Recent advancements in tumour-targeted therapies and immunotherapy offer hope to patients with various malignancies. However, the uncontrolled growth and metastatic infiltration of malignant tumours remain a huge therapeutic challenge. Therefore, this study aimed to develop an integrated multifunctional diagnostic and treatment reagent IR-251 that can not only be used for tumour imaging but also to inhibit tumour growth and metastasis. Besides, our results showed that IR-251 targeted and damaged the mitochondria in cancer cells via organic anion-transporting polypeptides. Mechanistically, IR-251 induced ROS overproduction by inhibiting PPARγ and then inhibiting the β-catenin signalling pathway and downstream protein molecules related to the cell cycle and metastasis. Moreover, the excellent anti-tumour proliferation and metastasis ability of IR-251 were verified in vitro/in vivo. And histochemistry staining revealed that IR-251 inhibited tumour proliferation and metastasis, which showed no significant side effect. In conclusion, this novel, multifunctional, mitochondria-targeting near-infrared fluorophore probe IR-251 has great potential in achieving accurate tumour imaging and inhibiting tumour proliferation and metastasis, and the underlying mechanism of action of IR-251 is mainly via the PPARγ/ROS/β-catenin pathway.

肿瘤靶向治疗和免疫治疗的最新进展为患有各种恶性肿瘤的患者带来了希望。然而，恶性肿瘤不受控制的生长和转移性浸润仍然是巨大的治疗挑战。因此，本研究旨在开发一种一体化多功能诊断和治疗试剂IR-251，不仅可以用于肿瘤成像，还可以抑制肿瘤的生长和转移。此外，我们的结果表明IR-251通过有机阴离子转运多肽靶向并损伤癌细胞中的线粒体。从机制上讲，IR-251通过抑制PPARγ，然后抑制β-连环蛋白信号通路和与细胞周期和转移相关的下游蛋白质分子，诱导ROS过量产生。此外，IR-251优异的抗肿瘤增殖和转移能力在体外/体内得到验证。组织化学染色显示IR-251可抑制肿瘤增殖和转移，且无明显副作用。综上所述，这种新型多功能、线粒体靶向近红外荧光探针IR-251在实现肿瘤精准成像、抑制肿瘤增殖和转移方面具有巨大潜力，IR-251的作用机制主要是通过PPARγ / ROS/β-连环蛋白途径。