IMMOBILIZATION OF BIOLOGIC PHOTOSENSITIZER CONJUGATES ON NANOPARTICLES TO ENHANCE PHOTOIMMUNOTHERAPY EFFICACY

摘要

Light-activatable immunoconjugates have recently shown promise for photoimmunotherapy and fluorescence-guided resection in patients suffering from incurable malignancies in early clinical trials. While possessing a number of unique advantages, photoimmunotherapy and fluorescence imaging for oncological diseases can be hampered by therapeutic inefficiency resulting from inadequate photosensitizer delivery. The study suggests that successful coupling of antibody-photosensitizer photoimmunoconjugates onto polymeric nanoparticles complements the promising attributes of simple photoimmunoconjugates in two significant ways: Not only does it improve photosensitizer delivery to tumor, but also offers a forward-looking opportunity to deliver significant and diverse second agents, which can be an imaging agent or a different therapeutic agent, to further enhance the theranostic benefits of photoimmunoconjugates. This approach, based on nanoparticle engineering, achieves effective photoimmunoconjugate delivery and enhances the anti-tumor efficacy in two EGFR-overexpressing cancer cell lines in vitro and in a xenograft tumor mouse model. Furthermore, the selectivity, photochemical and photophysical characteristics (e.g. absorbance, fluorescence quenching, and singlet oxygen yield) of the photoimmunoconjugated nanoplatform were thoroughly investigated. This next generation photoimmunoconjugate-nanoparticle delivery approach offers a unique opportunity to monitor disease, destroy cancer cells and co-deliver a follow-up treatment more efficiently, and thus merits further investigations in preclinical and clinical settings.