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 therapy is available, is the subject of considerable investigation. In PDT, photosensitizers (PSs) are frequently administered directly but do not selectively target cancer cells. To address the delivery of a PS to TNBC and enhance cellular uptake, the Ru-NH₂-modified avidin bioconjugate (^RuAvi) via Tyr-specific modification using the Mannich reaction is prepared. The ^RuAvi is further assembled with the cinnamoyl peptide-F(D)LF(D)LFK-NH₂ (FK), which binds to formyl peptide receptor 1, overexpressed in TNBC. Notably, the modified Avi still possesses the ability to efficiently bind biotin for the assembly of up to four copies of the FK peptides. The resultant FK₄-^RuAvi exhibited an IC₅₀ value of 0.36 ± 0.08 µM, which is ≈3.5-fold lower than that of ^RuAvi (1.25 ± 0.09 µM), upon irradiation in the triple-negative MDA-MB-231 breast cancer cells. FK₄-^RuAvi also shows efficient uptake in MDA-MB-231 tumor spheroids and exhibited significant toxicity after irradiation compared to the control ^RuAvi. The presented strategy has the potential to improve the efficacy of targeted PDT to meet the high demand for targeted therapies to treat TNBC, such as targeted adjuvant treatment after breast cancer surgery.