Grenoble Alpes University, Centre de Recherches sur les Macromolécules Végétales (CERMAV-CNRS), 601, rue de la Chimie, BP 53, 38041 Grenoble Cedex 9, France.
Biomater Sci. 2018 Jun 25;6(7):1754-1763. doi: 10.1039/c8bm00396c.
The development of biopolymer-based nanogels has gained particular interest to achieve successful delivery of therapeutics for the treatment of various diseases, such as cancer, infection and diabetes. Herein, we report a new and simple methodology for the covalent stabilization of self-assembled gel nanoparticles based on hyaluronic acid (HA) modified with a thermoresponsive ketone-functional copolymer. This relies on the selective formation of hydrazone crosslinks with bishydrazides within the globular domains of the copolymer chains formed above the cloud point temperature. This approach allows tuning of the crosslinking density by varying the dihydrazide crosslinker to ketone molar ratio. The size distributions and morphology of the nanogels were assessed using dynamic light scattering (DLS), cryo-transmission and scanning electron microscopy. In vitro cellular uptake in several cancer cells and in vivo biodistribution of the nanogels in different mouse tumor models were then explored to assess the effectiveness of this crosslinking strategy. The data from these experiments show prolonged blood circulation, longer than 24 hours, for the crosslinked nanogels and high tumor accumulation.
基于生物聚合物的纳米凝胶的发展引起了人们的特别关注，因为它可以成功地将治疗药物递送到各种疾病（如癌症、感染和糖尿病）的治疗中。本文报道了一种新的简单方法，用于共价稳定基于透明质酸（HA）的自组装凝胶纳米颗粒，该透明质酸经过了具有温度响应性酮官能共聚改性。这依赖于在高于浊点温度形成的共聚物链的球形区域内，用双酰肼与酮之间选择性形成腙交联。这种方法可以通过改变二酰肼交联剂与酮的摩尔比来调节交联密度。使用动态光散射（DLS）、冷冻传输和扫描电子显微镜评估纳米凝胶的粒径分布和形态。然后，研究了纳米凝胶在几种癌细胞中的细胞摄取和在不同小鼠肿瘤模型中的体内生物分布，以评估这种交联策略的有效性。这些实验的数据表明，交联纳米凝胶的血液循环时间延长，超过 24 小时，并且肿瘤积累量高。
