白蛋白-吲哚菁绿纳米粒子用于成像引导的肿瘤靶向光热治疗研究

Cancer is one of the most pressing public health concerns. Photothermal therapy (PTT) has emerged as an alternative strategy for the treatment of cancer. Some key requirements for clinical translation of such constructs are that they must be non-toxic, non-immunogenic, biodegradable, with extended circulating lifetime. The focus of this project was the development of tumor-targeting nanoparticles (NPs) containing photosensitizers for efficient PTT and imaging. Human serum albumin (HSA), the most abundant protein in plasma was used to encapsulate indocyanine green (ICG), the only FDA-approved near infrared chromophore. HSA-ICG NPs have the potential to serve not only as an efficient contrast agent for near-infrared (NIR) /photoacoustic (PA) imaging agents, but also as photothermal destruction reagents in cancer treatment. We investigate the biocompatibility, safety, stability, selectivity，sensitivity and the NIR/PA imaging of ICG-HSA NPs in living mice. We further investigate the photothermal therapy effect of ICG-HSA NPs after a single dose treatment in vivo. ICG-HSA NPs has the potential as photothermal destruction reagents in cancer treatment, which greatly increases the chances for successful treatment and has a significant effect on clinical management.

本项目面向癌症治疗的重大需求，针对肿瘤光热治疗过程中外源性有机纳米光热试剂存在的两大难题：（1）大多缺乏肿瘤主动靶向性；（2）体内代谢途径尚不明确。拟采用生物还原法一步合成体内可自然新陈代谢的双靶向白蛋白-吲哚菁绿（HSA-ICG）纳米粒子，利用荧光活体成像系统/光声成像平台，深入研究HSA-ICG纳米粒子的体外/体内行为规律和与癌细胞的相互作用。在此基础上，通过乳腺癌荷瘤小鼠模型，研究HSA-ICG纳米粒子对乳腺癌的靶向光热治疗效应，并通过肿瘤的成像对疗效进行实时评估。本项目的研究不仅为癌症的治疗提供新手段和新方法，同时对其他疾病的治疗也具有十分重要的方法学意义。

本项目面向癌症早期诊断和治疗的重大需求，针对肿瘤光热治疗过程中外源性有机纳米光热试剂存在的两大难题：（1）大多缺乏肿瘤主动靶向性；（2）成像灵敏度低。采用生物还原法、蛋白自组装法、超声剥离法等方法，制备稳定的、生物相容的、肿瘤靶向的高灵敏的白蛋白吲哚菁绿纳米探针、白蛋白-二氢卟酚纳米探针、HSA-MB-ICG纳米粒子、聚多巴胺还原氧化石墨烯纳米探针、吲哚菁绿聚多巴胺纳米探针、二硫化钼纳米片等；利用荧光活体成像系统/光声成像平台，深入研究纳米粒子的体外/体内行为规律和与癌细胞的相互作用。在此基础上，通过乳腺癌荷瘤小鼠模型，研究纳米粒子对肿瘤的靶向光热治疗效应，并通过肿瘤的成像对疗效进行实时评估。本项目共计发表JCR一区SCI论文13篇，申请发明专利8项，培养了1名高级工程师，1名博士研究生。本项目的研究不仅为癌症的治疗提供新手段和新方法，同时对其他疾病的治疗也具有十分重要的方法学意义。