuan; Yong, Qin; Shi, Min; Jiang, Xiaofeng; Zhang, Yating; Yu, Xian"

作者地址："[Yue, Hanxun; Zhao, Xuan; Yong, Qin; Shi, Min; Jiang, Xiaofeng; Zhang, Yating; Yu, Xian] Chongqing Med Univ, Affiliated Hosp 2, Phase Clin Trial Ctr 1, Chongqing, Peoples R China; [Yue, Hanxun] First Peoples Hosp Pingdingshan, Pingdingshan 467002, Peoples R China"

通信作者："Yu, X (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Phase Clin Trial Ctr 1, Chongqing, Peoples R China."

来源：PEERJ

ESI学科分类：Multidisciplinary

WOS号：WOS:001059213000002

JCR分区：Q2

影响因子：2.3

年份：2023

卷号：11

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Quercetin; Quercetin-copper complex; Flavonoid self-assembled nanoparticles; Fenton-like reaction; Synergistic antitumor

摘要："Background: In this study, a natural compound quercetin (Qu) was investigated for its various antitumor effects. However, due to its poor water solubility and low bioavailability, its clinical application is limited. To overcome this constraint, a modification was to Qu, which resulted in the creation of novel flavonoid self-assembling nanoparticles (HCQ NPs).Methods: HCQ NPs were synthesized by a self-assembly method and characterized using transmission electron microscopy, the Malvern Zetasizer instrument, X-ray photoelectron spectroscopy (XPS), the ultraviolet-visible spectrophotometric method (UV-vis), Fourier transform infrared (FITR) and inductively coupled plasma mass spectrometry. Extracellular, methylene blue spectrophotometric analysis was used to determine the ability of HCQ NPs to react with different concentrations of H2O2 to form hydroxyl radicals ('OH). Intracellular, DCFH-DA staining was used to detect the ability of HCQ NPs to react with H2O2 to generate reactive oxygen species. Flow cytometry was used to detect the uptake of HCQ NPs by MDA-MB-231 cells at different time points. The biocompatibility of HCQ NPs was evaluated using the Cell Counting Kit-8 (CCK-8) assay. Calcein AM/PI double staining and the CCK-8 assay were used to evaluate the synergistic antitumor effect of HCQ NPs and H2O2.Results: HCQ NPs showed uniformly sized analogous spherical shapes with a hydrodynamic diameter of 55.36 & PLUSMN; 0.27 nm. XPS revealed that Cu was mainly present as Cu2+ in the HCQ NPs. UV-vis absorption spectrum of the characteristic peak of HCQ NPs was located at 296 nm. Similarly, FTIR spectroscopy revealed a complex formation of Qu and Cu2+ that substantially changed the wavenumber of the 4-position C = O characteristic absorption peak. Based on the proportion of Qu and Cu2+ (1:2), the total drug loading of Qu and Cu2+ in the HCQ NPs for therapeutic purposes was calculated to be 9%. Methylene blue spectrophotometric analysis of 'OH indicated that Cu can lead to the generation of 'OH by triggering Fenton-like reactions. HCQ NPs rapidly accumulated in MDA-MB-231 cells with the extension of time, and the maximum accumulation concentration was reached at about 0.5 h. Calcein AM/PI double staining and CCK-8 revealed synergistic antitumor effects of HCQ NPs including the chemotherapeutic effect of Qu and chemodynamic therapy by Cu2+ in a simulated tumor microenvironment. HCQ NPs demonstrated very low toxicity in LO2 cells in the biocompatibility experiment.Conclusion: This study show cases a new method of creating self-assembled flavonoid HCQ NPs that show great for fighting cancer."

基金机构：National Natural Science Foundation of China [CSTB2022NSCQ-MSX0987]; Chongqing Natural Science Foundation; Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University; [82072327]

基金资助正文："This work was financially supported by the National Natural Science Foundation of China (NO. 82072327) , the Chongqing Natural Science Foundation CSTB2022NSCQ-MSX0987, and the Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."