Leung Kam
National Center for Biotechnology Information, NLM, NIH
Integrins are a family of cell-surface heterodimeric glycoproteins that mediate diverse biological events involving cell–cell and cell–matrix interactions (1). They consist of an α and a β subunit. They are important for cell adhesion and signal transduction. The αβ integrin plays an important role in normal lung, kidney, cerebral cortical, and epithelial development (2). On the other hand, it affects tumor growth, tumor invasiveness, and metastasis as the αβ integrin is strongly expressed on tumor cells (3, 4). D-Cys-D-Asp-Gly-HCit-Gly-Pro-Gln-D-Cys (OA02) was identified to bind to the α integrin on human ovarian cancer cells using one-bead-one-compound combinatorial libraries (5, 6). OA02 was conjugated with Cy5.5 to study biodistribution of the tracer in tumor-bearing mice (7). Cy5.5 is a NIR fluorescent dye with an absorbance maximum at 675 nm and emission maximum at 694 nm with a high extinction coefficient of 250,000 (mol/L)cm. OA02-Cy5.5 was found to have a high specific accumulation in αβ-positve ES-2 human ovarian tumor cells in nude mice. Polymeric micelles compose of a core-shell structure formed by amphiphilic block copolymers (telodendrimers) with nanoparticle sizes of 20-60 nm (8). Ligands and labels can be conjugated to the shell surface and drugs can be encapsulated inside the core of micelles. Xiao et al. (9) conjugated OA02 to micelles comprising linear copolymers of polyethylene glycol (PEG) and cholic acids (CA). Cy5.5 was conjugated to the amino group of the proximal Lys between PEG and cholic acid (CA) to form D-Cys-D-Asp-Gly-HCit-Gly-Pro-Gln-D-Cys-Ebes-Lys- PEG-CA-Cy5.5 telodendrimer nanoparticles (OA02-PEG-CACy5.5 NPs) for near-infrared (NIR) fluorescence imaging of αexpressing SKOV-3 human ovarian tumor xenografts in nude mice.
整合素是一类细胞表面异二聚体糖蛋白，介导涉及细胞间和细胞与基质相互作用的多种生物学事件（1）。它们由一个α亚基和一个β亚基组成。它们对细胞黏附和信号转导很重要。αβ整合素在正常肺、肾、大脑皮质和上皮发育中起重要作用（2）。另一方面，由于αβ整合素在肿瘤细胞上强烈表达，它会影响肿瘤生长、侵袭性和转移（3,4）。使用单珠单化合物组合文库鉴定出D-半胱氨酸-D-天冬氨酸-甘氨酸-HCit-甘氨酸-脯氨酸-谷氨酰胺-D-半胱氨酸（OA02）与人卵巢癌细胞上的α整合素结合（5,6）。OA02与Cy5.5偶联，以研究示踪剂在荷瘤小鼠体内的生物分布（7）。Cy5.5是一种近红外荧光染料，最大吸收波长为675 nm，最大发射波长为694 nm，消光系数高达250,000（mol/L）cm。发现OA02-Cy5.5在裸鼠体内的αβ阳性ES-2人卵巢肿瘤细胞中有高度特异性积聚。聚合物胶束由两亲性嵌段共聚物（端树枝状聚合物）形成的核壳结构组成，纳米颗粒尺寸为20-60 nm（8）。配体和标记物可以偶联到胶束表面，药物可以包封在胶束的核心内。Xiao等人（9）将OA02偶联到由聚乙二醇（PEG）和胆酸（CA）的线性共聚物组成的胶束上。Cy5.5偶联到PEG和胆酸（CA）之间近端赖氨酸的氨基上，形成D-半胱氨酸-D-天冬氨酸-甘氨酸-HCit-甘氨酸-脯氨酸-谷氨酰胺-D-半胱氨酸-Ebes-赖氨酸-PEG-CA-Cy5.5端树枝状聚合物纳米颗粒（OA02-PEG-CACy5.5 NPs），用于裸鼠体内表达α的SKOV-3人卵巢肿瘤异种移植瘤的近红外（NIR）荧光成像。
