二维光热转换纳米载体的仿生合成及双模式一体化肿瘤诊疗

Compared with traditional zero-dimensional (0D) and one-dimensional (1D) photothermal conversion materials (PCMs), two-dimensional (2D) PCMs showed obvious advantages such as larger specific surface area, higher photothermal conversion efficiency, and easier modification, which exhibited potential applications in both chemotherapy and photothermal therapy. However, these inorganic 2D PCMs revealed low biocompatibility, degradability, and targeting abilities, which limited their extended applications in biomedical fields. In this project, we aim to synthesize 2D peptide nanosheets (PNS) with biomimetic ability and cell-targeting function through designing and tailoring peptide sequences, and then prepare 2D organic-inorganic hybrid PNS-based PCMs by biomimetic synthesis. Taking liver cancer cells and mouse with liver cancers as models, the therapy mechanisms of the created 2D PNS-based PCMs towards cancers will be explored through the integration of dual-mode chem-photothermal theranostics. This project will be helpful to understand the design, functional tailoring, and 2D supramolecular self-assembly mechanisms of various designed peptides, and to explore the controllable preparation strategies of 2D PNS and their biomimetic synthesis of PCMs. In addition, it will be valuable for us to develop novel bio-nanocarriers with high biocompatibility, high degradability, accurate cancer-targeting, controllable photothermal and chemical therapeutic effects for clinical applications, and provide new ideas and methods to achieve in the accurate and visual theranostics of cancers.

与传统的零维及一维光热转换材料相比，二维材料具有更大的比表面积、更高的光热转换效率以及更易于修饰等优点，在肿瘤化学、光热诊疗方面有巨大潜能。然而，这些无机二维光热转化材料通常具有低的生物相容性、降解性和靶向性等缺点。本项目拟通过多肽序列设计及功能调控，合成具有仿生能力及细胞靶向功能的二维多肽纳米片，进而利用仿生合成手段制备二维有机-无机杂化光热转换纳米载体。以肝癌细胞及小鼠肝癌模型为研究对象，利用光热、化学双模式一体化诊疗，探索二维仿生纳米载体的一体化诊疗机理及协同增效机制。本项目的开展将有利于进一步理解多肽分子的序列设计、功能调控以及超分子自组装机理，探索二维多肽纳米结构的可控制备以及仿生合成机理。同时也将有助于开发新型的具有高生物相容性、高降解性、精准细胞靶向识别、可控光热及化学诊疗效果的生物纳米载体材料，并应用于临床研究，为实现精准可视化肿瘤诊疗提供新的思路和方法。

由于多肽分子的高生物相容性、可降解性、自组装特性以及仿生合成等多方面的优势，自组装多肽纳米材料在肿瘤光热及化学诊疗方面具有非常重要的意义。在项目执行期内，我们按照项目计划书的原定计划和要求认真负责的完成了与项目相关的课题研究。通过自主设计多种功能化多肽分子，我们研究了多肽分子在各种实验体系下的自组装，制备了多种具有高生物相容性、降解性、仿生性质的多肽纳米纤维、多肽纳米带、多肽纳米片，并研究了多肽分子的自组装机理；以制备的多肽纳米材料为基本结构单元，利用仿生合成方法，我们成功合成了多种具有纳米酶活性、催化活性、光热转换能力的杂化纳米材料；以仿生合成的多肽纳米材料为基础，我们进一步构建了肿瘤化学诊疗和光热诊疗为一体的纳米平台；通过体外和体内生物实验，我们探索了基于多肽的二维仿生纳米材料在肿瘤诊疗方面的潜在应用，为进一步开发具有实时成像、化学诊疗、光热诊疗为一体的功能纳米药物载体提供了潜在策略，同时为肿瘤的一体化诊疗提供了新的思路和方法。团队成员在国内外期刊，如Chem Soc Rev, Chem Eng J, ACS Nano, Nanoscale等发表高水平论文27篇，撰写英文章节2章，项目组成员参加学术会议5人次，发表会议论文5篇。通过该项目的资助，共培养博士研究生4人，硕士研究生10人。