Improved photodynamic therapy of hepatocellular carcinoma via surface-modified protein nanoparticles
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MDPI
Abstract
Background: Photodynamic therapy (PDT) has evolved as a reliable therapeutic
modality for cancer. However, the broad application of the technique is still limited because
of poor bioavailability and the non-selective distribution of photosensitizers within host tissues. Herein, zein, a natural corn protein, was functionalized with glycyrrhetinic acid (GA)
and polyethylene glycol (Z-PEG-GA) as a targeting platform for liver cancer cells. Parietin,
as novel photosensitizer, was successfully encapsulated into zein via nanoprecipitation and
used for the therapy of hepatocellular carcinoma. Methods: The in vitro phototoxicity of ZPEG-GA nanoparticles and their non-functionalized control (Z-PEG) were assessed against
hepatocellular carcinoma (HepG2 cells) and the In vivo biodistribution was determined
in an adult male CD-1 Swiss albino mice model. Results: The formulated Z-PEG and
Z-PEG-GA showed spherical shapes with average sizes of 82.8 and 94.7 nm for unloaded
nanoparticles, respectively, and 109.7 and 111.5 nm for loaded nanoparticles carrying more
than 70% of parietin, and Quantum yield measurements show that parietin’s photodynamic
potential is conserved. Moreover, parietin-loaded Z-PEG-GA exhibited three-fold higher
toxicity against liver cancer cells than its non-functionalized control and attained more
than an eleven-fold enhancement in the generated intracellular reactive oxygen species
(ROS) at a 9 J/cm2
radiant exposure. The generated intracellular ROS led to mitochondrial
disruption and the release of cytochrome c. In vivo biodistribution studies revealed that
fluorescence signals of Z-PEG-GA can persist in the excised animal liver for up to 24 h
post-administration. Conclusions: Consequently, tailored zein can hold great potential for
delivering several hydrophobic photosensitizers in anticancer PDT.
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Except where otherwised noted, this item's license is described as Attribution 4.0 International