茴香酰胺修饰熊果酸自组装纳米粒制备及其通过调控CAFs抗恩杂鲁胺对前列腺癌耐药作用研究  

Preparation of anisamide-modified ursolic acid self-assembled nanoparticles and their anti-drug resistance effect of enzalutamide on prostate cancer via regulation of CAFs

作　　者：陈泠希 倪淑婷 赵文洋 陈磊[3] 胡凯莉 CHEN Ling-xi;NI Shu-ting;ZHAO Wen-yang;CHEN Lei;HU Kai-li(School of Pharmacy,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Institute of Interdisciplinary Integrative Medicine Research,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Department of Urology and Andrology,Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China)

机构地区：[1]上海中医药大学中药学院,上海201203 [2]上海中医药大学交叉科学研究院,上海201203 [3]上海中医药大学附属龙华医院泌尿男科,上海200032

出　　处：《中成药》2025年第1期28-35,共8页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金项目(82274281);上海市曙光学者计划(22SG41);上海市人才发展基金项目(201665)。

摘　　要：目的制备茴香酰胺修饰熊果酸自组装纳米粒,并评价其抗恩杂鲁胺对前列腺癌耐药作用。方法纳米沉淀法分别制备茴香酰胺修饰、未修饰自组装纳米粒,测定其粒径、Zeta电位、包封率,在透射电镜下观察形态。考察肿瘤相关成纤维细胞(CAFs)摄取,建立前列腺癌恩杂鲁胺耐药模型,CCK8法分析自组装纳米粒增敏恩杂鲁胺作用,Western blot检测NRG1、HER3、AKT表达。结果茴香酰胺修饰自组装纳米粒平均粒径为(195.13±8.06)nm,Zeta电位为(-29.07±0.55)mV,包封率为(94.58±0.84)%。CAFs对茴香酰胺修饰自组装纳米粒的摄取量高于对未修饰制剂、游离Cy5的(P<0.05),同时茴香酰胺修饰的自组装纳米粒能抑制CAFs导致的恩杂鲁胺耐药,降低CAFs上NRG1表达,且作用后的CAFs条件培养基能降低LNCaP细胞上HER3、AKT表达(P<0.05,P<0.01)。结论茴香酰胺修饰熊果酸自组装纳米粒可增加CAFs靶向性,缓解CAFs致恩杂鲁胺对前列腺癌耐药作用,降低CAFs上NRG1表达。AIM To prepare anisamide-modified ursolic acid self-assembled nanoparticles,and to evaluate their anti-drug resistance effect of enzalutamide on prostate cancer.METHODS Nanoparticle precipitation method was adopted in the preparation of anisamide-modified and non-anisamide-modified self-assembled nanoparticles,respectively,after which the particle size,Zeta potential and encapsulation efficiency were determined,and the morphology was observed under transmission electron microscope.The intake of cancer-associated fibroblasts(CAFs)was investigated,after which the model for enzalutamide resistance in prostate cancer was established,CCK8 assay was applied to analyzing the sensitization effect of self-assembled nanoparticles on enzalutamide,and Western blot was used for the detection of NRG1,HER3,AKT expressions.RESULTS The anisamide-modified self-assembled nanoparticles demonstrated the average particle size,Zeta potential and encapsulation efficiency of(195.13±8.06)nm,(-29.07±0.55)mV and(94.58±0.84)%,respectively.CAFs displayed higher intake in the anisamide-modified self-assembled nanoparticles than that in the non-modified preparation and free Cy5(P<0.05).Meanwhile,anisamide-modified self-assembled nanoparticles were able to inhibit enzalutamide resistance caused by CAFs,reduce NRG1 expression on CAFs,and anisamide-modified self-assembled nanoparticles-treated conditioned medium of CAFs could reduce HER3 and AKT expression on LNCaP cells(P<0.05,P<0.01).CONCLUSION Anisamide-modified ursolic acid self-assembled nanoparticles can enhance the targeting of CAFs,alleviate the drug resistance effect of enzalutamide on prostate cancer caused by CAFs,and reduce NRG1 expression in CAFs.

关 键 词：茴香酰胺 熊果酸 自组装纳米粒 制备工艺 恩杂鲁胺 肿瘤相关成纤维细胞(CAFs) 前列腺癌 抗耐药作用 

分 类 号：R944[医药卫生—药剂学]