Heavy-atomic construction of photosensitizer nanoparticles for enhanced photodynamic therapy of cancer

A new type of heavy-atom-affected Pluronic (F-127) nanoparticle (FIC NP) for photodynamic therapy (PDT) is reported. FIC NPs are formulated with biocompatible constituents, and contain densely integrated iodinated aromatic molecules that form a structurally rigid core matrix and stably encapsulate photosensitizers in a monomeric form. Tiny nanoparticles (∞10 nm) are prepared by aqueous dispersion of photosensitizer-embedded aromatic nanodomains, which self-assemble by phase separation from the Pluronic melt mixture. By using spectroscopic studies and cellular experiments, the following is demonstrated: 1) enhanced singlet-oxygen generation by means of the intraparticle heavy-atom effect on the embedded photosensitizer, 2) facilitated cell uptake due to the small nanoscopic size as well as the Pluronic surface characteristics, and thereby 3) actual enhancement of PDT efficacy for a human breast-cancer cell line (MDA-MB-231), which validates a photophysically motivated nanoformulation approach toward an advanced photosensitizing nanomedicine. Highly iodinated Pluronic nanoparticles stably encapsulate photosensitizers and greatly enhance singlet-oxygen generation through the intraparticle heavy-atom effect, as well as facilitate the internalization into live cancer cells. These combined merits amplify photo-induced apoptosis to afford enhanced efficacy of photodynamic therapy.