Dendrimer-Assisted Formation of Fluorescent Nanogels for Drug Delivery and Intracellular Imaging

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• 作者：Mara Gon?alves ; Dina Maciel ; Débora Capelo ; Shili Xiao ; Wenjie Sun ; Xiangyang Shi ; Jo?o Rodrigues ; Helena Tomás ; Yulin Li
• 刊名：Biomacromolecules
• 出版年：2014
• 出版时间：February 10, 2014
• 年：2014
• 卷：15
• 期：2
• 页码：492-499
• 全文大小：572K
• ISSN：1526-4602

文摘

Although, in general, nanogels present a good biocompatibility and are able to mimic biological tissues, their unstability and uncontrollable release properties still limit their biomedical applications. In this study, a simple approach was used to develop dual-cross-linked dendrimer/alginate nanogels (AG/G5), using CaCl₂ as cross-linker and amine-terminated generation 5 dendrimer (G5) as a cocrosslinker, through an emulsion method. Via their strong electrostatic interactions with anionic AG, together with cross-linker Ca²⁺, G5 dendrimers can be used to mediate the formation of more compact structural nanogels with smaller size (433 卤 17 nm) than that (873 卤 116 nm) of the Ca²⁺-cross-linked AG nanogels in the absence of G5. Under physiological (pH 7.4) and acidic (pH 5.5) conditions, the sizes of Ca²⁺-cross-linked AG nanogels gradually decrease probably because of their degradation, while dual-cross-linked AG/G5 nanogels maintain a relatively more stable structure. Furthermore, the AG/G5 nanogels effectively encapsulate the anticancer drug doxorubicin (Dox) with a loading capacity 3 times higher than that of AG nanogels. The AG/G5 nanogels were able to release Dox in a sustained way, avoiding the burst release observed for AG nanogels. In vitro studies show that the AG/G5-Dox NGs were effectively taken up by CAL-72 cells (a human osteosarcoma cell line) and maintain the anticancer cytotoxicity levels of free Dox. Interestingly, G5 labeled with a fluorescent marker can be integrated into the nanogels and be used to track the nanogels inside cells by fluorescence microscopy. These findings demonstrate that AG/G5 nanogels may serve as a general platform for therapeutic delivery and/or cell imaging.