靶向PD-L1双模态成像引导的声动力联合治疗在三阴性乳腺癌中的研究

Triple negative breast cancer (TNBC) has an early clinical recurrence and rapid progress. Due to the lack of relevant targets and treatment options, it has become one of the research hotspots. Literature reports and the our previous studies have confirmed that targeted diagnosis based on molecular imaging and guided targeted therapy offer hope for the diagnosis and treatment of tumor diseases. Sonodynamic therapy (SDT) can not only control drug release, but also activate sonosensitizers in tumor areas by ultrasound, generate reactive oxygen species, effectively kill tumor cells, and stimulate the body's anti-tumor immune response. Combined with the immunotherapy, it is expected to enhance the anti-tumor immune effect induced by SDT. This project intends to construct an integrated probe, targeting at PD-L1 and carrying chemotherapy drugs with silicones as carriers, which have sonodynamic therapy ability and optical-magnetic resonance dual-mode imaging. It can not only reduce the premature leakage of drugs, but also actively target the aggregation of tumor areas, and stimulate the accurate release of drugs by controlling ultrasound, so as to overcome the drug resistance of tumors. At the same time, the active target is also the means of immunotherapy, so as to achieve the goal of combined treatment with a single drug delivery. Our project will provide new preclinical evidence for drug therapy and the early diagnosis of TNBC.

三阴性乳腺癌（TNBC）临床复发早、进展快，由于缺乏相应靶点，治疗选择少，因而成为研究的热点之一。文献报道及申请人前期研究证实基于分子影像的靶向诊断及其引导下的联合治疗为肿瘤疾病的诊疗带来希望。声动力治疗（SDT）不仅可以实现药物控释，还可通过超声激活肿瘤区的声敏剂，产生活性氧进而有效的杀死肿瘤细胞，并激发机体抗肿瘤的免疫反应，与免疫治疗联合，有望增强SDT激发的抗肿瘤免疫作用。本项目拟构建以PD-L1为靶点，以硅质体为载体，包载化疗药物具有声动力治疗潜能的光学-MRI诊疗一体化探针，通过双模态成像实现早期诊断及实时监测药物治疗疗效。另外，该探针不仅可以减少药物过早泄漏，还可主动靶向汇聚于肿瘤区，通过控制超声激发药物精准释放，克服药物耐药性，同时将成像靶点作为免疫治疗的手段，实现一次给药达到联合治疗的目的。有望为TNBC影像引导下的SDT联合治疗及早期诊断提供新策略。