Photodynamic therapy (PDT) has attracted significant attention as an alternative approach to traditional cancer therapies such as radiotherapy, chemotherapy, and surgery. PDT involves irradiating a drug (the photosensitizer) with a photon of light to generate singlet oxygen (1O2) that then proceeds to kill cancer cells. Porphyrin-based photosensitizers have been widely used in PDT. Porphyrins have significant absorption in the visible region (400-700 nm), little dark toxicity, and long-lived triplet states that can lead to high singlet oxygen production. Porphyrins are known to accumulate in tumor cells in high concentrations, but aggregation, resulting from π-π stacking, often leads to a reduction in fluorescence and 1O2 quantum yields. Porphyrins are also highly hydrophobic, leading to low bioavailability and making intravenous administration difficult. Ground state curcumin analogs have been shown to have significant anti-cancer activity against various cancer lines, although these molecules have a low bioavailability due to poor absorption and fast metabolism. Four novel porphyrin-curcumin analog conjugates have been synthesized (figure 1) for use as photosensitizers in the photodynamic treatment of pancreatic ductal adenocarcinoma (PDAC) and lung cancer. Porphyrin-curcumin analog conjugates have several advantages over the individual components: (1) improvement of stability, bioavailability, and tumor site accumulation of curcumin analogs, (2) the presence of two flexibly connected chromophores that will prevent aggregation of the porphyrin component, improving both fluorescence and 1O2 quantum yields, (3) the presence of two chromophores that may maximize triplet-triplet energy transfer with 3O2 and improve 1O2 generation efficiency.

Synthesis and evaluation of Novel Porphyrin-Curcumin analog photosensitizers for photodynamic anti-cancer therapy

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.