1 research outputs found
Gold-Nanoclustered Hyaluronan Nano-Assemblies for Photothermally Maneuvered Photodynamic Tumor Ablation
Optically active nanomaterials have
shown great promise as a nanomedicine
platform for photothermal or photodynamic cancer therapies. Herein,
we report a gold-nanoclustered hyaluronan nanoassembly (GNc-HyNA)
for photothermally boosted photodynamic tumor ablation. Unlike other
supramolecular gold constructs based on gold nanoparticle building
blocks, this system utilizes the nanoassembly of amphiphilic hyaluronan
conjugates as a drug carrier for a hydrophobic photodynamic therapy
agent verteporfin, a polymeric reducing agent, and an organic nanoscaffold
upon which gold can grow. Gold nanoclusters were selectively installed
on the outer shell of the hyaluronan nanoassembly, forming a gold
shell. Given the dual protection effect by the hyaluronan self-assembly
as well as by the inorganic gold shell, verteporfin-encapsulated GNc-HyNA
(Vp-GNc-HyNA) exhibited outstanding stability in the bloodstream.
Interestingly, the fluorescence and photodynamic properties of Vp-GNc-HyNA
were considerably quenched due to the gold nanoclusters covering the
surface of the nanoassemblies; however, photothermal activation by
808 nm laser irradiation induced a significant increase in temperature,
which empowered the PDT effect of Vp-GNc-HyNA. Furthermore, fluorescence
and photodynamic effects were recovered far more rapidly in cancer
cells due to certain intracellular enzymes, particularly hyaluronidases
and glutathione. Vp-GNc-HyNA exerted a great potential to treat tumors
both <i>in vitro</i> and <i>in vivo</i>. Tumors
were completely ablated with a 100% survival rate and complete skin
regeneration over the 50 days following Vp-GNc-HyNA treatment in an
orthotopic breast tumor model. Our results suggest that photothermally
boosted photodynamic therapy using Vp-GNc-HyNA can offer a potent
therapeutic means to eradicate tumors