Nanoparticle-loaded macrophage-mediated photothermal therapy: potential for glioma treatment

Abstract

Gold-based nanoparticles have been used in a number of therapeutic and diagnostic applications. The purpose of this study was to investigate the efficacy of gold–silica nanoshells (AuNS) in photothermal therapy (PTT) of rat gliomas. Rat alveolar macrophages (Ma) were used as nanoparticle delivery vectors. Uptake of AuNS (bare and PEGylated) was investigated in Ma. AuNS were incubated with Ma for 24 h. Phase contrast microscopy was used to visualize the distribution of loaded Ma in three-dimensional glioma spheroids. PTT efficacy was evaluated for both empty (Ma) and AuNS-loaded Ma (MaNS) in both monolayers and spheroids consisting of C6 rat glioma cells and Ma. Monolayers/spheroids were irradiated for 5 min with light from an 810-nm diode laser at irradiances ranging from 7 to 28 W cm−2. Monolayer survival was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay while PTT efficacy in spheroids was determined from growth kinetics and live/dead fluorescence microscopy. PTT efficacy was investigated in vivo using a Sprague–Dawley rat glioma model. Five rats received direct intracranial injection of a mixture of 104 C6 glioma cells and, 2 days later, an equal number of MaNS. Three rats received laser treatment (810 nm; 10 min; 1 W) while the remaining two served as controls (no laser treatment). The uptake ratio of bare to PEGylated AuNS by Ma was 4:1. A significant photothermal effect was observed in vitro, albeit at relatively high radiant exposures (2.1–4.2 kJ cm−2). PTT proved effective in vivo in preventing or delaying tumor development in the PTT-treated animals.

In vivo photothermal treatment by the peritumoral injection of macrophages loaded with gold nanoshells

“…Accordingly, they may preferentially penetrate into hypoxic regions within the tumor mass [14,15]. Most previous studies were confined to in vitro studies [16]. In our last study, we confirmed the possibility of using macrophages as live vectors for the delivery of nanoparticles and identified the optimal conditions for PTT to selectively kill cancer cells around nanoshell (NS)-loaded macrophages in an in vitro model [17].…”

Treatment of natural mammary gland tumors in canines and felines using gold nanorods-assisted plasmonic photothermal therapy to induce tumor apoptosis

“…21 It has been published that inflammatory tumor-associated macrophages and cancer-associated fibroblasts have high uptake toward gold NPs. [44][45][46] Our results showed complete clearance of the tumor with no relapse or metastasis. Therefore, we expect that PPTT has a significant effect on a tumor's microenvironment, which is most likely related to the high uptake of AuNRs and therefore consistent with the higher photothermal response for cancer-associated fibroblasts and inflammatory tumorassociated macrophages in the tumor microenvironment.…”

Apolipoprotein E3-mediated cellular uptake of reconstituted high-density lipoprotein bearing core 3, 10, or 17 nm hydrophobic gold nanoparticles

“…Figure S1 sPB of 3 nm auNP. UV-Vis spectrum of 3 nm auNP measured in chcl 3 . Abbreviations: auNPs, gold nanoparticles; sPB, surface plasmon band; UV-Vis, ultraviolet-visible.…”

“…1 h NMr spectra of 3 nm auNP in cDcl 3 . Abbreviations: auNPs, gold nanoparticles; NMr, nuclear magnetic resonance.…”

“…[1][2][3] Depending on the intended application, AuNPs can be functionalized with various bioconjugates, namely proteins and peptides, 4 nucleic acids, 5 and other biologically relevant molecules. 6,7 Typically, AuNP bioconjugation involves several strategies 8 such as covalent coupling to the surface ligand using reagents such as 1-ethyl-3-(3-dimethylaminopropyl)carboiimide and N-hydroxysuccinimide with biomolecules 7,9,10 or direct conjugation of biomolecules to the Au surface, often achieved by introducing reactive functional groups such as sulfhydryl groups on the side chains of the peptide and allowing the high-affinity Au-S bonding to take place.…”