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

Adv Mater. 2024 Apr;36(14):e2310298. doi: 10.1002/adma.202310298. Epub 2024 Jan 2.

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.

Keywords: ROS responsive polymer; anti‐metastasis; localization; matrix metalloproteinases (MMP2/9); photodynamic therapy; ruthenium complexes NAMI‐A; tumor metastasis.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Dimethyl Sulfoxide / analogs & derivatives*
  • Mice
  • Nanoparticles* / therapeutic use
  • Neoplasm Recurrence, Local / drug therapy
  • Organometallic Compounds*
  • Photochemotherapy*
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Polymers
  • Reactive Oxygen Species / metabolism
  • Ruthenium Compounds*

Substances

  • imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III)
  • Reactive Oxygen Species
  • Polymers
  • Photosensitizing Agents
  • Dimethyl Sulfoxide
  • Organometallic Compounds
  • Ruthenium Compounds