In recent years, one of main obstacles in a photodynamic therapy (PDT) process has been that most photosensitizers for PDT are excited by visible light with limited penetrating ability; thus most applications of PDT are for superficial treatments. One of the methods to increase the treatment depth is to introduce a two-photon-active technique into PDT, known as TP-PDT. The difficulty here is to obtain photosensitizers with a large enough two-photon absorption cross-section. In this work, an organic nanocomplex, composed of the two-photon nanoaggregate as the core and photosensitizer as the shell, has been constructed. Photosensitizers could be excited indirectly through a fluorescence resonance energy transfer (FRET) mechanism after the two-photon core was excited by a two-photon laser. The FRET efficiency was extremely high, owing to sufficient energy donors and stable energy acceptors. In this way, a photosensitizer could induce two-photon toxicity for improving the treatment depth in PDT. The nanocomplexes were prepared through a molecular assembly method, which avoided complicated reactions for synthesizing two-photon photosensitizers. The assembly method would expand the selection of photosensitizers and two-photon dyes, and endow traditional photosensitizers with a larger two-photon absorption cross-section for TP-PDT.
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