Quercetin⁃loaded biomimetic nanoparticles induce apoptosis in colorectal cancer cells

LI Meng; YU Lingling; QIU Xinyun; WANG Wenyu; HU Bing; HAN Shulan; ZOU Yifang; GUO Jianfeng

doi:10.16306/j.1008-861x.2023.01.002

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Quercetin⁃loaded biomimetic nanoparticles induce apoptosis in colorectal cancer cells

Special column on anti-tumor of traditional Chinese medicine | 更新时间：2023-02-14

- Quercetin⁃loaded biomimetic nanoparticles induce apoptosis in colorectal cancer cells
- Academic Journal of Shanghai University of Traditional Chinese Medicine Vol. 37, Issue 1, Pages: 10-16(2023)
- 作者机构：
  
  1.吉林大学药学院（吉林　长春　130021）
- 作者简介：
- 基金信息：
- DOI：10.16306/j.1008-861x.2023.01.002
  CLC：
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李萌,余玲玲,邱新云等.载槲皮素仿生纳米粒诱导结直肠癌细胞凋亡的研究[J].上海中医药大学学报,2023,37(01):10-16.

LI Meng,YU Lingling,QIU Xinyun,et al.Quercetin⁃loaded biomimetic nanoparticles induce apoptosis in colorectal cancer cells[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2023,37(01):10-16.
李萌,余玲玲,邱新云等.载槲皮素仿生纳米粒诱导结直肠癌细胞凋亡的研究[J].上海中医药大学学报,2023,37(01):10-16. DOI： 10.16306/j.1008-861x.2023.01.002.

LI Meng,YU Lingling,QIU Xinyun,et al.Quercetin⁃loaded biomimetic nanoparticles induce apoptosis in colorectal cancer cells[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2023,37(01):10-16. DOI： 10.16306/j.1008-861x.2023.01.002.

摘要

目的,2,构建一种载槲皮素（QT）仿生纳米粒，旨在提高QT的靶向入胞效率，以提高QT对结直肠癌（CRC）细胞的抑制和凋亡作用。,方法,2,采用乳化-溶剂挥发法法制得PLGA.QT纳米粒，并在表面包覆红细胞膜（RBC）后，采用“后插入法”进行氨基乙基茴香酰胺（AEAA）靶向修饰，最终获得仿生靶向纳米粒（PLGA.QT.RBC-AEAA）。随后，对PLGA.QT.RBC-AEAA纳米粒的粒径、Zeta电位、包封率、载药量及药物释放情况等进行表征。采用激光共聚焦显微镜观察纳米粒的细胞摄取情况，分别采用MTT法和流式细胞术评价纳米粒对小鼠CRC细胞CT26的增殖抑制作用和细胞凋亡作用。,结果,2,制备得到的PLGA.QT.RBC-AEAA粒径为（107.3±7.7） nm、Zeta电位为（-17.5±0.6） mV、包封率为（65.7±5.2）%、载药量为（4.8±0.2）%，粒径小且均一，整体呈圆形，能有效装载QT。体外释放实验结果表明，PLGA.QT.RBC-AEAA纳米粒在酸性环境比在中性环境中具有更快的药物释放速率（,P,<,0.01）。此外，该仿生靶向纳米粒能促进更多的QT进入到细胞内（,P,<,0.05），并有效提高其对CT26细胞的毒性（,P,<,0.01），与游离药物相比，仿生靶向纳米粒对CT26的细胞增殖抑制率提高了近3倍。同时，与非靶向组相比，靶向纳米粒具有更强的促凋亡效果（,P,<,0.01）。,结论,2,经AEAA靶向配体修饰的PLGA.QT.RBC-AEAA纳米粒，能提高QT的靶向递送效率，增强其对CRC细胞的抑制和凋亡作用，可为今后QT体内药代动力学、药效学评价提供理论基础与实验依据。

Abstract

Objective： One kind of biomimetic nanoparticles was constructed to deliver quercetin （QT） in an attempt to improve the targeting efficiency， so as to improve the inhibitory and apoptosis effect of QT for colorectal cancer （CRC） cells.,Methods,2,PLGA.QT was prepared by emulsification-solvent evaporation method， the surface of which was coated with red blood cell membrane （RBC）， aminoethyl anisamide （AEAA） was then modified on PLGA.QT using “post-insertion” method， and biomimetic targeting nanoparticles （PLGA.QT.RBC-AEAA） were finally obtained. Then， the particle size， zeta,potential， encapsulation rate， loading capacity and drug release of PLGA.QT.RBC-AEAA nanoparticles were characterized. The cellular uptake of the nanoparticles was observed by confocal laser microscopy， and their inhibition effect of proliferation and apoptosis on mouse CRC CT26 cells were evaluated by MTT assay and flow cytometry respectively.,Results,2,The size， zeta,potential， encapsulation rate， and loading capacity of PLGA.QT.RBC-AEAA nanoparticles were （107.3±7.7） nm，（-17.5±0.6） mV，（65.7±5.2）% and （4.8±0.2）%， respectively. The nanoparticles exhibited small， spherical and uniform particle size， which could effectively encapsulate QT. ,In vitro, release experiments showed that PLGA.QT.RBC-AEAA nanoparticles had faster drug release rate in acidic environment than in neutral environment （,P,<,0.01）. In addition， the biomimetic targeting nanoparticles could promote more QT to enter into cells （,P,<,0.05）， and effectively enhance its toxicity on CT26 cells （,P,<,0.01）. Compared with the free drug， the inhibition rate of CT26 cell proliferation by biomimetic targeting nanoparticles was increased nearly 3 times. Meanwhile， compared with the non-targeting group， the targeting nanoparticles had a stronger pro-apoptotic effect （,P,<,0.01）.,Conclusion,2,The PLGA.QT.RBC-AEAA nanoparticles which modified with AEAA targeting ligand can effectively improve the targeted delivery efficiency of QT， enhance its inhibitory and apoptosis effect on CRC cells， which can provide an experimental basis for the evaluation of QT ,in vivo, pharmacokinetics and pharmacodynamics in the future.

关键词

槲皮素结直肠癌仿生纳米粒靶向递送

Keywords

quercetincolorectal cancerbiomimetic nanoparticletargeted delivery

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