Small peptide-modified nanostructured lipid carriers distribution and targeting to EGFR-overexpressing tumor in vivo
Small peptide-modified nanostructured lipid carriers distribution and targeting to EGFR-overexpressing tumor in vivo
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小肽修饰的纳米结构脂质载体分布和体内靶向 EGFR 过表达肿瘤
DOI：
10.3109/21691401.2013.801848
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发表时间：
2014-06-01
影响因子：
5.8
通讯作者：
Pan, Weisan
中科院分区：
文献类型：
--
作者：
Han, Cuiyan;Li, Yao;Pan, Weisan
摘要丙氨酸-谷氨酸-酪氨酸-亮氨酸-精氨酸(Ala-Glu-Tyr-Leu-Arg，AEYLR)是我们前期研究中发现的一种体外靶向表皮生长因子受体(EGFR)的小肽配体。本文研究了AEYLR及其偶联纳米脂质载体(NLC)的体内靶向性。制备了近红外荧光染料1，1‘-二十八烷基四甲基吲哚菁碘(DIR)和AEYLR修饰的NLC(A-D-NLC)。用AEYLR和NLC的平均直径、Zeta电位、偶联效率和A-D-NLC释放的dir量来评价它们的体内特性。用Cy7标记AEYLR，建立A549荷瘤小鼠模型。分别于注射后不同时间用NIRF显像法检测A-D-NLC和Cy7-AEYLR在荷瘤小鼠体内的分布。与对照组相比，AEYLR和AEYLR偶联的NLC对A549移植瘤具有明显的靶向性。这些结果表明，AEYLR修饰的NLC有望成为肿瘤联合化疗的靶向给药系统，以提高疗效和减少不良反应。
Abstract Ala-Glu-Tyr-Leu-Arg (AEYLR) was identified as a small peptide ligand targeting epidermal growth factor receptors (EGFR) in vitro in our previous study. The in vivo targeting ability of AEYLR and AEYLR-conjugated nanostructured lipid carriers (NLC) was studied in this paper. Near-infrared fluorescent (NIFR) dye 1,1’-dioctadecyltetramethyl indotricarbocyanine iodide (DiR)-loaded and AEYLR-modified NLC (A-D-NLC) were prepared. The average diameter, zeta potential, coupling efficiency between AEYLR and NLC and the amount of DiR released from A-D-NLC were used to evaluate their in vivo characteristics. AEYLR was labeled by Cy7 and A549 xenograft tumor-bearing mice model were establish. The in vivo distribution in tumor-bearing mice of A-D-NLC and Cy7-AEYLR was examined using NIRF imaging experiments at different times post-injection. AEYLR and AEYLR-conjugated NLC showed obvious targeting to A549 xenograft tumor compared with the control group. These results suggested that AEYLR-modified NLC could be considered as a promising targeted delivery system for combination cancer chemotherapy to improve therapeutic efficacy and to minimize adverse effects.