Abstract Thermoresponsive nanogels emerged as a robust and efficient platform for the delivery of a number of therapeutic agents. The need to deliver a wide range of biomolecules from different sizes requires a structural system with the ability to be tuned according to the specific applications. In this study, we design a library of nanogels using dendritic polyglycerol (dPG) as a crosslinker and poly (N-isopropyl acrylamide) as connecting thermoresponsive chains. Nanogels with diameters in a range of 70–210 nm were obtained by precipitation polymerization with low polydispersity. We provide a detailed study on how the flexibility of the network and size of the nanogels can be tuned by the modification of functionalities of the dPG, monomer feed and the size of the crosslinker. Additionally, we use different molecular weight proteins (6–66 kDa) as an indicator of the density of the structure by encapsulation and release experiments. We prove that the versatility of the system relays on the correct design of the nanogels and the careful selection of the starting materials and its final proportion in the reaction. By controlling the network density, a wider range of application can be achieved from a system with a short-term release triggered by temperature to a long-term release that could serve as reservoir platform.

中文翻译：

---

交联密度对热敏纳米凝胶的影响：生物大分子尺寸控制和动力学释放的研究

摘要 热响应纳米凝胶作为一种强大而有效的平台出现，可用于递送多种治疗剂。需要提供各种不同大小的生物分子，需要一种能够根据特定应用进行调整的结构系统。在这项研究中，我们设计了一个使用树枝状聚甘油 (dPG) 作为交联剂和聚（N-异丙基丙烯酰胺）作为连接热响应链的纳米凝胶库。通过具有低多分散性的沉淀聚合获得直径在 70-210 nm 范围内的纳米凝胶。我们详细研究了如何通过修改 dPG 的功能、单体进料和交联剂的大小来调整网络的灵活性和纳米凝胶的大小。此外，我们通过封装和释放实验使用不同分子量的蛋白质（6-66 kDa）作为结构密度的指标。我们证明该系统的多功能性取决于纳米凝胶的正确设计以及起始材料及其在反应中的最终比例的仔细选择。通过控制网络密度，可以实现更广泛的应用，从温度触发的短期释放系统到可作为储层平台的长期释放系统。