Enhanced Radiosensitization of Gold Nanospikes via Hyperthermia in Combined Cancer Radiation and Photothermal Therapy.
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.
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University , Nanjing 210096, P. R. China.
Ningning
N
Ma
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University , Nanjing 210096, P. R. China.
Yao-Wen
YW
Jiang
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University , Nanjing 210096, P. R. China.
Xiaodong
X
Zhang
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University , Nanjing 210096, P. R. China.
Hao
H
Wu
Department of Chemistry, University of Michigan , 930 North University Avenue, Ann Arbor, Michigan 48109, United States.
John N
JN
Myers
Institute of Neurobiology, School of Medicine, Southeast University , Nanjing 210096, P. R. China.
Peidang
P
Liu
Institute of Neurobiology, School of Medicine, Southeast University , Nanjing 210096, P. R. China.
Haizhen
H
Jin
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University , Nanjing 210096, P. R. China.
Ning
N
Gu
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University , Nanjing 210096, P. R. China.
Nongyue
N
He
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University , Nanjing 210096, P. R. China.
Fu-Gen
FG
Wu
Department of Chemistry, University of Michigan , 930 North University Avenue, Ann Arbor, Michigan 48109, United States.
Zhan
Z
Chen
D045744:Cell Line, Tumor; D006046:Gold; D006801:Humans; D006979:Hyperthermia, Induced; D049329:Nanostructures; D009369:Neoplasms; D010789:Phototherapy
D006046:Gold
X-ray radiation therapy; gold nanospikes; photothermal therapy; radiosensitizing; synergistic effect