A Supramolecular, Triple Negative Breast Cancer-targeting Avidin-Photosensitizer

The potential of photodynamic therapy (PDT) in combination with chemotherapy to improve treatment outcomes for triple negative breast cancer (TNBC), for which no targeted therapies are currently available, has been the subject of considerable investigation. In PDT, photosensitizers (PSs) are frequently administered directly, without the ability to selectively target cancer cells. In order to address the delivery of a PS to TNBC and enhance cellular uptake, i.e. after surgery, we prepared the Ru-NH2-modified avidin bioconjugate (RuAvi) via Tyr-specific modification using the Mannich reaction. We further assembled RuAvi to the cinnamoyl peptide-F(D)LF(D)LFK-NH2 (FK), that binds to Formyl Peptide Receptor 1, overexpressed in TNBC. Notably, the modified Avi still possesses the ability to efficiently bind biotin for assembly of up to four copies of the FK peptides and the resultant FK4-RuAvi exhibited an IC50 value of 0.36 ± 0.08 microM, which is about 3.5-fold lower than that of RuAvi (1.25 ± 0.09 microM), upon irradiation in MDA-MB-231 breast cancer cells. FK4-RuAvi also showed efficient uptake in MDA-MB-231 tumor spheroids and exhibited significant toxicity after irradiation in comparison to the control RuAvi. The presented strategy has the potential to improve the efficacy of targeted photodynamic therapy (PDT) to meet the high demand for targeted therapies to treat TNBC, for example as a targeted adjuvant treatment after breast cancer surgery.