Au-based conjugated microporous polymers for combined photodynamic and radiation therapy in cancer treatment

Abstract

Radiotherapy (RT) is a cornerstone of cancer treatment, and the radiation dose is the key factor determining its lethality. However, achieving ideal therapeutic effects requires balancing the radiation tolerance of tumor cells and the damage to surrounding healthy tissues by selecting the optimal radiation dose. Herein, we developed gold-coordinated porphyrin conjugated microporous polymers (Au-CMP) as novel radiosensitizers, aiming to achieve optimal therapeutic effects at low radiation doses. These polymers were synthesized and PEGylated to form nanoparticles (Au-CMP NPs) that enhance both photodynamic therapy (PDT) and RT by utilizing porphyrin structures for efficient singlet oxygen generation and superior radiation absorption by the high-Z element Au. In vivo studies with BEL-7402 tumor-bearing mice have confirmed that under the mediation of Au-CMP NPs, even a low dose of X-ray irradiation can exhibit significant tumor suppression effects. Furthermore, when combined with PDT, tumor proliferation is further inhibited, a finding that has also been validated in cellular experiments through increased DNA damage and reactive oxygen species generation. This research underscores the potential of Au-CMP NPs as a multifunctional, biodegradable platform to improve cancer treatment outcomes through integrated PDT and RT. The innovative approach of integrating Au-CMP NPs into cancer therapy may pave the way for more effective and less invasive treatment options, ultimately benefiting patients directly.