Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Science, China Three Gorges University, Yichang 443002, China.
The First College of Clinical Medical Science, China Three Gorges University, Yichang 443003, China.
Molecules. 2024 Sep 9;29(17):4277. doi: 10.3390/molecules29174277.
Polyamines play a pivotal role in cancer cell proliferation. The excessive polyamine requirement of these malignancies is satisfied through heightened biosynthesis and augmented extracellular uptake via the polyamine transport system (PTS) present on the cell membrane. Meanwhile, photodynamic therapy (PDT) emerges as an effective anti-cancer treatment devoid of drug resistance. Recognizing these intricacies, our study devised a novel polyamine-derived photosensitizer (PS) for targeted photodynamic treatment, focusing predominantly on pancreatic cancer cells. We synthesized and evaluated novel spermine-derived fluorescent probes (N2) and PS (N3), exhibiting selectivity towards pancreatic cancer cells via PTS. N3 showed minimal dark toxicity but significant phototoxicity upon irradiation, effectively causing cell death in vitro. A significant reduction in tumor volume was observed post-treatment with no pronounced dark toxicity using the pancreatic cancer CDX mouse model, affirming the therapeutic potential of N3. Overall, our findings introduce a promising new strategy for cancer treatment, highlighting the potential of polyamine-derived PSs in PDT.
多胺在癌细胞增殖中发挥关键作用。这些恶性肿瘤对多胺的过度需求通过提高生物合成和通过细胞膜上的多胺转运系统 (PTS) 增加细胞外摄取来满足。同时，光动力疗法 (PDT) 作为一种有效的抗癌治疗方法，没有耐药性。认识到这些复杂性，我们的研究设计了一种新型的多胺衍生的光敏剂 (PS) 用于靶向光动力治疗，主要针对胰腺癌细胞。我们合成并评估了新型精脒衍生的荧光探针 (N2) 和 PS (N3)，通过 PTS 对胰腺癌细胞表现出选择性。N3 在照射下表现出最小的暗毒性但显著的光毒性，有效导致体外细胞死亡。在使用胰腺癌 CDX 小鼠模型进行治疗后，观察到肿瘤体积显著减少，且无明显暗毒性，证实了 N3 的治疗潜力。总的来说，我们的研究结果为癌症治疗提出了一种有前途的新策略，强调了多胺衍生 PS 在 PDT 中的潜力。
