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载有白杨素的壳聚糖-叶酸包被固体脂质纳米粒在胰腺癌细胞中的靶向递送及抗癌作用

Targeted delivery and anticancer effects of Chrysin-loaded chitosan-folic acid coated solid lipid nanoparticles in pancreatic malignant cells.

作者信息

Farhadi Amin, Homayouni Tabrizi Masoud, Sadeghi Soroush, Vala Danial, Khosravi Tina

机构信息

Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran.

出版信息

J Biomater Sci Polym Ed. 2023 Feb;34(3):315-333. doi: 10.1080/09205063.2022.2121589. Epub 2022 Sep 12.

Abstract

The aim of this survey was to load Chrysin (CHY) on solid lipid nanoparticles (SLNs) and decorate the nanoparticles with folate-bound chitosan to increase the effectiveness of the treatment. CHY-SCF-NPs were synthesized by homogenizing and sonication methods and characterized. FA binding and encapsulation efficiency (HPLC), antioxidant capacity (ABTS and DPPH), cell viability assay (MTT), programmed cell death analysis (fluorescence staining, flow cytometry, and qPCR), and angiogenesis (CAM and molecular analysis) assay were done for assessment of therapeutic efficiency of CHY-SCF-NPs. Increases in size and change in surface charge of CHY-SLNs (PS: 84.3 nm and ZP: -18 mV) were reported after coating with folate-bound chitosan (PS: 125 nm and ZP: +34.9 mV). CHY-SCF-NPs inhibited PANC, MCF-7, A2780, and HepG2 as malignant cells and HFF as normal cells with IC∼53, 55, 249, and >250 µg/mL, respectively. Also, CHY-SCF-NPs scavenged ABTS (IC: 123.73 µg/mL), and DPPH (IC: 108.7 µg/mL) free radicals and suppressed angiogenesis in the CAM and qPCR assays. Up-regulation of Bax and caspase 9 genes as well as the fluorescence staining and cell cycle results confirmed the pro-apoptotic properties of CHY-SCF-NPs. CHY-SCF-NPs can be considered a promising anti-cancer candidate for preclinical and clinical studies of pancreatic cancer.

摘要

本研究旨在将白杨素(CHY)负载于固体脂质纳米粒(SLNs)上,并用叶酸偶联壳聚糖修饰纳米粒,以提高治疗效果。通过均质化和超声处理方法合成并表征了CHY-SCF-NPs。采用FA结合和包封率(HPLC)、抗氧化能力(ABTS和DPPH)、细胞活力测定(MTT)、程序性细胞死亡分析(荧光染色、流式细胞术和qPCR)以及血管生成(鸡胚绒毛尿囊膜实验和分子分析)实验来评估CHY-SCF-NPs的治疗效果。结果显示,用叶酸偶联壳聚糖包被后,CHY-SLNs的粒径增大(PS:84.3 nm)且表面电荷改变(ZP:-18 mV),变为CHY-SCF-NPs(PS:125 nm,ZP:+34.9 mV)。CHY-SCF-NPs对胰腺癌细胞PANC、乳腺癌细胞MCF-7、卵巢癌细胞A2780和肝癌细胞HepG2具有抑制作用,对正常细胞人包皮成纤维细胞HFF也有抑制作用,其IC50分别约为53、55、249和>250 μg/mL。此外,CHY-SCF-NPs在ABTS(IC50:123.73 μg/mL)和DPPH(IC50:108.7 μg/mL)自由基清除实验以及鸡胚绒毛尿囊膜实验和qPCR实验中均显示出抑制血管生成的作用。Bax和caspase 9基因的上调以及荧光染色和细胞周期结果证实了CHY-SCF-NPs的促凋亡特性。CHY-SCF-NPs有望成为胰腺癌临床前和临床研究中有前景的抗癌候选药物。

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