Imaging intracellular and systemicin vivogold nanoparticles to enhance radiotherapy

Abstract

Nanoparticles offer alternative options in cancer therapy both as drug delivery carriers and as direct therapeutic agents for cancer cell inactivation. More recently, gold nanoparticles (AuNPs) have emerged as promising radiosensitizers achieving significantly elevated radiation dose enhancement factors when irradiated with both kilo-electron-volt and mega-electron-volt X-rays. Use of AuNPs in radiobiology is now being intensely driven by the desire to achieve precise energy deposition in tumours. As a consequence, there is a growing demand for efficient and simple techniques for detection, imaging and characterization of AuNPs in both biological and tumour samples. Spatially accurate imaging on the nanoscale poses a serious challenge requiring high- or super-resolution imaging techniques. In this mini review, we discuss the challenges in using AuNPs as radiosensitizers as well as various current and novel imaging techniques designed to validate the uptake, distribution and localization in mammalian cells. In our own work, we have used multiphoton excited plasmon resonance imaging to map the AuNP intracellular distribution. The benefits and limitations of this approach will also be discussed in some detail. In some cases, the same “excitation” mechanism as is used in an imaging modality can be harnessed to make it also a part of therapy modality (e.g. phototherapy)—such examples are discussed in passing as extensions to the imaging modality concerned.

Biological mechanisms of gold nanoparticle radiosensitization

“…Several approaches can be used to image the uptake and distribution of GNPs throughout the cell, including localized surface plasmon resonance, photoacoustic imaging, computerized tomography, X-ray fluorescence computed tomography and electron microscopy. Each technique will have individual advantages and limitations, so it can be worthwhile to apply multiple techniques in order to improve the reliability of diagnostics and treatments (Botchway et al 2015 ).…”

Gold Nanoparticle Mediated Phototherapy for Cancer

“…Although glioma cells and brain tumors are kept from the circulation by the blood-brain barrier, they can be targeted and effectively radiosensitized by PEGylated Journal of Nanomaterials gold nanoparticles, inducing DNA damage enhancement, cancer cell eradication, and survival improvement [147]. Now, radiotherapy with modified gold nanoparticles by targeting molecules such as glucose, folate, cisplatin, peptides, anti-EGFR, and thioglucose and combination with imaging and other therapy are the tendency [141,[157][158][159][160][161][162][163] Moreover, Polf et al found that killing of GNPs laden prostate cancer cells was enhanced by about 15%-20% by proton beam radiotherapy compared to that of cancer cells alone [164]. Khoshgard et al treated HeLa tumor cells with various common low energy levels of orthovoltage X-rays and megavoltage gamma-rays (Co-60) to study the cell killing efficacy in the presence of folate modified GNPs and nonfunctionalized GNPs.…”

Nuclear Uptake of Gold Nanoparticles Deduced Using Dual‐Angle X‐Ray Fluorescence Mapping

“…However, it has been suggested that within such studies there is no unambiguous imaging evidence for uptake into the cell nucleus . Fluorescence microscopy is highly useful as a fast, easy, and low‐cost method to image multiple organelles at once.…”