产生非氧依赖性自由基的纳米梭用于乳腺癌分级靶向及光热/热动力联合治疗

随着乳腺癌患者对保乳治疗疗效的要求逐步提高，探索新的微创诊疗策略具有重要意义。基于纳米粒产生自由基杀伤肿瘤的光动力疗法，以微创的优势备受关注。但由于肿瘤内环境乏氧、纳米粒在瘤内富集不足、靶向率低等问题，严重阻碍了自由基的治疗效果。氧无关的自由基生成策略就显示出了巨大的潜力。我们在前期研究初步证实了热引发剂V057可在肿瘤内乏氧的环境下，通过吲哚箐绿（ICG）的光热效应热触发分解产生自由基，杀伤乳腺癌细胞。在此基础上，本项目将以铁掺杂聚二氨基吡啶纳米体为载体，研发包裹聚乙二醇的载V057及ICG的纳米梭。依靠其梭型结构和表面电位翻转的特点，分级靶向到肿瘤细胞及胞内线粒体，提高瘤内蓄积。再通过光热触发纳米梭产生自由基，启动对乳腺癌的光热/热动力联合治疗；同时，具有一定的多模态成像效果。通过探索纳米梭的靶向性能及其杀灭乳腺肿瘤的机制、疗效和成像特点，有望为乳腺癌的诊疗提供一个新的研究视角和策略。

With the increasing demand of breast cancer patients for breast conserving therapy, it is of great significance to explore new minimally invasive diagnostic and therapeutic strategies. Photodynamic therapy (PDT) based on free radicals produced by nanoparticles has attracted much attention due to its advantages of minimally invasive. However, due to the lack of oxygen in tumor environment, insufficient enrichment of nanoparticles and low targeting rate, the therapeutic effect of free radicals is seriously hindered. Thus, oxygen independent radical generation strategy shows great potential. In our previous study, we demonstrated that the thermal initiator V057 could kill breast cancer cells through the photothermal effect of indocyanine green (ICG) to generate free radicals. In this project, iron doped polydiaminopyridine nanoparticles (Fe-PDAP) will be used as carriers to develop nano shuttle containing V057 and ICG encapsulated in polyethylene glycol. Depending on its fusiform structure and surface potential reversal, it can target tumor cells and mitochondria to improve tumor accumulation. At the same time, it has a certain multimodal imaging effect. It is expected to provide a new research perspective and strategy for the diagnosis and treatment of breast cancer by exploring the targeting ability of nano shuttles (NSs) and correspondence mechanism, efficacities and imaging characteristics of killing breast cancer.