Development of a Screening System for Targeting Carriers Using Peptide-Modified Liposomes and Tissue Sections.
Development of a Screening System for Targeting Carriers Using Peptide-Modified Liposomes and Tissue Sections.
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DOI：
10.1248/bpb.b18-00151
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发表时间：
2018-07
影响因子：
2
通讯作者：
Y. Negishi;N. Hamano;Hinako Sato;Fumihiko Katagiri;K. Takatori;Y. Endo-Takahashi;Y. Kikkawa;M. Nomizu
中科院分区：
文献类型：
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作者：
Y. Negishi;N. Hamano;Hinako Sato;Fumihiko Katagiri;K. Takatori;Y. Endo-Takahashi;Y. Kikkawa;M. Nomizu
脂质体已被用作药物递送系统（DDS）的靶向载体，并且载体能够用靶向配体（例如抗体和肽）进行修饰。为了评估用靶向配体修饰的 DDS 载体的靶向性，使用表达靶向分子的培养细胞以及小动物。此外，必须重复进行体外和体内筛选分析。因此，建立一种简便、高精度的靶向载体筛选系统具有重要意义。为此，我们重点关注该离体系统是否能够轻松支持生理环境下靶向配体与其受体之间相互作用的评估，并进一步筛选靶向部分修饰的DDS载体。我们使用整合素 αvβ3 靶向 C16Y-L 通过体外、离体和体内分析检查了靶向能力。对于体外分析，C16Y-L在结肠26细胞中的细胞摄取高于对照脂质体。对于离体分析，我们使用 colon26 肿瘤切片进行了免疫组织化学分析。正如体外分析中发现的那样，C16Y-L 特异性地附着在肿瘤切片上。此外，为了评估离体-体内相关性，我们检查了 C16Y-L 的瘤内定位。该结果表明，静脉注射C16Y-L后，C16Y-L不仅在肿瘤组织中积累，而且在肿瘤脉管系统中积累，表明离体肽修饰脂质体分析与体内分析相关。因此，离体肽修饰脂质体分析可能是一种简单、快速的高精度筛选系统，并且适合在体内条件下考虑。
Liposomes have been used as targeting carriers for drug delivery systems (DDSs), and the carriers are able to be modified with targeting ligands, such as antibodies and peptides. To evaluate the targetability of DDS carriers modified with a targeting ligand, culture cells expressing the targeting molecules as well as small animals are used. Furthermore, in vitro and in vivo screening analyses must be repeatedly performed. Therefore, it is important to establish an easy and high-precision screening system for targeting carriers. With this aim, we focused that whether this ex vivo system could easily support assessment of interaction between targeting ligand and its receptor under physiological environment and further screen the DDS carrier-modified with targeting moiety. We examined targeting ability via in vitro, ex vivo, and in vivo analyses using integrin αvβ3-targeting C16Y-L. For the in vitro analysis, the cellular uptake of C16Y-L was higher than that of control liposomes in colon26 cells. For the ex vivo analysis, we performed an immunohistochemical analysis using colon26 tumor sections. C16Y-L was specifically attached to the tumor sections, as found in the in vitro analysis. Moreover, to evaluate the ex vivo-in vivo correlation, we examined the intratumoral localization of C16Y-L. This result showed that C16Y-L was accumulated not only in the tumor tissue but also in the tumor vasculature after the intravenous injection of C16Y-L, suggesting that the ex vivo peptide-modified liposomal analysis was correlated with the in vivo analysis. Thus, the ex vivo peptide-modified liposomal analysis may be an easy and rapid screening system with high-precision and for consideration in in vivo conditions.