药物输送
体内
胶质母细胞瘤
共轭体系
树枝状大分子
纳米医学
肽
化学
癌症研究
U87型
纳米颗粒
纳米载体
薄壁组织
脑瘤
生物物理学
结合
细胞毒性
组合化学
材料科学
PEG比率
靶向给药
癌细胞
胶质瘤
纳米技术
医学
病理
生物化学
生物
生物技术
作者
Jingjing Zhao,Bo Zhang,Shun Shen,Jun Chen,Qizhi Zhang,Xinguo Jiang,Zhiqing Pang
标识
DOI:10.1016/j.jcis.2015.03.019
摘要
Glioblastoma multiforme (GBM) is the most aggressive central nervous system (CNS) tumor because of its fast development, poor prognosis, difficult control and terrible mortality. Poor penetration and retention in the glioblastoma parenchyma were crucial challenges in GBM nanomedicine therapy. Nanoparticle diameter can significantly influence the delivery efficiency in tumor tissue. Decreasing nanoparticle size can improve the nanoparticle penetration in tumor tissue but decrease the nanoparticle retention effect. Therefore, small nanoparticles with high retention effect in tumor are urgently needed for effective GBM drug delivery. In present study, a small nanoparticle drug delivery system was developed by conjugating fibrin-binding peptide CREKA to Polyamidoamine (PAMAM) dendrimer, where PEGylated PAMAM is used as drug carrier due to its small size and good penetration in tumor and CREKA is used to target the abundant fibrin in GBM for enhanced retention in tumor. In vitro binding ability tests demonstrated that CREKA can significantly enhanced nanoparticle binding with fibrin. In vivo fluorescence imaging of GBM bearing nude mice, ex vivo brain imaging and frozen slices fluorescence imaging further revealed that the CREKA-modified PAMAM achieved higher accumulation and deeper penetration in GBM tissue than unmodified one. These results indicated that the CREKA-modified PAMAM could penetrate the GBM tissue deeply and enhance the retention effect, which was a promising strategy for brain tumor therapy.
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