“K-cell targeted photodynamic therapy (K-cell targeted PDT)” with a minimally invasive procedure was investigated to reduce the secretion of gastric inhibitory polypeptide (GIP), an incretin hormone secreted from enteroendocrine K-cells in the duodenum that is suspected to be strongly correlated with obesity. Oleic acid-poly (ethylene glycol)-chlorin e6 (OA-PEG-Ce6, OPC) was designed for PDT because it targets K-cells through the interaction of OA in OPC with a G protein-coupled receptor (GPR 119) that is overexpressed on K-cells and mediates fatty acid sensing. OPC interacted with duodenal cells (HUTU-80) expressing GPR 119 and HEK 293 cells transfected with human GPR 119 to mimic K-cells in vitro. The intracellular intensity and cytotoxicity of OPC on HUTU-80 cells increased 5- and 3-fold compared to PEG-Ce6, respectively. In particular, its intensity on HEK 293 cells overexpressing GPR 119 showed 7.8-fold higher than that of PEG-Ce6. Moreover, in high fat-diet animal models, OPC induced endocrine cell death through PDT, resulting in a decrease in the plasma GIP level and a reduction their weight (80% less than on the day of PDT initiation). Therefore, K-cell targeted PDT presents a new direction of future minimally invasive anti-obesity treatment to replace conventional methods such as bariatric surgery and radiofrequency ablation.

研究了采用微创程序的“ K细胞靶向光动力疗法（K细胞靶向PDT）”，以减少胃抑制性多肽（GIP）的分泌，GIP是十二指肠肠内分泌K细胞分泌的肠降血糖素，被怀疑是与肥胖密切相关。油酸-聚（乙二醇）-二氢卟酚e6（OA-PEG-Ce6，OPC）是为PDT设计的，因为它通过OPC中的OA与G蛋白偶联受体（GPR 119）的相互作用靶向K细胞。在K细胞上过度表达并介导脂肪酸感应。OPC与表达GPR 119的十二指肠细胞（HUTU-80）相互作用以及用人GPR 119转染的HEK 293细胞在体外模拟K细胞。与PEG-Ce6相比，OPC对HUTU-80细胞的细胞内强度和细胞毒性分别增加了5倍和3倍。特别是，它在过表达GPR 119的HEK 293细胞上的强度比PEG-Ce6高7.8倍。此外，在高脂饮食动物模型中，OPC会通过PDT诱导内分泌细胞死亡，从而导致血浆GIP水平降低并减轻其重量（比PDT启动当天减少80％）。因此，以K细胞为靶标的PDT为未来的微创抗肥胖疗法提出了新的方向，以取代常规方法，例如减肥手术和射频消融。