A novel targeted conjugate for photodynamic therapy of HER2-positive cancer

Low selectivity against cancer cells remains one of the key challenges of many modern photosensitizers. To enhance the selectivity of the action and the effectiveness of tumor therapy, a conjugate was developed comprising a photoactive compound, the water-soluble silicon phthalocyanine complex (IR700, IRDye 700DX NHS ester), and the targeted molecule DARPin G3-ABD, which is designed to target human epidermal growth factor receptor type 2 (HER2). The phototoxicity of the individual substance IR700 and the DARPin G3-ABD-IR700 conjugate was tried on tumor cell cultures with different HER2 expression levels (SKBR-3, SKOV-3, BT-474, and PC-3). The cells were irradiated using LED diodes with a wavelength of 690 nm and a luminous flux density of 0.5 W/cm2. Cell viability after irradiation and following all the experimental procedures was evaluated using the standard MTT assay. The developed conjugate proved to specifically bind to HER2 receptors. The combination of high photosensitizing activity and selectivity of action against tumor cells makes the DARPin G3-ABD-IR700 conjugate a promising targeted agent for photodynamic therapy.