Hyaluronan-Metal Gold Nanoparticle Hybrids for Targeted Tumor Cell Therapy

Abstract

In this study, a novel multifunctional nanoplatform based on core-shell nanoparticles of spherical gold nanoparticles (AuNPs) capped with low and high molecular weight (200 and 700 kDa) hyaluronic acid (HA), was assembled via a green, one-pot redox synthesis method at room temperature. A multitechnique characterization approach by UV-visible spectroscopy, dynamic light scattering and atomic force microscopy pointed to the effective ‘surface decoration’ of the gold nanoparticles by HA, resulting in different grafting densities of the biopolymer chains at the surface of the metal nanoparticle, which in turn affected the physicochemical properties of the nanoparticles. Specifically, the spectral features of the gold plasmonic peak (and the related calculated optical size), the hydrodynamic diameter and the nanoparticle stability were found to depend on the molecular weight of the HA. The CD44-targeting capability of HA-functionalized gold nanoparticles was tested in terms of antibacterial activity and cytotoxicity. An enhanced inhibitory activity against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus was found, with a HA molecular weight (MW)-dependent trend for the HA-capped AuNPs compared to the bare, glucose-capped AuNPs. Cell viability assays performed on two CD44-positive cell models, namely normal human umbilical vein endothelial (HUVEC) and prostate tumor (PC-3) cells, in comparison with neuroblastoma cells (SH-SY5Y), which do not express the CD44 receptor, demonstrated an increased cytotoxicity in neuroblastoma compared to prostate cancer cells upon the cellular treatments by HA–AuNP compared to the bare AuNP, but a receptor-dependent perturbation effect on cytoskeleton actin and lysosomal organelles, as detected by confocal microscopy. These results highlighted the promising potentialities of the HA-decorated gold nanoparticles for selective cytotoxicity in cancer therapy. Confocal microscopy imaging of the two human tumor cell models demonstrated a membrane-confined uptake of HA-capped AuNP in the cancer cells that express CD44 receptors and the different perturbation effects related to molecular weight of HA wrapping the metallic core of the plasmonic nanoparticles on cellular organelles and membrane mobility.

Functionalized Gold Nanoparticles: Synthesis, Properties and Biomedical Applications

“…Thus, HA‐AuNP was more cytotoxic to neuroblastoma cells than prostate cancer cells, but HA‐AuNP had receptor‐dependent perturbations on cytoskeleton actin and lysosomal organelles. These results highlight the potential of HA modified AuNPs for selective cytotoxicity in tumor treatment and the potential to regulate anti‐angiogenic effects by controlling cell migration during tumor metastasis [63] …”

“…These results highlight the potential of HA modified AuNPs for selective cytotoxicity in tumor treatment and the potential to regulate anti-angiogenic effects by controlling cell migration during tumor metastasis. [63] Yang et al proposed a tapered fiber optic glucose sensor synthesized by GO and AuNPs. Figure 26 is a schematic diagram of the sensor.…”

“…The intensity and wavelength of . [63] Reprinted with permission from [63]. Copyright 2020 MDPI, Switzerland.…”

Co-delivery of Salinomycin and Curcumin for Cancer Stem Cell Treatment by Inhibition of Cell Proliferation, Cell Cycle Arrest, and Epithelial–Mesenchymal Transition

“…Salinomycin and curcumin were loaded onto poly(lactic-co-glycolic acid) (PLGA) polymeric nanoparticles via double emulsion method to form nanoparticles (Avgoustakis et al, 2002 ; Alam et al, 2017 ). Additionally, hyaluronic acid (HA) was also conjugated to nanoparticles as targeting moiety due to its specific interaction with the CD44 receptor, which is a cell surface glycoprotein and commonly overexpressed on BCSCs (Zöller, 2011 ; Ganesh et al, 2013 ; Sanfilippo et al, 2020 ). The CD44-targeting nanoparticles loaded with salinomycin and curcumin showed improved therapeutic efficiency against BCSCs by inducing G 1 cell cycle arrest and limiting epithelial–mesenchymal transition (EMT).…”

Gold Nanoparticles Functionalized with Angiogenin for Wound Care Application

“…This phenomenon is termed surface plasmon resonance (SPR) and allows for the application of the nanoparticles as biosensors and theranostic systems [ 34 , 35 , 36 ]. Noteworthy, the change in the optical plasmonic features of metal nanoparticles upon the immobilization of a biomolecule at their surface can be very useful to discriminate among different biomolecule conformations at the interface with the metal [ 37 , 38 , 39 ].…”