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Temoporfin-conjugated upconversion nanoparticles for NIR-induced photodynamic therapy of pancreatic cancer
Shapoval, Oleksandr ; Větvička, D. ; Kabešová, M. ; Engstová, Hana ; Horák, Daniel
Photodynamic therapy (PDT), a clinically approved cancer treatment strategy, has the potential to cure pancreatic cancer with minimal side effects. PDT primarily uses visible wavelengths to directly activate hydrophobic photosensitizers, which may be insufficient for deep-seated cancer cells in clinical practice due to poor penetration. Upconversion nanoparticles (UCNPs) serve as an indirect excitation source to activate photosensitizers (PSs) in the NIR region, overcoming the limitations of molecular PSs such as hydrophobicity, non-specificity, and excitation in the UV/Vis region. Here, monodisperse upconversion NaYF4:Yb3+, Er3+, Fe2+ nanoparticles (UCNPs) have been surface-engineered with poly(methyl vinyl ether-alt-maleic acid) (PMVEMA) and temoporfin (mTHPC), a clinically used PDT prodrug, for near-infrared (NIR) light-triggered PDT of pancreatic cancer. The incorporation of Fe2+ ions into the particles increased the fluorescence intensity in the red region matching the activation wavelength of mTHPC. Covalent binding of mTHPC to the surface of UCNP@PMVEMA particles provided colloidally stable conjugates enabling generation of singlet oxygen. In vitro cytotoxicity and photodynamic activity of the particles were evaluated using INS-1E rat insulinoma and Capan-2 and PANC-01 human pancreatic adenocarcinoma cell lines. The PDT efficacy of UCNP@PMVEMA-mTHPC conjugates after irradiation with 980 nm NIR light was tested in vivo in a pilot study on Capan-2 human pancreatic adenocarcinoma growing subcutaneously in athymic nude mice. The intratumoral administration of the nanoconjugates significantly hindered tumor growth and demonstrated promising PDT efficacy against human pancreatic cancer.
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