Enhanced Radiosensitization of Gold Nanospikes via Hyperthermia in Combined Cancer Radiation and Photothermal Therapy

Abstract

Metallic nanostructures as excellent candidates for nanosensitizers have shown enormous potentials in cancer radiotherapy and photothermal therapy. Clinically, a relatively low and safe radiation dose is highly desired to avoid damage to normal tissues. Therefore, the synergistic effect of the low-dosed X-ray radiation and other therapeutic approaches (or so-called "combined therapeutic strategy") is needed. Herein, we have synthesized hollow and spike-like gold nanostructures by a facile galvanic replacement reaction. Such gold nanospikes (GNSs) with low cytotoxicity exhibited high photothermal conversion efficiency (η = 50.3%) and had excellent photostability under cyclic near-infrared (NIR) laser irradiations. We have demonstrated that these GNSs can be successfully used for in vitro and in vivo X-ray radiation therapy and NIR photothermal therapy. For the in vitro study, colony formation assay clearly demonstrated that GNS-mediated photothermal therapy and X-ray radiotherapy reduced the cell survival fraction to 89% and 51%, respectively. In contrast, the cell survival fraction of the combined radio- and photothermal treatment decreased to 33%. The synergistic cancer treatment performance was attributable to the effect of hyperthermia, which efficiently enhanced the radiosensitizing effect of hypoxic cancer cells that were resistant to ionizing radiation. The sensitization enhancement ratio (SER) of GNSs alone was calculated to be about 1.38, which increased to 1.63 when the GNS treatment was combined with the NIR irradiation, confirming that GNSs are effective radiation sensitizers to enhance X-ray radiation effect through hyperpyrexia. In vivo tumor growth study indicated that the tumor growth inhibition (TGI) in the synergistically treated group reached 92.2%, which was much higher than that of the group treated with the GNS-enhanced X-ray radiation (TGI = 29.8%) or the group treated with the GNS-mediated photothermal therapy (TGI = 70.5%). This research provides a new method to employ GNSs as multifunctional nanosensitizers for synergistic NIR photothermal and X-ray radiation therapy in vitro and in vivo.

Emerging Strategies of Nanomaterial‐Mediated Tumor Radiosensitization

“…Therefore, when combing PTT with RT, the heat generated from PTT can elevate the oxygen level in cancer cells to make the cells more sensitive to radiation, and thus the RT therapeutic effect is availably strengthened. Up to date, a large number of literatures about PTT and RT synergetic therapy can be searched . And we roughly summarized the evolution trends of this synergetic strategy as follows.…”

“…Recently, the nanomaterials that play both roles of photothermal agents and radiosensitizers are widely researched due to their multifunctional properties and simply synthetic methods, such as Au, WS 2 Bi 2 S 3 , Bi 2 Se 3 , ReS 2 , Cu 3 BiS 3 , and WO 3− x nanoparticles. The NIR absorption ability of these nanoparticles allows them to act as photothermal agents for producing significant heat to eliminate tumor, and the high Z atom endows these nanoparticles with the ability to serve as radiosensitizers for accumulating more X‐ray energy in cells.…”

Nanocarrier‐Mediated Photochemotherapy and Photoradiotherapy

“…Nanomaterials used for this combination present high NIR absorbance and can produce a very localized increase in temperature while having a radiosensitizing effect. They are composed of inorganic materials commonly based on copper sulfides, quantum dots, or gold or bismuth containing compounds. In the following section, the application of these materials has been divided into PTT combined with either external radiotherapy or (internal) radionuclide therapy.…”

“…NIR irradiation has been combined with X‐ray therapy using a 125 kV X‐ray given in a single 10 Gy dose, resulting in a more than twofold increase of the tumor doubling time when compared with the single therapies. Gold nanospikes have been developed by Ma et al having a 50 nm diameter and excellent stability in PBS (phosphate buffered saline) . In vitro tests have revealed that cell survival is greatly reduced when phototherapy is combined with 6 MV X‐rays, and have led to in vivo studies in which the benefit of the combinational treatment has been evident resulting in pronounced tumor reduction in comparison to the individual treatments.…”

<p>Albumin exfoliated titanium disulfide nanosheet: a multifunctional nanoplatform for synergistic photothermal/radiation colon cancer therapy</p>

“…To overcome these drawbacks, a series of radio-sensitizers such as the two-dimensional (2D) layered transition metal dichalcogenides (TMDs) (MoS 2 , WS 2 , MoSe 2 , and ReS 2 ) and other inorganic materials have been prepared. [8][9][10][11][12][13] Most TMDs were reported to contain high-Z elements that can act as radio-sensitizers to promote the cancer RT effect by absorbing X-rays and concentrating the radiation dose within tumors. [14][15][16] For example, Shen and co-authors have prepared uniform ultrathin rhenium disulfide nanosheets for photothermal RT.…”