基于Edman降解的光热纳米材料用于肿瘤靶向成像和可控药物释放

集靶向诊断和可控治疗一体化的诊疗剂对癌症的治疗至关重要。目前，诊疗剂主要是靶向肿瘤高表达水平的因子（如表面受体、酶和糖等），然而这会损伤到因子低表达水平的正常细胞。通过靶向肿瘤酸性微环境，可以提高诊疗剂的准确性。本项目基于Edman降解独特的热和酸性协同响应释放的特点，拟采用二氧化硅包裹的金纳米棒为光热载体，以Edman降解结构为骨架，将靶向配体和药物分子共价修饰在光热载体表面，构建光热可控药物释放纳米探针，用于分子影像指导下肿瘤酸性微环境的靶向成像和可控治疗。本项目创新点：第一，通过二氧化硅的共价修饰，提高了纳米材料的生物相容性、光热稳定性和释放可控性；第二，表面修饰的靶向配体有利纳米探针在肿瘤部位富集；第三，通过Edman降解甄别肿瘤酸性微环境，并实现选择性的光热可控药物释放，提高了诊疗的精准度。本项目所开发的纳米探针有望为肿瘤的定位、微创治疗和疗效的实时监测提高技术支持

The development of theranostic nanoplatforms focusing diagnostic bioimaging and therapeutic treatment are essential for cancer therapy. The theranostic nanoplatforms, based on targeting highly expressed extracellular receptors, enzymes or glucose in tumor, might damage the normal tissue which also expressed these facts. Hence, alternative approaches have recently turned to other tumor hallmark such as acidosis for improving tumor detection. Edman degradation is a common method of sequencing amino acids for peptide under the heating and acidic condition. We design and prepare the photothermally controlled nanoplatforms for bioimaging and drugs release in the acidic microenvironment of tumor based on Edman degradation. In this design, the silica coated gold nanorods improve the biocompatibility and photothermal stability. The targeted ligands modified on the surface of nanoplatforms enhance tumor accumulation. The Edman degradation selectively happened in the acidic microenvironment of tumor to improve the cancer diagnostic and therapeutic accuracy. This Edman degradation-based nanoprobe provides a new design strategy for early detection of tumor, imaging guided therapy and real-time mmonitoring curative effect.