Glioma cell membrane camouflaged cinobufotalin delivery system for combinatorial orthotopic glioblastoma therapy  

作　　者：Zibin Song Liqian Zhao Weiyi Fang Siyun Guo Anqi Xu Zhengming Zhan Yonghua Cai ShuaiShuai Xue Peng Chai Qiuhua Jiang Peng Zhao Ye Song 

机构地区：[1]Department of Neurosurgery,Southern Medical University Nanfang Hospital,Guangzhou 510515,China [2]Institute of Brain Diseases,Nanfang Hospital of Southern Medical University,Guangzhou 510515,China [3]Cancer Center,Integrated Hospital of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510515,China [4]NMPA Key Laboratory for Research and Evaluation of Drug Metabolism Guangdong,Provincial Key Laboratory of Cardiac Function and Microcirculation Guangdong,Provincial Key Laboratory of New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou 510515,China [5]Department of Neurosurgery,Ganzhou People's Hospital,Ganzhou 341000,China

出　　处：《Nano Research》2023年第8期11164-11175,共12页纳米研究（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.81872064 and 82272879);the Natural Science Fund of Guangdong Province,China(No.2021A1515012465);Technology Program of Guangzhou(No.202206010068);Major Discipline and Academic Leader Training Program of Jiangxi Province(No.20225BCJ23001).

摘　　要：Glioblastoma(GBM)belongs to the deadliest primary malignancies with high mortality rate and poor prognosis.Over the past decades,less progress has been made to treat GBM,owing largely to the lack of effective chemotherapeutics and poor drug accumulation in the glioma tissue.In order to address this issue,we present an efficient biomimetic nanocomposite(Cu_(2−x)Se-CB@MEM,CCM),consisting of Cu_(2−x)Se nanoparticle core modified by cinobufotalin(CB),a toad venom extract,which is camouflaged with glioma cell Ln229 membrane.It is demonstrated that CB can decrease the protein activity of inosine monophosphate dehydrogenase 1(IMPDH1),a key target correlated with prognosis,through intermolecular hydrogen bonding with amino acid residues ARG-105 and ASP-77.The glioma cell membrane-camouflage endows the CCM with blood-brain barrier penetration and homology tumor-targeted ability.The optimized cinobufotalin based chemotherapy combining with the near-infrared-II(NIR-II)irradiation shows outstanding inhibition effect to glioma cells,by blocking cell cycle and inducing apoptosis.In vivo mice bearing orthotopic Ln229 GBM treated with CCM+NIR-II(CCM+L)have significantly suppressed tumor growth and extended survival,without side effect.The glioma cell membrane camouflaged nanocomposite of Cu_(2−x)Se and cinobufotalin with its significant anti-glioma property and well biosafety will provide novel alternatives for clinical treatment of GBM.

关 键 词：GLIOBLASTOMA cinobufotalin biomimetics photothermal therapy blood-brain barrier 

分 类 号：R730.5[医药卫生—肿瘤]