Development of bionanocapsules targeting brain tumors
Development of bionanocapsules targeting brain tumors
复制标题
DOI：
10.1016/j.jconrel.2007.06.019
复制
发表时间：
2007-09-26
影响因子：
10.8
通讯作者：
Matsui, Hideki
中科院分区：
文献类型：
--
作者：
Tsutsui, Yumi;Tomizawa, Kazuhito;Matsui, Hideki
生物纳米胶囊（BNC）是由L蛋白（B病毒表面抗原）组成的中空纳米颗粒，对人肝细胞具有特异性亲和力。前S1肽展示在BNC表面上，是与人肝细胞上的受体结合的特异性配体。因此，BNC不会被递送到其他组织，例如大脑。本研究的目的是利用选择性靶向脑肿瘤的BNC开发一种新型的靶向脑肿瘤的药物递送系统（DIDS）。表皮生长因子受体（EGFR），特别是EGFR的组成型活性基因组序列缺失变体（EGFRvIII），在人胶质母细胞瘤中过表达。在本研究中，我们用蛋白A的抗体亲和基序取代前S1肽，并制备了与识别EGFRvIII的抗人EGFR抗体缀合的杂交BNC。杂交BNC被有效地递送到胶质瘤细胞，但不是正常胶质细胞。此外，我们在体内脑肿瘤模型中证实了杂交BNC向脑肿瘤的特异性递送。这些结果表明，这种使用BNC的新方法是一种有前途的脑肿瘤靶向药物递送系统。(C)2007 Elsevier B.V.保留所有权利。
Bionanocapsules (BNCs) are hollow nanoparticles that are composed of L protein (the hepatitis B virus surface antigen) and show specific affinity for human hepatocytes. The pre-S1 peptide displayed on the surface of BNCs is the specific ligand for binding to the receptor on human hepatocytes. Therefore, BNCs are not delivered to other tissues, such as the brain. The aim of the present study was to develop a novel drug delivery system (DIDS) targeting brain tumors using BNCs that selectively targeted brain tumors. Epidermal growth factor receptor (EGFR), especially a constitutively active genomic sequence deletion variant of EGFR (EGFRvIII), is overexpressed in human glioblastoma. In the present study, we replaced the pre-S1 peptide with the antibody affinity motif of protein A and made hybrid BNCs conjugated with anti-human EGFR antibody recognizing EGFRvIII. The hybrid BNCs were efficiently delivered to glioma cells but not normal glial cells. Moreover, we confirmed the specific delivery of the hybrid BNCs to brain tumors in an in vivo brain tumor model. These results suggest that this new approach using BNCs is a promising system for brain tumor-targeted drug delivery. (C) 2007 Elsevier B.V. All rights reserved.