Beijing National Laboratory for Molecular Sciences, Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.
University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
Adv Mater. 2024 Apr;36(14):e2310298. doi: 10.1002/adma.202310298. Epub 2024 Jan 2.
Photodynamic therapy (PDT), as a new type of light-mediated reactive oxygen species (ROS) cancer therapy, has the advantages of high therapeutic efficiency, non-resistance, and less trauma than traditional cancer therapy such as surgery, radiotherapy, and chemotherapy. However, oxygen-dependent PDT further exacerbates tumor metastasis. To this end, a strategy that circumvents tumor metastasis to improve the therapeutic efficacy of PDT is proposed. Herein, a near-infrared light-activated photosensitive polymer is synthesized and branched the anti-metastatic ruthenium complex NAMI-A on the side, which is further assembled to form nanoparticles (NP2) for breast cancer therapy. NP2 can kill tumor cells by generating ROS under 808 nm radiation (NP2 + L), reduce the expression of matrix metalloproteinases (MMP2/9) in cancer cells, decrease the invasive and migration capacity of cancer cells, and eliminate cancer cells. Further animal experiments show that NP2 + L can inhibit tumor growth and reduce liver and lung metastases. In addition, NP2 + L can activate the immune system in mice to avoid tumor recurrence. In conclusion, a PDT capable of both preventing tumor metastasis and precisely hitting the primary tumor to achieve effective treatment of highly metastatic cancers is developed.
光动力疗法(PDT)作为一种新型的光介导活性氧(ROS)癌症治疗方法,与手术、放疗和化疗等传统癌症治疗方法相比,具有治疗效率高、不易产生耐药性和创伤小的优点。然而,氧依赖性 PDT 进一步加剧了肿瘤转移。为此,提出了一种规避肿瘤转移以提高 PDT 疗效的策略。本文合成了一种近红外光激活的光敏聚合物,并在其侧链上接枝了抗转移钌配合物 NAMI-A,进一步组装成纳米颗粒(NP2)用于乳腺癌治疗。NP2 可以在 808nm 辐射下通过产生 ROS 杀死肿瘤细胞(NP2+L),降低癌细胞中基质金属蛋白酶(MMP2/9)的表达,降低癌细胞的侵袭和迁移能力,并消除癌细胞。进一步的动物实验表明,NP2+L 可以抑制肿瘤生长并减少肝和肺转移。此外,NP2+L 可以激活小鼠的免疫系统,避免肿瘤复发。总之,开发了一种既能预防肿瘤转移又能精确打击原发肿瘤的 PDT,从而有效治疗高度转移性癌症。