Insulin therapy plays an essential role in the treatment of diabetes mellitus. However, frequent injections required to effectively control the glycemic levels lead to substantial inconvenience and low patient compliance. In order to improve insulin delivery, many efforts have been made, such as developing the nanoparticles (NPs)-based release systems and oral insulin. Although some improvements have been achieved, the ultimate results are still unsatisfying and none of insulin-loaded NPs systems have been approved for clinical use so far. Recently, nano‒protein interactions and protein corona formation have drawn much attention due to their negative influence on the in vivo fate of NPs systems. As the other side of a coin, such interactions can also be used for constructing advanced drug delivery systems. Herein, we aim to provide an insight into the advance and flaws of various NPs-based insulin delivery systems. Particularly, an interesting discussion on nano‒protein interactions and its potentials for developing novel insulin delivery systems is initiated.

胰岛素疗法在糖尿病的治疗中起着至关重要的作用。然而，有效控制血糖水平所需的频繁注射导致极大的不便和患者依从性低。为了改善胰岛素的输送，已经进行了许多努力，例如开发基于纳米颗粒（NP）的释放系统和口服胰岛素。尽管已经取得了一些进步，但最终结果仍然令人不满意，并且迄今为止，尚未批准将装有胰岛素的NPs系统用于临床。近年来，由于纳米‒蛋白相互作用和蛋白电晕的形成对体内的负面影响，引起了人们的广泛关注。NP系统的命运。作为硬币的另一面，这种相互作用也可以用于构建先进的药物输送系统。在此，我们旨在提供各种基于NPs的胰岛素输送系统的先进性和缺陷的见解。特别是，开始了有关纳米蛋白质相互作用及其开发新型胰岛素输送系统潜力的有趣讨论。