HA-zein@QT纳米药物递送系统的微流控精准构建及性能研究  

Microfluidic Precise Construction and Performance Studies of HA-zein@QT Nanodrug Delivery System

作　　者：陈明慧 刘谟浩 李勇[1] 程航 耿鹏 邱昆成 邓改改[1] 曾建红[1] 黄文权 CHEN Minghui#;LIU Mohao#;LI Yong;CHENG Hang;GENG Peng;QIU Kuncheng;DENG Gaigai*;ZENG Jianhong*;HUANG Wenquan(College of Medicine and Health Science,China Three Gorges University,Yichang 443002,China;College of Materials and Chemical Engineering,China Three Gorges University,Yichang 443002,China)

机构地区：[1]三峡大学健康医学院,宜昌443002 [2]三峡大学材料与化工学院,宜昌443002

出　　处：《高等学校化学学报》2025年第3期53-62,共10页Chemical Journal of Chinese Universities

基　　金：湖北省自然科学基金(批准号:2024AFB059);三峡大学高层次人才科研启动及平台建设经费(拔尖人才)(批准号:8220309)资助。

摘　　要：玉米醇溶蛋白(Zein)在抗癌药物递送系统(DDS)中表现出巨大的潜力,但传统zein基DDS存在功能单一、粒径不均一、重现性差和抗癌效果差等缺陷.本文以槲皮素(化学药物)-TCPP(光敏剂)为模型药(QT),基于微流控技术调控载体与模型药物的共组装,精准构建了HA-zein@QT纳米药物递送系统,达到协同增效抗肿瘤的目的.采用透明质酸(HA)功能化α-zein,以提高载体的生物相容性、稳定性和细胞摄取能力.采用计算机仿真筛选出混合效率为99.54%的高效混合芯片,通过该芯片制备的HA-zein@QT平均粒径为(50.6±1.7)nm,PDI为0.196.稳定性实验表明,HA-zein@QT与去离子水、PBS缓冲溶液和1640培养基共孵育后,表现出较高的稳定性.活性氧和·OH检测结果表明,HA-zein@QT暴露于近红外光可促进^(1)O_(2)和·OH生成.生物相容性实验表明,所制备DDS与血红细胞孵育后的溶血率仅为3.75%,且与非肿瘤细胞共孵育后细胞存活率均大于84.57%,证明其具有较高的生物相容性.通过肿瘤细胞毒性研究发现,A549,HCT116和HCT8细胞的存活率分别为28.2%,20.2%和24.6%,表明HA-zein@QT对肿瘤细胞具有较高的抑制能力.本文通过微流控精准构建zein基DDS,为抗肿瘤药物的递送提供了一种高效、低毒的新策略.Zein shows great potential in anti-cancer drug delivery systems(DDS).However,the zein-based DDS prepared by the traditional method has its shortcomings,such as single function,uneven particle size,poor batch reproducibility and anti-cancer effect.In this work,the quercetin(chemical drug)-TCPP(photosensitizer)was used as the model drug(QT).The co-assembly of the carrier and the model drug was accurately controlled by microfluidic technology.And the HA-zein@QT nanodrug delivery system was precisely constructed to achieve the synergistic anti-tumor.Hyaluronic acid(HA)was used to functionalizeα-zein to improve the biocompatibility,stability and cell uptake of the carrier.The microfluidic chip with a high mixing efficiency of 99.54%was screened by computer simulation.The average particle size and PDI of the prepared HA-zein@QT were(50.6±1.7)nm and 0.196,respectively.The results of stability experiments suggested that HA-zein@QT showed high stability after co-incubation with deionized water,PBS and 1640 medium.The results of reactive oxygen species and·OH detection showed that the^(1)O_(2) and·OH increased after exposure to near-infrared light.HA-zein@QT showed a low hemolysis rate(3.75%)after co-incubation with red blood cells.And a high survival rate(>84.57%)of non-tumor cells was obtained.This evidence indicated that the prepared DDS had high biocompatibility.The cytotoxicity experiment showed that the survival rates of A549,HCT116 and HCT8 cells were 28.2%,20.2%and 24.6%,respectively.This indicated that HA-zein@QT had a high inhibitory ability to tumor cells.It is expected that the microfluidics precise construction of zein-based DDS will provide a new strategy for achieving high efficiency and minimal side effects in anti-tumor drug delivery.

关 键 词：玉米醇溶蛋白 微流控 药物递送 联合治疗 

分 类 号：O621[理学—有机化学]