Synthesis and Biological Properties of EGFR-Targeted Photosensitizer Based on Cationic Porphyrin.
Yulia S BortnevskayaNikita A ShiryaevNikita S ZakharovOleg O KitoroageMargarita A GradovaNatalia Yu KarpechenkoKonstantin Yu ZhizhinElena D NikolskayaMariia R MollaevaNikita G YabbarovNatal'ya A BraginaKseniya A ZhdanovaPublished in: Pharmaceutics (2023)
Photodynamic therapy (PDT) in oncology is characterized by low invasiveness, minimal side effects, and little tissue scarring. Increasing the selectivity of PDT agents toward a cellular target is a new approach intended to improve this method. This study is devoted to the design and synthesis of a new conjugate based on meso-arylporphyrin with a low-molecular-weight tyrosine kinase inhibitor, Erlotinib. A nano-formulation based on Pluronic F127 micelles was obtained and characterized. The photophysical and photochemical properties and biological activity of the studied compounds and their nano-formulation were studied. A significant, 20-40-fold difference between the dark and photoinduced activity was achieved for the conjugate nanomicelles. After irradiation, the studied conjugate nanomicelles were 1.8 times more toxic toward the EGFR-overexpressing cell line MDA-MB-231 compared to the conditionally normal NKE cells. The IC50 was 0.073 ± 0.014 μM for the MDA-MB-231 cell line and 0.13 ± 0.018 μM for NKE cells after irradiation for the target conjugate nanomicelles.
Keyphrases
- photodynamic therapy
- cancer therapy
- cell cycle arrest
- drug delivery
- induced apoptosis
- epidermal growth factor receptor
- small cell lung cancer
- fluorescence imaging
- cell death
- tyrosine kinase
- palliative care
- pi k akt
- breast cancer cells
- solid state
- endoplasmic reticulum stress
- radiation therapy
- signaling pathway
- quantum dots
- electron transfer
- drug release