Antibody-guided iodinated cyanine for near-IR photoimmunotherapy

Photoimmunotherapy (PIT) is a cancer treatment modality that synergistically combines immunotherapy and photodynamic treatment (PDT). Many current photosensitizers used in PDT and PIT applications such as porphyrins suffer from insufficient light absorption in the near-IR spectra region, which reduces their phototoxicity. Cyanine dyes exhibit much more pronounced absorption in the near-IR region but they are less explored for PDT and their antibody-guided conjugates have not yet been studied for PIT applications. In this work, for the first time a “cyanine dye — antibody” PIT conjugate is developed and studied. We synthesized novel, highly water soluble, near-IR, diiodinated heptamethine cyanine dye, 2ICy7, conjugated this dye with the breast cancer-specific monoclonal antibody trastuzumab, and investigated the obtained PIT conjugate in the mouse xenograft model to suppress tumor growth versus the parent, non-iodinated Cy7–Ab conjugate. The quantum yields of the singlet oxygen generation in aqueous media for the iodinated 2ICy7 dye and 2ICy7–Ab conjugate were found to be about 3-fold higher compared to the non-iodinated counterparts, Cy7 and Cy7–Ab. As a result, the 2ICy7–Ab conjugate suppressed tumor growth upon PIT four-fold more efficiently than Cy7–Ab, while the immunotherapeutic effect resulted only in 1.4-fold suppression.