Liu Xiao, Zheng Hongwei, Peng Yiqian, Ji Dongliang, Wang Chen, Wang Dezhi, Jia Zihan, Chang Yingxue, Cai Xiangming, Wang Lei, Ling Yong
School of Pharmacy, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu Province, China.
School of Medical, Nantong University, Nantong 226001, Jiangsu Province, China.
Mol Pharm. 2025 Feb 3;22(2):882-894. doi: 10.1021/acs.molpharmaceut.4c01046. Epub 2025 Jan 4.
Photodynamic therapy (PDT) is increasingly regarded as an attractive approach for cancer treatment due to its advantages of low invasiveness, minimal side effects, and high efficiency. Here, two novel Ru(II) complexes , were designed and synthesized by coordinating phenanthroline and biquinoline ligands with Ru(II) center, and their chemo-photodynamic therapy and immunotherapy were explored. Both and exhibited significant phototoxicity against A549 and 4T1 tumor cells type-I/-II PDT. Among them, exhibited superior oxygen-independent antitumor effects (ICs = 1.50-1.76 μM) upon laser irradiation, and displayed micromolar-level chemotherapeutic activities, indicating its potential for chemo/photodynamic dual effects. Furthermore, also initiated an ICD cascade, enhancing recruitment and maturation of antigen-presenting cells, thus triggering a CD8 T cell antitumor immune response. Finally, antitumor experiments demonstrated that exhibited significant inhibition of lung and breast tumor growth, with inhibition rates of 94.6% and 97.3%, respectively. Therefore, the Ru(II) complexes we designed, as effective type-I/-II photosensitizers and potential immunoactivators, demonstrate multiple antitumor mechanisms, warranting further study.
光动力疗法（PDT）因其具有低侵袭性、最小副作用和高效率等优点，越来越被视为一种有吸引力的癌症治疗方法。在此，通过将菲咯啉和联喹啉配体与Ru（II）中心配位，设计并合成了两种新型Ru（II）配合物，并对其化学-光动力疗法和免疫疗法进行了探索。 和 对A549和4T1肿瘤细胞均表现出显著的I型/II型光毒性。其中， 在激光照射下表现出优异的不依赖氧的抗肿瘤作用（IC50 = 1.50 - 1.76 μM），并显示出微摩尔水平的化疗活性，表明其具有化学/光动力双重作用的潜力。此外， 还引发了免疫原性细胞死亡（ICD）级联反应，增强了抗原呈递细胞的募集和成熟，从而触发了CD8 + T细胞抗肿瘤免疫反应。最后， 抗肿瘤实验表明， 对肺癌和乳腺癌的生长具有显著抑制作用，抑制率分别为94.6%和97.3%。因此，我们设计的Ru（II）配合物作为有效的I型/II型光敏剂和潜在的免疫激活剂，展示了多种抗肿瘤机制，值得进一步研究。
