Receptor-mediated DNA-targeted photoimmunotherapy.

摘要: We show the efficacy of a therapeutic strategy that combines potency DNA-binding photosensitizer, UVA Sens , with tumor-targeting potential receptor-mediated endocytosis. The photosensitizer is an iodinated bibenzimidazole, which, when bound in minor groove DNA and excited by irradiation, induces cytotoxic lesions attributed to radical species resulting from photodehalogenation. Although reminiscent photochemotherapy using psoralens established treatment modality dermatology particularly for psoriasis cutaneous T-cell lymphoma, critical difference extreme photopotency ∼1,000-fold psoralens. This feature prompted consideration combination specificity targeting. Using two vitro model systems, we cytotoxicity iodo ligand/protein conjugates, implying binding conjugate cell receptors, internalization, degradation conjugate-receptor complex, release translocation ligand nuclear DNA. For ligand-transferrin phototoxicity was inhibited coincubation excess native transferrin. Receptor-mediated UVA-induced also shown anti-human epidermal growth factor receptor monoclonal antibody, exemplifying application other cancer-specific targets thus improve phototherapy superficial extracorporeal treatments. (Cancer Res 2006; 66(21): 10548-52)