Over the last few decades, gold nanoparticles (GNPs) have emerged as "radiosensitizers" in oncology. Radiosensitizers are additives that can enhance the effects of radiation on biological tissues treated with radiotherapy. The interaction of photons with GNPs leads to the emission of low-energy and short-range secondary electrons, which in turn increase the dose deposited in tissues. In this context, GNPs are the subject of intensive theoretical and experimental studies aiming at optimizing the parameters leading to greater dose enhancement and highest therapeutic effect. This review describes the main mechanisms occurring between photons and GNPs that lead to dose enhancement. The outcome of theoretical simulations of the interactions between GNPs and photons is presented. Finally, the findings of the most recent in vivo studies about interactions between GNPs and photon sources (e.g., external beams, brachytherapy sources, and molecules labeled with radioisotopes) are described. The advantages and challenges inherent to each of these approaches are discussed. Future directions, providing new guidelines for the successful translation of GNPs into clinical applications, are also highlighted.

Gold Nanoparticles in Radiotherapy and Recent Progress in Nanobrachytherapy

Evaluation of size, morphology, concentration, and surface effect of gold nanoparticles on X-ray attenuation in computed tomography.

Protein-reduced gold nanoparticles mixed with gentamicin sulfate and loaded into konjac/gelatin sponge heal wounds and kill drug-resistant bacteria.

Multifunctional Chitosan-Capped Gold Nanoparticles for enhanced cancer chemo-radiotherapy: An invitro study.

Gold nanoparticles (GNPs) are proven effective heavy-atom radiosensitizers to produce imaging contrast and dose enhancement in radiotherapy. To understand the physical and biological effect of adding GNPs to the tumour cells, Monte Carlo simulation based on particle tracking and transport, is employed to predict the dosimetry in the cellular and DNA scale. In this review, we first explore the recent advances in Monte Carlo simulation on GNP radiosensitisation. The development of particle tracking algorithm for very low energy electron in the simulation is discussed, followed by some results regarding the prediction of dose enhancement (microscopic and macroscopic). We then review different Monte Carlo cell models with GNPs in the simulation, the biological effect resulting from DNA damage, and the effects of increasing imaging contrast in the tumour cell due to photoelectric enhancement. Moreover, we explain and look at different studies and results on GNP-enhanced radiotherapy using gamma rays (brachytherapy), megavoltage photon, kilovoltage photon, electron and proton beams.

Recent progress in Monte Carlo simulation on gold nanoparticle radiosensitization

Enhancing the effect of 4 MeV electron beam using gold nanoparticles in breast cancer cells

Gold nanoparticles (GNPs) have been used to sensitize cancer cells and enhance the absorbed dose delivered to such cells Active targeting can provide specific effect and higher uptake of the GNPs in the tumor cells, while having small effect on healthy cells The aim of this study was to assess the possible radiosensitiazation effect of GNPs conjugated with AS1411 aptamer (AS1411/GNPs) on cancer cells treated with 4 MeV electron beams Cytotoxicity studies of the GNPs and AS1411/GNPs were carried out with MTT and MTS assay in different cancer cell lines of MCF-7, MDA-MB-231 and mammospheres of MCF-7 cells Atomic absorption spectroscopy confirmed the cellular uptake of the gold particles Radiosensitizing effect of the GNPs and AS1411/GNPs on the cancer cells was assessed by clonogenic assay AS1411 aptamer increased the Au uptake in MCF-7 and MDA-MB-231 cells Clonogenic survival data revealed that AS1411/GNPs at 125 mg/L could result in radiosensitization of the breast cancer cells and lead to a sensitizer enhancement ratio of 135 and 166 and 191 for MCf-7, MDA-MB-231 and mammosphere cells Gold nanoparticles delivery to the cancer cells was enhanced by AS1411 aptamer and led to enhanced radiation induced cancer cells death The combination of our clonogenic assay and Au cell uptake results suggested that AS1411 aptamer has enhanced the radiation-induced cell death by increasing Au uptake This enhanced sensitization contributed to cancer stem cell-like cells to 4 MeV electron beams This is particularly important for future preclinical testing to open a new insight for the treatment of cancers

/pdf/radiosensitization-of-breast-cancer-cells-using-as1411-51w4gu31dd.pdf

Radiosensitization of breast cancer cells using AS1411 aptamer-conjugated gold nanoparticles

Introduction: A main choice for cancer treatment is radiotherapy. But, the radiotherapy disadvantage is damages caused by radiation given to normal tissues/organs surrounding cancer. One way to avoid this is via increasing radiosensitization of cancer cells. Gold nanoparticles (GNPs) have shown sensitizing effect on cancer cells by enhancing their absorbed dose. Unlike earlier delivery techniques developed for nanotherapeutics, active targeting can achieve specific effect and higher uptake of GNPs in tumors while leave healthy cells untouched and consequently improve the therapeutic index. To achieve active targeting, GNPs should be equipped with functional ligands which can recognize and adhere to the receptors of cancer cells. Aptamers are small DNA-molecule/RNA-fragments with high specificity and affinity towards target molecules. AS1411 aptamer can specifically bind to over-expressed nucleolin on the membrane of tumor cells including breast cancer. This aptamer is capable to enter cancer cells through specific ligand–receptor interaction. Greater uptake of GNPs by cells may induce increased radiation effects. Cancer stem cells are a small population of cells within a tumor capable for self-renewal and differentiation into various cell types.
Materials and Methods: We hypothesized that conjugation of GNPs with AS1411 (AS1411/GNPs) could increase GNPs-mediated radiosensitization in breast cancer cells. We hypothesized that AS1411/GNPs would radiosensitize breast cancer stem/progenitor cells grown to three- dimensional (3D) mammospheres. Cytotoxicity studies of the GNPs and AS1411/GNPs were done on two different cancer cell lines of MCF-7 and MDA-MB-231 with MTT assay. Atomic absorption spectroscopy (AAS) confirmed the cellular uptake of particles. Radiosensitizing effect of GNPs and AS1411/GNPs on MDA-MB 231 and MCF- 7 cells assessed by clonogenic assay.
Results: Clonogenic survival data revealed that AS1411/GNPs at 12.5 mg/L results in radiosensitization of breast cancer cells. Mammosphere of MCF-7 was more resistant than their monolayer counterparts.
Conclusion: The combination of the sensitizing GNPs with the AS14411 aptamer can be regarded for improved treatment of breast cancer cells especially for the mammosphere MCF-7 cancer cells mimicking cancerous tumors.

Somayeh Sadat Mehrnia

Papers

Enhancing the effect of 4 MeV electron beam using gold nanoparticles in breast cancer cells

Radiosensitization of breast cancer cells using AS1411 aptamer-conjugated gold nanoparticles

Radiosensitization of breast cancer cells using AS1411 aptamer-conjugated gold nanoparticles