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. 2015 Aug 28:13:52.
doi: 10.1186/s12951-015-0113-5.

Photo-thermal effect enhances the efficiency of radiotherapy using Arg-Gly-Asp peptides-conjugated gold nanorods that target αvβ3 in melanoma cancer cells

Ping Li  1   2 , Yi-Wen Shi  3 , Bing-Xin Li  4 , Wen-Cai Xu  5 , Ze-Liang Shi  6 , Chuanqing Zhou  7 , Shen Fu  8   9
Affiliations

Photo-thermal effect enhances the efficiency of radiotherapy using Arg-Gly-Asp peptides-conjugated gold nanorods that target αvβ3 in melanoma cancer cells

Ping Li et al. J Nanobiotechnology. .

Abstract

Background: Thermotherapy has been known to be one of the most effective adjuvants to radiotherapy (RT) in cancer treatment, but it is not widely implemented clinically due to some limitations, such as, inadequate temperature concentrations to the tumor tissue, nonspecific and non-uniform distribution of heat. So we constructed arginine-glycine-aspartate peptides-conjugated gold nanorods (RGD-GNRs) that target the alpha(v) beta(3) Integrin (αvβ3) and investigate whether the photo-thermal effect of RGD-GNRs by near infrared radiation (NIR) could enhance the efficiency of RT in melanoma cancer cells.

Results: RGD-GNRs could be seen both on the surface of the cell membranes and cytoplasm of A375 cells with high expression of αvβ3. After exposed to 808 nm NIR, RGD-GNRs with various concentrations could be rapidly heated up. Compared to other treatments, flow cytometric analysis indicated that RT + NIR + RGD-GNRs increased apoptosis (p < 0.001) and decreased the proportion of cells in the more radioresistant S phase (p = 0.014). Treated with NIR + RGD-GNRs, the radiosensitivity was also significantly enhanced (DMFSF2: 1.41).

Conclusion: Results of the current study showed the feasibility of using RGD-GNRs for synergetic RT with photo-thermal therapy. And it would greatly benefit the therapeutic effects of refractory or recurrent malignant cancers.

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Figures

Fig. 1
Fig. 1
a The TEM images of GNRs dispersed in PBS. Scale bar 50 nm. b The TEM images ofGNRs dispersed in PBS. Scale bar 20 nm. c Measured UV–VIS absorbance spectrum of the synthesized GNRs, showing peak extinction at 805 and 532 nm, respectively.
Fig. 2
Fig. 2
Cellular uptake of RGD-GNRs. a, b Representative photos of flow cytometry assay of the expression level of αvβ3 in A375 and MCF-7 cells. c, d TEM analysis of A375 (c) and MCF-7 cells (d) with and without internalized RGD-GNRs.
Fig. 3
Fig. 3
Heating curve of different concentrations of GNRs (a) and RGD-GNRs (b) (0, 0.05, 0.1, 0.5, 1, 2 mg/ml) under 808 nm NIR at a power density of 1 W/cm2.
Fig. 4
Fig. 4
Radiosensitizing effect by RGD-GNRs and/or NIR. A375 cells were exposed with DMEM (control group), NIR, RGD-GNRs (50 μg/ml) or RGD-GNRs + NIR for 1 h, then irradiated at 0–8 Gy with 6MV-X ray. Cells were trypsinized, counted, and seeded at different dilutions. Colonies of 0.50 cells were counted approximately 2 weeks after treatment.
Fig. 5
Fig. 5
The apoptosis of the A375 cells after NIR or/and RGD-GNRs treatment. A375 cells were treated with RGD-GNRs or/and irradiation for 1 h prior to irradiation (6 mV X-rays with a dose of 4 Gy). The cells were stained with Annexin V and propidium iodide, and apoptosis was analyzed by flow cytometry after 24 h of treatment.
Fig. 6
Fig. 6
The changes in cell cycle distribution by treatment of RGD-GNRs and NIR in A375 cells. A375 cells were incubated with 0.05 mg/ml RGD-GNRs, then the cells were or were not irradiated with 808 nm NIR with the power density of 1 W/cm2 for 1 h. After 24 h, the cells were analyzed by flow cytometry.
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