Localization of Cancer Cells for Subsequent Robust Photodynamic Therapy by ROS Responsive Polymeric Nanoparticles With Anti‐Metastasis Complexes NAMI‐A

Abstract 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.