基于复合胶束的多功能纳米药物用于探索2型糖尿病的多靶点协同治疗

2型糖尿病严重威胁着人类的生命健康，由于其发病机制涉及多种因素，如人胰岛淀粉样多肽（hIAPP）的聚集、金属离子和氧化应激等，具有复杂性和多重性，所以至今为止还没有一种切实有效的方法能够完全治愈它。本项目拟利用表面具有疏水微区的复合胶束负载天然的小分子药物白藜芦醇，并在胶束壳层修饰具有hIAPP识别能力的多肽片段SNNFGA，制备具有多功能作用的纳米药物用于2型糖尿病的多靶点协同治疗。该方案利用复合胶束表面的疏水微区与hIAPP结合，抑制hIAPP的聚集；通过修饰SNNFGA，提高复合胶束对hIAPP的选择性结合能力，有助于2型糖尿病的特异性治疗；利用复合胶束的有效负载，提高白藜芦醇的水溶性和稳定性，并使复合胶束拥有白藜芦醇抗氧化和螯合金属的能力，从而达到“一体多效”的目的。这种多功能的纳米药物将为2型糖尿病的高效治疗提供新的思路，同时也为新型2型糖尿病药物的开发研制提供重要理论依据。

Type II diabetes is a serious threat to human health. However, there are no effective treatments that can cure the disease due to the complicated pathogenesis that involving numerous factors such as human islet amyloid polypeptide (hIAPP) aggregation, metal ion and reactive oxygen species. This project aims to develop a multifunctional nanomedicine based on complex micelles for multi-targeted and synergistic treatment of type II diabetes. This kind of complex micelles possess hydrophobic micro-domains on the surface, which are formed by the straightforward self-assembly of two diblock copolymers and encapsulated with natural small molecule drug resveratrol. Moreover, the PEG chains of complex micelles are modified by peptides fragments SNNFGA which have hIAPP recognition capability. The hydrophobic micro-domains of complex micelles can act as anchors for interacting with hIAPP and thereby inhibit hIAPP aggregation. SNNFGA modification onto the micelles surface can improve the ability of complex micelles for selectively binding hIAPP, which contribute to the specific treatment of type II diabetes. Meanwhile, the encapsulation of resveratrol by complex micelles can not only improve the water solubility and stability of free resveratrol, but also make complex micelles have capacity to attenuate oxidative stress and chelate metal ions, achieving the purpose of multiple effects in one. This kind of multifunctional nanomedicine based on complex micelles will provide new idea and approach for efficient treatment of type II diabetes, as well as offer important theoretical basis for design and development of novel type II diabetes drugs.