2 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
Intracellularly Activatable Nanovasodilators To Enhance Passive Cancer Targeting Regime
Conventional cancer targeting with
nanoparticles has been based
on the assumed enhanced permeability and retention (EPR) effect. The
data obtained in clinical trials to date, however, have rarely supported
the presence of such an effect. To address this challenge, we formulated
intracellular nitric oxide-generating nanoparticles (NO-NPs) for the
tumor site-specific delivery of NO, a well-known vasodilator, with
the intention of boosting EPR. These nanoparticles are self-assembled
under aqueous conditions from amphiphilic copolymers of polyÂ(ethylene
glycol) and nitrated dextran, which possesses inherent NO release
properties in the reductive environment of cancer cells. After systemic
administration of the NO-NPs, we quantitatively assessed and visualized
increased tumor blood flow as well as enhanced vascular permeability
than could be achieved without NO. Additionally, we prepared doxorubicin
(DOX)-encapsulated NO-NPs and demonstrated consequential improvement
in therapeutic efficacy over the control groups with considerably
improved DOX intratumoral accumulation. Overall, this proof of concept
study implies a high potency of the NO-NPs as an EPR enhancer to achieve
better clinical outcomes