聚单宁酸包覆的PLGA纳米粒装载β-榄香烯用于光热-化疗联合抗肿瘤的研究  

Polytannic acid coated PLGA nanoparticles loaded with β-elemene for combined chemo-photothermal therapy in cancer treatment

作　　者：阮明月 吴凯 周占荣 邓佳玲 韩丙辛 杜守颖[1] 韩宁 RUAN Ming-yue;WU Kai;ZHOU Zhan-rong;DENG Jia-ling;HAN Bing-xin;DU Shou-ying;HAN Ning(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China)

机构地区：[1]北京中医药大学中药学院,北京102488

出　　处：《中草药》2022年第23期7353-7360,共8页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金项目(81803737)。

摘　　要：目的 为了实现光热化疗联合治疗,提高抗肿瘤效果,将具有抗肿瘤作用的β-榄香烯(β-elemene,Ele)装载于聚乳酸羟基乙酸共聚物[poly(D,L-lactide-co-glycolic acid),PLGA]纳米粒(Ele-PLGA NPs)中,并在载药纳米粒表面进一步包覆了聚单宁酸(poly-tannic acid,pTA),制得Ele-PLGA-pTA纳米粒(Ele-PLGA-p TA NPs)。方法 首先利用O/W乳化法制备Ele-PLGA NPs,然后加入单宁酸与Fe3+发生络合反应,形成pTA分子层附着在Ele-PLGA NPs表面,最终形成ElePLGA-p TA NPs,通过马尔文激光粒度仪和透射电子显微镜对该系统的粒径、ζ电位、稳定性以及粒子形态进行考察;分别利用HPLC法和BCA试剂盒对β-榄香烯的载药量和单宁酸的包覆率进行测定;通过红外热成像仪评价PLGA-p TA NPs的光热升温效率和光热稳定性;通过MTT法考察载药纳米粒对Lewis肺癌细胞(Lewis lung cancer cell,LLC)的细胞毒性;通过建立小鼠LLC皮下肿瘤模型对Ele-PLGA-p TA NPs的体内光热-化疗联合抗肿瘤效果进行探究。结果 经测定,Ele-PLGAp TA NPs对β-榄香烯的载药量和单宁酸的包覆率分别为(6.6±0.1)%、(5.4±0.1)%。其形态呈球形,粒径为(202.9±2.7)nm,ζ电位为(-37.5±0.2)m V,分散性良好。体外光热性能考察结果表明,在近红外激光(NIR laser)的照射下,PLGAp TA NPs表现出良好的光热转换能力和光热稳定性。体外细胞实验结果表明,空白载体组(PLGA-pTA NPs)基本没有细胞毒性,与单一化疗组(Ele-PLGA-p TA NPs)相比,光热-化疗联合组(Ele-PLGA-p TA NPs+Laser)具有更强的细胞毒性。体内实验结果表明,与单纯光热治疗组(PLGA-p TA NPs+Laser)和单一化疗组(Ele-PLGA-pTA NPs)对照组相比,光热-化疗联合组(Ele-PLGA-p TA NPs+Laser)对小鼠肿瘤生长的抑制效果最为显著(P<0.001)。结论 所制备的Ele-PLGA-p TA NPs能够实现光热-化疗联合治疗,显著提高抗肿瘤效果。Objective To achieve combined chemo-photothermal therapy for improved anti-tumor efficacy,β-elemene(Ele) with antitumor effect was encapsulated into poly(D,L-lactide-co-glycolic acid) nanoparticles(Ele-PLGA NPs) and coated with a poly-tannic acid(pTA) layer to obtain Ele-PLGA-pTA NPs.Methods Firstly,Ele-PLGA NPs were prepared by an O/W emulsification method,then the following added with tannic acid and Fe^(3+) could coordinate with each other and form a steady pTA layer on the surface of ElePLGA NPs to obtain Ele-PLGA-pTA NPs.The prepared Ele-PLGA-pTA NPs were characterized in particle size,ζ potential,stability and morphology through DLS and TEM.The drug loading efficiency of β-elemene and the coating rate of tannic acid were quantified by HPLC and the BCA kit,respectively.In addition,the photothermal effect and photothermal stability of PLGA-pTA NPs were evaluated by an IR camera and analyzed by the FLIR software.The cytotoxicity of Ele-PLGA-pTA NPs on Lewis lung cancer cell(LLC) was investigated by MTT assay.And the in vivo anti-tumor efficacy was explored on LLC tumor bearing mice.Results For the prepared Ele-PLGA-pTA NPs,the drug loading efficiency of β-elemene and the coating rate of tannic acid were(6.6 ± 0.1)% and(5.4 ± 0.1)%,respectively.Ele-PLGA-pTA NPs were spherical in shape,the ζ potential was(-37.5 ± 0.2) mV and the particle size was(202.9 ± 2.7) nm with good dispersibility.PLGA-pTA NPs exhibited high photothermal conversion effficiency and photothermal stability.Compared to single chemotherapy(Ele-PLGA-pTA NPs),the combined chemo-photothermal therapy(Ele-PLGA-pTA NPs + Laser) showed significantly enhanced cytotoxicity,while blank control(PLGA-pTA NPs) almost had no cytotoxicity.Also,the tumor inhibition rate for the combined chemo-photothermal therapy(Ele-PLGA-pTA NPs + Laser) was much higherthan that for single chemotherapy(Ele-PLGA-pTA NPs) or photothermal therapy(PLGA-pTA NPs + Laser)(P < 0.001).Conclusion Ele-PLGA-pTA NPs prepared could achieve combined chemo-photothermal therapy and i

关 键 词：榄香烯 光热-化疗联合治疗 聚单宁酸 纳米粒 聚乳酸羟基乙酸共聚物 抗肿瘤 

分 类 号：R283.6[医药卫生—中药学]