Gold nanoparticles, radiations and the immune system: Current insights into the physical mechanisms and the biological interactions of this new alliance towards cancer therapy

Abstract

Considering both cancer's serious impact on public health and the side effects of cancer treatments, strategies towards targeted cancer therapy have lately gained considerable interest. Employment of gold nanoparticles (GNPs), in combination with ionizing and non-ionizing radiations, has been shown to improve the effect of radiation treatment significantly. GNPs, as high-Z particles, possess the ability to absorb ionizing radiation and enhance the deposited dose within the targeted tumors. Furthermore, they can convert non-ionizing radiation into heat, due to plasmon resonance, leading to hyperthermic damage to cancer cells. These observations, also supported by experimental evidence both in vitro and in vivo systems, reveal the capacity of GNPs to act as radiosensitizers for different types of radiation. In addition, they can be chemically modified to selectively target tumors, which renders them suitable for future cancer treatment therapies. Herein, a current review of the latest data on the physical properties of GNPs and their effects on GNP circulation time, biodistribution and clearance, as well as their interactions with plasma proteins and the immune system, is presented. Emphasis is also given with an in depth discussion on the underlying physical and biological mechanisms of radiosensitization. Furthermore, simulation data are provided on the use of GNPs in photothermal therapy upon non-ionizing laser irradiation treatment. Finally, the results obtained from the application of GNPs at clinical trials and pre-clinical experiments in vivo are reported.

Cellular Uptake and Radio-sensitization Effect of Small Gold Nanoparticles in MCF-7 Breast Cancer Cells

“…Translocation of AuNPs across the cell membrane can be achieved via passive translocation or active endocytosis [33], the later resulting in endosomal/lysosomal AuNP intracellular processing [34,35]. Nanoparticles smaller than 10 nm are more likely to be taken up by passive process, while the receptor mediated endocytic pathway is typical for the larger ones and is associated with a better cellular uptake [33,36]. Once inside the cells AuNPs are trapped inside the endo-and lysosomal vesicles with no free AuNPs within the cytosol or nucleus [34,37].…”

“…In addition, all these variables can also profoundly affect AuNPs biodistribution and biocompatibility and have been studied by different investigators, often reporting inconclusive and controversial results. Larger size AuNPs, have been reported to be less efficient in penetrating and evenly distributing within the tumor tissue and are more readily captured by macrophages and accumulated in liver [36,40]. On the other hand, AuNPs smaller than 5 nm in size tend to be rapidly eliminated through kidneys [41] and are more toxic at the cellular level [42,43].…”

Latest advances in combining gold nanomaterials with physical stimuli towards new responsive therapeutic and diagnostic strategies

“…Such electrons cause cell damage by direct interaction ("physical enhancement"), production of free radicals ("chemical enhancement"), and/or production of ROS and oxidative stress ("biological enhancement"). Detailed reviews describing the radiosensitization mechanisms triggered by AuNMs have recently published [70][71][72]; whereas, Cole et al have discussed the nanomaterial optimized properties, such as composition, mass concentration, size, shape and surface functionalization, that ensure AuNM optimal functional performance as contrast agents in X-ray imaging and computed tomography [73].…”

Long Exposure to CdS-Dextrin Nanoparticles Induces an Immunomodulatory and Anti-Inflammatory Effect in Rats

“…Nanomaterials by themselves are foreign substances and should be able to trigger an immune response; that said, whether they go unnoticed or interact directly is still debatable. The extant literature shows nanomaterials can exert both favorable and harmful effects on the organism as a result of their interaction with the immune system, and this will basically depend on the properties and coating of nanoparticles [24][25][26][27].…”