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Effective transport of aggregated hypericin encapsulated in SBA-15 nanoporous silica particles for photodynamic therapy of cancer cells.
Journal of Photochemistry and Photobiology. B, Biology 2023 September 9
Photodynamic therapy (PDT) represents an interesting modality for the elimination of damaged biomaterials and cells. This treatment takes advantage of the photosensitizing properties of molecules that are active only when irradiated with light. In the present work, a dual property of hypericin, a hydrophobic molecule with high performance in photodiagnostics and photodynamic therapy, was exploited. The non-fluorescent and photodynamically inactive form of hypericin aggregates was loaded into the nanopores of SBA-15 silica particles. The synthesized particles were characterized by infrared spectroscopy, thermogravimetry, differential thermal analysis, small-angle X-ray scattering and transmission electron microscopy. Hypericin aggregates were confirmed by absorption spectra typical of aggregated hypericin and by its short fluorescence lifetime. Release of hypericin from the particles was observed toward serum proteins, mimicking physiological conditions. Temperature- and time-dependent uptake of hypericin by cancer cells showed gradual release of hypericin from the particles and active cellular transport by endocytosis. A closer examination of SBA-15-hypericin uptake by fluorescence lifetime imaging showed that aggregated hypericin molecules, characterized by a short fluorescence lifetime (∼4 ns), were still present in the SBA-15 particles upon uptake by cells. However, monomerization of hypericin in cancer cells was observed by extending the hypericin fluorescence lifetime by ∼8 ns, preferentially in lipid compartments and the plasma membrane. This suggests a promising prognosis for delayed biological activity of the entire cargo, which was confirmed by effective PDT in vitro. In summary, this work presents an approach for safe, inactive delivery of hypericin that is activated at the target site in cells and tissues.
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