Hypericin–Apomyoglobin: An Enhanced Photosensitizer Complex for the Treatment of Tumor Cells

Bioavailability
of photosensitizers for cancer photodynamic therapy
is often hampered by their low solubility in water. Here, we overcome
this issue by using the water-soluble protein apomyoglobin (apoMb)
as a carrier for the photosensitizer hypericin (Hyp). The Hyp–apoMb
complex is quickly uptaken by HeLa and PC3 cells at submicromolar
concentrations. Fluorescence emission of Hyp–apoMb is exploited
to localize the cellular distribution of the photosensitizer. The
plasma membrane is rapidly and efficiently loaded, and fluorescence
is observed in the cytoplasm only at later times and to a lesser extent.
Comparison with cells loaded with Hyp alone demonstrates that the
uptake of the photosensitizer without the protein carrier is a slower,
less efficient process, that involves the whole cell structure without
preferential accumulation at the plasma membrane. Cell viability assays
demonstrate that the Hyp–apoMb exhibits superior performance
over Hyp. Similar results were obtained using tumor spheroids as three-dimensional
cell culture models.