Gold nanoparticles and their alternatives for radiation therapy enhancement

Abstract

Radiation therapy is one of the most commonly used treatments for cancer. The dose of delivered ionizing radiation can be amplified by the presence of high-Z materials via an enhancement of the photoelectric effect; the most widely studied material is gold (atomic number 79). However, a large amount is needed to obtain a significant dose enhancement, presenting a challenge for delivery. In order to make this technique of broader applicability, the gold must be targeted, or alternative formulations developed that do not rely solely on the photoelectric effect. One possible approach is to excite scintillating nanoparticles with ionizing radiation, and then exploit energy transfer between these particles and attached dyes in a manner analogous to photodynamic therapy (PDT). Doped rare-earth halides and semiconductor quantum dots have been investigated for this purpose. However, although the spectrum of emitted light after radiation excitation is usually similar to that seen with light excitation, the yield is not. Measurement of scintillation yields is challenging, and in many cases has been done only for bulk materials, with little understanding of how the principles translate to the nanoscale. Another alternative is to use local heating using gold or iron, followed by application of ionizing radiation. Hyperthermia pre-sensitizes the tumors, leading to an improved response. Another approach is to use chemotherapeutic drugs that can radiosensitize tumors. Drugs may be attached to high-Z nanoparticles or encapsulated. This article discusses each of these techniques, giving an overview of the current state of nanoparticle-assisted radiation therapy and future directions.

Radiosensitizing Effect of TRPV1 Channel Inhibitors in Cancer Cells

“…Recently, loading of gold nanoparticles into tumors has been introduced for radiosensitization, 27,28) but issues regarding photon energy and gold nanoparticle size remain. 16) Another approach is inhibition of Hsp, 17) which is abundantly overexpressed in many human tumor cells and blocks formation of apoptosome (ApaS-1/caspase-9/cytochrome c), leading to activation of caspase-3 and induction of apoptosis.…”

Optimal method of gold nanoparticle administration in melanoma‑bearing mice

“…The mechanism underlying the radiosensitizing effect of GNPs is not fully understood and a number of mechanisms have been suggested, including increased photoelectric photon absorption with a high-Z material, or an insult to the tumor blood vessels via an anti-angiogenic effect (3,7,8). In a previous study, GNPs were administered via intravenous (IV) injection or direct intratumoral (IT) injection (5); however, to the best of our knowledge, no studies have been performed to compare these two routes of administration.…”

“…Over the next decade, numerous studies were performed to investigate the optimal treatment parameters (2)(3)(4)(5)(6). The mechanism underlying the radiosensitizing effect of GNPs is not fully understood and a number of mechanisms have been suggested, including increased photoelectric photon absorption with a high-Z material, or an insult to the tumor blood vessels via an anti-angiogenic effect (3,7,8).…”

Layer-by-layer capsules as smart delivery systems of CeO2 nanoparticle-based theranostic agents

“…Multifunctional bismuth sulfide nanocapsules can be used in combined ultrasonic and radiation therapy [10]. The complex therapy uses magnetic iron oxide particles that also have low toxicity [11], and dextran-coated iron oxide nanoparticles decrease tumor growth in a breast cancer model by the combined action of hyperthermia and radiation [8]. Gadolinium oxide nanoparticles (Gd 2 O 3 ) are also considered an alternative to gold nanoparticles.…”

“…For example, heavy metal nanoparticles (mostly gold nanoparticles) are used in radiotheranostics (radiodiagnostics and radiotherapy) of tumors [5][6][7][8]. Bismuth oxide nanoparticles have also been shown to enhance the effect upon irradiation [9] and can replace gold nanoparticles.…”