Gold-Nanoclustered Hyaluronan Nano-Assemblies for Photothermally Maneuvered Photodynamic Tumor Ablation

Abstract

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 in vitro and in vivo. 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.

Hyaluronic Acid–Based Activatable Nanomaterials for Stimuli‐Responsive Imaging and Therapeutics: Beyond CD44‐Mediated Drug Delivery

“…In addition to chemotherapy, HA‐based nanomaterials are useful for targeted photodynamic therapy and/or photothermal therapy. Recently, researchers reported biostable, photoactivatable hybrid nanomaterials based on a gold‐nanoclustered HA nanoassembly (GNc‐HyNA) for photothermally boosted photodynamic tumor ablation ( Figure ) …”

“…The error bars represent the standard deviations of five mice per group. Adapted with permission . Copyright 2016, American Chemical Society.…”

“…Recently, the ability of nanomaterials to respond actively to local microenvironments, to enable spatial and temporal functions, has emerged as a promising strategy for diagnostic and therapeutic delivery . These nanocarriers can change their molecular structure, solubility, surface characteristics, shape, and self‐association or dissociation behaviors in response to endogenous stimuli such as pH changes, different levels of enzymes, cellular traction forces, reactive oxygen species (ROS), or glutathione in diseased tissues or in intracellular compartments. Also, they can respond to exogenous stimuli, such as laser irradiation or temperature changes, to generate an off/on activation of imaging or therapeutic function.…”

Nanotechnology‐Mediated Drug Delivery for the Treatment of Obesity and Its Related Comorbidities

“…HA‐NPs were shown to display great biocompatibility and receptor‐binding properties, and HA self‐assembles into nanocarriers for hydrophobic drug delivery . Interestingly, Rho et al showed that HA‐NPs without encapsulated therapeutics accumulated in adipose tissue of diet‐induced obesity mice, inhibit low molecular weight (LMW) HA binding to CD44, and decrease LMW HA‐induced proinflammatory signaling through induction of CD44 clustering, leading to the normalization of blood glucose levels and insulin sensitivity in obese mice ( Figure ) .…”

Metal-Phenolic Network-Coated Hyaluronic Acid Nanoparticles for pH-Responsive Drug Delivery

“…HACA was prepared using EDC/NHS chemistry. For this chemistry, the amine derivative of CA was prepared as previously reported [31][32][33]. Then, the aminated CA was chemically conjugated to the HA backbone.…”