功能性EGF衍生物的仿生构建及其在肿瘤靶向中的应用

基于纳米材料的光热效应而发展起来的肿瘤光热疗法，因其具有可有效克服细胞耐药性、避免药物或放射治疗的毒副作用、可同步实现肿瘤热成像与治疗等优点而引起了广泛关注。另一方面，在多种肿瘤细胞表面过度表达的表皮生长因子受体(EGFR)，为纳米材料的肿瘤靶向提供了重要的靶向位点。因此，在不影响表皮生长因子(EGF)配体生物学活性的前提下，如何将EGF修饰到纳米材料表面，构建EGF配体主动靶向的纳米材料体系，提高纳米材料投递的肿瘤靶向性，具有重要的研究价值。本课题拟通过仿生海洋生物贻贝构建黏附性EGF衍生物，并用于光热纳米材料的表面修饰；研究其在纳米材料表面的黏附机制及相关影响因素；探讨由其与EGFR特异性相互作用而介导的肿瘤细胞体外/体内靶向效率和经其修饰后光热纳米材料的肿瘤热成像及抗肿瘤效果。

Due to the unique advantages, nanomaterials-based photothermal therapy showed great potential in cancer treatment. Bio-functionalization of nanomaterials with epidermal growth factor (EGF) has been applied to specific targeting cancer cells which overexpress EGF receptors (EGFR), and therefore attracted great interest in photothermal cancer therapy. However, how to functionalize EGF on the surface of nanomaterials without affecting their own biological properties is still a challenge. Inspired by mussels, an adhesive EGF derivative will be generated through solid phase peptide synthesis and genetic engineering methods, and used for surface modification of photothermal nanomaterials including single-walled carbon nanotubes and gold nanoparticles in this project. The surface modification efficiency of the prepared EGF derivative on the nanomaterials, and the cancer cell targeting ability and photothermal cancer inhibition efficiency of the modified nanaomaterials will be investigated. This project will provide a new strategy to generate adhesive biomolecules and advance the nanomaterials-based cancer targeting and photothermal therapy.