L X-ray fluorescence cross-sections of heavy elements excited by 16.04, 16.90 and 17.78 keV photons

Vollständiger Abstract

Worum geht es in dieser Arbeit?

Although photodynamic therapy selectively eradicates tumours via light-triggered reactive oxygen species (ROS) generation, conventional photosensitizers suffer from poor solubility and a reliance on short-wavelength light with limited tissue penetration. To address this, we developed a redox-responsive polymeric nanocarrier through free-radical polymerization of a pre-assembled micellar ensemble. This ensemble formed spontaneously in aqueous solution by encapsulating the hydrophobic photosensitizer <i>meso</i>-tetrakis(<i>p</i>-hydroxyphenyl)porphyrin within a core composed of the disulfide-containing monomer <i>N</i>,<i>N</i>'-bis(acryloyl)cystamine, while a viologen-functionalized resorcinarene cavitand anchored at the micelle surface, providing colloidal stability. Polymerization yielded core-shell nanoparticles with a glutathione-cleavable, disulfide-rich core and a viologen-decorated shell. In vitro investigations across a broad panel of six malignant and two non-malignant cell lines demonstrated low dark cytotoxicity and acceptable blood compatibility, with hemolysis remaining below 10%. In the dark, the formulation induced a non-lethal, transient cytostatic effect driven by early-stage apoptosis. Crucially, upon 650 nm laser irradiation, the nanocarrier engaged powerful photodynamic activity, triggering a massive transition to late apoptosis and direct cell death, resulting in near-complete tumor cell eradication. ROS generation, subcellular localization, and programmed cell death mechanisms were confirmed by flow cytometry and fluorescence microscopy, establishing the developed redox-responsive system as an effective candidate for targeted photodynamic therapy.

Abstract: PubMed · Datensatz