携载CRISPR-Cas13a 生物合成囊泡在乳腺癌诊疗一体化中的实验研究

乳腺癌是全球范围内女性最常见的恶性肿瘤。研究表明，某些浮游微生物产生的气体囊泡可用于超声造影剂。癌基因MicroRNA-155 (miR-155) 在包括乳腺癌在内的许多癌症中都存在着过表达，可以作为乳腺癌治疗的靶点。CRISPR-Cas13a 可以靶向敲除哺乳动物细胞中 RNA。本研究拟利用iRGD 修饰来源于嗜盐古菌、蓝藻等浮游微生物的气体囊泡，制成靶向纳米超声造影剂，对乳腺癌进行精准显像，同时表面用PEI将其修饰成阳离子囊泡，靶向递送可以沉默miR-155的CRISPR–Cas13a 至肿瘤部位，联合超声靶向微泡爆破技术实现CRISPR–Cas13a的定向控释来精准治疗乳腺癌，以期为乳腺癌患者的诊疗一体化研究提供新的思路。

Breast cancer is the most common malignancy in women worldwide. Evidences demonstrated gas vesicles produced by some floated microorganisms can be served as ultrasound contrast agents. MicroRNA-155 (miR-155), a well-known oncogenic microRNA, is overexpressed in many human cancers including breast cancer, and could be used as a target for the treatment of breast cancer. CRISPR-Cas13a can be engineered for mammalian cell RNA knockdown. In this study, we use iRGD to modify the gas vesicles produced by some floated microorganisms such as halophilic archaea and cyanobacteria to produce targeted nano-ultrasound contrast agent for accurate imaging of breast cancer. Meanwhile, cationic vesicles were modified by polyethylenimine (PEI) to form cationic vesicles, which can target delivery CRISPR-Cas13a to the tumor site. Combined with ultrasound targeted microbubble blasting technology, the nano-system can realize directional controlled release of CRISPR-Cas13a. Our study will provide a novel idea to for the integrated research of diagnosis and treatment of breast cancer patients.