新型非酶可降解碳基纳米颗粒及其抗肿瘤研究

无机纳米药物的不可降解性与靶向性问题已成为制约其临床转化应用的关键难题。虽然酶促降解策略推动了可降解碳基材料领域的发展，但仍存在反应条件较严苛、易诱发体内副作用等局限性。为此，申请人拟以介孔二氧化硅颗粒（MSN）为载体负载碳结构创新构建出一种新型碳基纳米颗粒(CSN)，并采用基因修饰后高表达EGF的间充质干细胞膜作为仿生细胞膜进行伪装(EGF-MSC-CSN)。该颗粒可伴随MSN降解失去支撑崩塌成小尺寸组分，易于从体内代谢；兼具光热/光动力结合的双光疗性质；同时融合主动靶向、被动靶向与间充质干细胞肿瘤归巢性于一体的多重靶向特性。本研究将结合临床病人肿瘤标本建立人源性肿瘤异种移植（PDX）模型，精确评价其有效性、安全性和靶向性。本项目将为构建可降解纳米体系开辟新思路，有望推动碳基纳米光疗剂的临床推广，对提高我国肿瘤精准治疗研究水平具有十分重要意义。

The non-degradability and targeting of inorganic nano-drugs have become key problems restricting their clinical applications. Although the enzymatic degradation strategy has promoted the development of biodegradable carbon-based materials, there are still limitations such as strict reaction conditions and in vivo side effects. Therefore, the applicant intends to construct an enzyme-free degradable carbon-based nanomaterial (CSN) using mesoporous silica nanoparticle (MSN) as the carrier to load carbon structure, and use the EGF gene modified mesenchymal stem cell membrane to camouflage (EGF-MSC-CSN).The nanoparticles can undergo an enzyme-free degradation process into small particles, which are easy to be metabolized from the body. The nanoparticles not only harbor the photothermal and photodynamic properties, but also own multiple tumor-targeting capability. In this study, patient-derived xenograft (PDX) tumor models will be established to accurately evaluate its effectiveness, safety and targeting. This project will open a new window for the construction of biodegradable nano-systems, and will benefit the possible clinical translation of carbon-based nanomaterials. In addition, there is of great significance for improving the research level of precision treatment of tumors in China.