共载藤黄酸、Fe(Ⅲ)、葡萄糖氧化酶的聚多巴胺纳米递送系统的构建及体外药效学评价  

Construction and in vitro pharmacodynamic evaluation of a polydopamine nanodelivery system co-loaded with gambogic acid,Fe(Ⅲ),and glucose oxidase

作　　者：刘剑 陈志怀 魏欣琪 林玲婷 徐伟[1] LIU Jian;CHEN Zhi-huai;WEI Xin-qi;LIN Ling-ting;XU Wei(College of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)

机构地区：[1]福建中医药大学药学院,福建福州350122

出　　处：《中国中药杂志》2025年第1期111-119,共9页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(82104406);福建省卫生健康中青年科研重大项目(2023ZQNZD017);福建省自然科学基金项目(2021J01922);福建中医药大学校管课题(X2020009-重点)。

摘　　要：藤黄酸(gambogic acid,GA)作为中药藤黄中的笼状呫吨酮类活性成分,展现出显著的抗肿瘤活性,现已进入我国肺癌治疗的临床Ⅱ期研究。然而,GA存在水溶性低、靶向性缺乏及毒副作用显著等固有缺陷,严重制约了其临床应用。新型递药系统不仅能克服上述药物缺陷,还可整合多种治疗模式,突破单一疗法的局限性。据此,该研究设计了一种以聚多巴胺(polydopamine,PDA)为基底,经聚乙二醇(polyethylene glycol,PEG)修饰通过配位作用、静电吸附和疏水相互作用依次装载Fe(Ⅲ)离子、葡萄糖氧化酶(glucose oxidase,GOx)和GA的多功能纳米递送系统[PDA-PEG-Fe(Ⅲ)-GOx-GA]。该系统表现出优异的生理稳定性、血液相容性和光热转化效率。值得注意的是,在pH和近红外光双重刺激下,PDA-PEG-Fe(Ⅲ)-GOx-GA实现了GA的可控释放,12 h累积释放率达58.3%,为无刺激条件下的3.6倍。在近红外光照射下,该系统通过PDA触发的光热效应、Fe(Ⅲ)诱导的化学动力学治疗、GOx产生的饥饿效应,以及GA介导的化疗等多重机制的协同作用,有效抑制肿瘤细胞增殖(抑制率91.5%)并诱导其凋亡(凋亡率83.3%),实现了对肺癌的多模式、多途径治疗策略。Gambogic acid(GA),a caged xanthone derivative isolated from Garcinia Hanburyi,exhibits significant antitumor activity and has advanced to phaseⅡclinical trials for lung cancer treatment in China.However,the clinical application of GA is severely hindered by its inherent limitations,including poor water solubility,a lack of targeting specificity,and significant side effects.Novel drug delivery systems not only overcome these pharmacological deficiencies but also integrate multiple therapeutic modalities,transcending the limitations of monotherapeutic approaches.In this study,we designed a multifunctional nanodelivery platform(PDA-PEG-Fe(Ⅲ)-GOx-GA)using polydopamine(PDA)as the core material.After the modification of PDA with polyethylene glycol(PEG),Fe(Ⅲ)ions,glucose oxidase(GOx),and GA were sequentially loaded via coordination interactions,electrostatic adsorption,and hydrophobic interactions,respectively.This system demonstrated excellent physiological stability,hemocompatibility,and photothermal conversion efficiency.Notably,under dual stimuli of pH and near-infrared(NIR)irradiation,PDA-PEG-Fe(Ⅲ)-GOx-GA achieved controlled GA release,with a cumulative release rate of 58.3%at 12 h,3.6-fold higher than that under non-stimulated conditions.Under NIR irradiation,the synergistic effects of PDA-mediated photothermal therapy,Fe(Ⅲ)-induced chemodynamic therapy,GOx-generated starvation therapy,and GA-mediated chemotherapy resulted in effective inhibition of tumor cell proliferation(91.5%inhibition rate)and induction of apoptosis(83.3%apoptosis rate).This multi-modal approach realized a comprehensive treatment strategy for lung cancer,integrating various therapeutic pathways.

关 键 词：聚多巴胺 藤黄酸 光热治疗 化学动力治疗 饥饿 

分 类 号：R283.6[医药卫生—中药学] R285[医药卫生—中医学]