Combining Augmented Radiotherapy and Immunotherapy through a Nano-Gold and Bacterial Outer-Membrane Vesicle Complex for the Treatment of Glioblastoma

Abstract

Glioblastoma, formerly known as glioblastoma multiforme (GBM), is refractory to existing adjuvant chemotherapy and radiotherapy. We successfully synthesized a complex, Au–OMV, with two specific nanoparticles: gold nanoparticles (AuNPs) and outer-membrane vesicles (OMVs) from E. coli. Au–OMV, when combined with radiotherapy, produced radiosensitizing and immuno-modulatory effects that successfully suppressed tumor growth in both subcutaneous G261 tumor-bearing and in situ (brain) tumor-bearing C57BL/6 mice. Longer survival was also noted with in situ tumor-bearing mice treated with Au–OMV and radiotherapy. The mechanisms for the successful treatment were evaluated. Intracellular reactive oxygen species (ROS) greatly increased in response to Au–OMV in combination with radiotherapy in G261 glioma cells. Furthermore, with a co-culture of G261 glioma cells and RAW 264.7 macrophages, we found that GL261 cell viability was related to chemotaxis of macrophages and TNF-α production.

Pharmacological Role of Functionalized Gold Nanoparticles in Disease Applications

“…Gold nanoparticles with outer membrane vesicles from E. coli (Au-OMV) (at concentrations of 200 μg mL −1 and 2 μg mL −1 for Au and OMV, respectively) combined with radiotherapy produce radiosensitization and immunomodulatory effects, and successfully inhibit tumor growth in both subcutaneous GL261 glioma cells tumor-bearing and in situ (brain) tumor-bearing C57BL/6 mice. In GL261 glioma cells, Au-OMV combined with radiotherapy greatly increases intracellular reactive oxygen species (ROS) [ 41 ]. Recent experimental results have shown that chitosan-capped gold nanoparticle-loaded doxorubicin (CS-GNPs-DOX, 25 nm; 0.1 mM Au concentration) can enhance the effect of radiotherapy and chemotherapy by increasing DNA double-strand breaks and inducing cell necrosis, to significantly reduce the viability of cancer cells, even at very low radiation doses (0.5-Gray, Gy).…”

Bacterial extracellular vesicles as bioactive nanocarriers for drug delivery: Advances and perspectives

“…Due to this natural penetration ability, BEVs are valued as potential players in intracranial delivery. Nanogold and bacterial vesicle hybrid particles were introduced by Chen et al [ 135 ] to augment chemoradiotherapy against glioblastoma and achieve longer survival of experimental mice. 4CMenB (Bexsero; GSK Biologicals), a vaccine against Neisseria meningitidis serogroup B (MenB), was introduced in 2013 and was confirmed to protect infants and children from MenB [ 136 ].…”

Potential targets and treatments affect oxidative stress in gliomas: An overview of molecular mechanisms

“…Outer-membrane vesicles (OMVs) from Escherichia coli and gold nanoparticles (AuNPs) were combined to synthesize Au-OMVs. Combining Au-OMVs with radiotherapy generated ROS to increase radiosensitization and suppress glioma cell growth (Chen et al, 2021). Proton beam radiation generates substantial amounts of ROS, which induces cell cycle redistribution and DNA damage and promotes apoptosis in GSCs (Alan Mitteer et al, 2015).…”