基于主客体作用的超分子聚肽纳米药物构建及其性能研究

Construction and Property Research of Supramolecular Polypeptide Nanomedicine Based on Host-Guest Interactions

摘要: 吲哚菁绿(ICG)作为一种具有近红外光敏剂，被广泛应用于癌症的光热治疗。但是，由于ICG的水溶性较差，限制了其在临床上的应用。因此，我们设计并制备了末端修饰了吡啶盐的聚半胱氨酸(PPC)，其与水溶性柱[5]芳烃(WP[5])通过主客体识别作用，形成两亲性超分子聚肽。该超分子聚肽通过自组装负载ICG于内核中，形成超分子聚肽纳米药物(WPPC/ICG)。WPPC/ICG通过增强渗透与滞留(EPR)效应靶向富集在肿瘤组织部位，并经内吞作用进入肿瘤细胞后，在细胞内的酸性环境中，响应性地释放出ICG，在808 nm近红外光照射下，局部温度升高，杀死肿瘤细胞，不仅提高了疗效，而且减小了对正常组织的损伤。

Abstract: Indocyanine green (ICG) is widely used as a photosensitizer with near infrared for photothermal therapy. However, the poor water solubility of ICG limits its clinical ap-plication. Therefore, we designed and prepared polycysteine (PPC) with pyridine-terminal modifi-cation, and then formed amphiphilic supramolecular polypeptide with water-soluble pillar[5]arene based on host-guest recognition. The supramolecular polypeptide nanodrug (WPPC/ICG) was then prepared by loading ICG in the core of supramolecular polypeptide nanoassembly. WPPC/ICG could passively target and enrich in tumor tissues via enhanced osmosis and retention (EPR) effect. After entering tumor cells through endocytosis, under acidic intracellular environment, ICG could be re-sponsively released. Under 808 nm near-infrared light, the produced optothermal effect could kill tumor cells, which not only enhanced the therapeutic effect, but also reduced the damage to normal tissue.