Liu Hui, Wang Jingjing
Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing 400715, China.
Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices, Chongqing 400715, China.
Pharmaceutics. 2018 Jun 28;10(3):77. doi: 10.3390/pharmaceutics10030077.
Cyanine dyes are promising candidates in biomedical applications. Although various delivery systems have been developed to enhance their properties, their dendrimer-based delivery systems are seldom investigated. Herein, amine-terminated generation 5 poly(amidoamine) (G5.NH₂) dendrimers and new indocyanine green (IR820) dyes were chosen as models to study the loading ability of dendrimers for cyanine dynes. G5.NH₂ dendrimers were pre-modified with arginine-glycine-aspartic (RGD) peptides, poly(ethylene glycol) chains, and acetyl groups to be endowed with cancer cell specificity and biocompatibility. The formed Ac-PR dendrimers were used to load IR820, followed by thorough characterization. The loaded number of IR820 was estimated to be 6.7 per dendrimer. The stability of IR820 was improved through dendrimer loading, which was proved by their UV-vis spectra under different kinds of storage conditions. In addition, the formed Ac-PR dendrimers can retain the loaded IR820 effectively. Their cytocompatibility was desirable under the studied conditions. Their cellular uptake behaviors were demonstrated to be enhanced by RGD modification, showing concentration-, co-incubation time-, and αβ₃ integrin receptor-dependent properties, displaying a cytoplasm-location. The findings from this work demonstrated the versatile loading and delivery capacity of dendrimers for near-infrared (NIR) dyes, providing fundamental data for the development of dendrimer/NIR dye systems for biomedical applications, especially for cancer theranostic applications.
菁染料是生物医学应用中很有前景的候选物。尽管已经开发了各种递送系统来增强它们的性能，但基于树枝状大分子的递送系统很少被研究。在此，选择胺端基的第5代聚（酰胺胺）（G5.NH₂）树枝状大分子和新型吲哚菁绿（IR820）染料作为模型，研究树枝状大分子对菁染料的负载能力。G5.NH₂树枝状大分子用精氨酸-甘氨酸-天冬氨酸（RGD）肽、聚（乙二醇）链和乙酰基进行预修饰，以赋予其癌细胞特异性和生物相容性。将形成的Ac-PR树枝状大分子用于负载IR820，随后进行全面表征。估计每个树枝状大分子负载的IR820数量为6.7个。通过树枝状大分子负载提高了IR820的稳定性，这在不同储存条件下的紫外-可见光谱中得到了证明。此外，形成的Ac-PR树枝状大分子可以有效地保留负载的IR820。在研究条件下，它们的细胞相容性良好。它们的细胞摄取行为被证明通过RGD修饰而增强，表现出浓度、共孵育时间和αβ₃整合素受体依赖性特性，显示出在细胞质中的定位。这项工作的研究结果证明了树枝状大分子对近红外（NIR）染料具有多功能的负载和递送能力，为开发用于生物医学应用，特别是癌症诊疗应用的树枝状大分子/NIR染料系统提供了基础数据。
