Abstract
Poly(ethylene glycol)-b-poly(caprolactone) (PEG-b-PCL) micelles dually loaded with both pheophorbide a (PhA) as a photosensitizer and β-carotene (CAR) as a singlet oxygen (1O2) scavenger were designed to control photodynamic therapy (PDT) activity in cancer treatment. The CAR in the PhA/CAR micelles significantly diminished PhA-generated 1O2 through direct 1O2 scavenging, whereas the CAR molecules lost their 1O2 scavenging activity when the PhA and CAR were spatially isolated by the disintegration of the PEG-b-PCL micelles. In cell-culture systems, light irradiation at a post-treatment time that corresponded to the presence of the micelles in the blood environment induced negligible phototoxicity, whereas light irradiation at a post-treatment time that corresponded to the presence of the micelles in the intracellular environment induced remarkable phototoxicity. In addition, a longer post-treatment time induced greater internalization of PhA/CAR micelles, which resulted in higher phototoxicity, suggesting an increase in photo killing activity against the tumor cells of interest. Thus, the co-loading of a 1O2 generator and a 1O2 scavenger into a single micelle is a potential strategy that may be useful in facilitating more accurate and reliable PDT with site-specific controllable production of singlet oxygen species for cancer treatment.
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