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Bioresponsive antisense DNA gold nanobeacons as a hybrid in vivo theranostics platform for the inhibition of cancer cells and metastasis.

Bao C, Conde J, Curtin J, Artzi N, Tian F, Cui D - Sci Rep (2015)

Bottom Line: Gold nanobeacons can be used as a powerful tool for cancer theranostics.The systemic administration of the anti-Kras nanobeacons resulted in approximately 60% tumor size reduction and a 90% reduction in tumor vascularization.More important, the inhibition of the Kras gene expression in gastric tumors prevents the occurrence of metastasis to lung (80% reduction), increasing mice survival in more than 85%.

View Article: PubMed Central - PubMed

Affiliation: Institute of Nano Biomedicine and Engineering, Key Lab. of Thin Film and Microfabrication Technology of Ministry of Education, Department of instrument science and engineering, School of Electronic Information and Electrical Engineering, National Center for Translational Medicine, Shanghai Jiao Tong University, P.R.China.

ABSTRACT
Gold nanobeacons can be used as a powerful tool for cancer theranostics. Here, we proposed a nanomaterial platform based on gold nanobeacons to detect, target and inhibit the expression of a mutant Kras gene in an in vivo murine gastric cancer model. The conjugation of fluorescently-labeled antisense DNA hairpin oligonucleotides to the surface of gold nanoparticles enables using their localized surface plasmon resonance properties to directly track the delivery to the primary gastric tumor and to lung metastatic sites. The fluorescently labeled nanobeacons reports on the interaction with the target as the fluorescent Cy3 signal is quenched by the gold nanoparticle and only emit light following conjugation to the Kras target owing to reorganization and opening of the nanobeacons, thus increasing the distance between the dye and the quencher. The systemic administration of the anti-Kras nanobeacons resulted in approximately 60% tumor size reduction and a 90% reduction in tumor vascularization. More important, the inhibition of the Kras gene expression in gastric tumors prevents the occurrence of metastasis to lung (80% reduction), increasing mice survival in more than 85%. Our developed platform can be easily adjusted to hybridize with any specific target and provide facile diagnosis and treatment for neoplastic diseases.

No MeSH data available.


Related in: MedlinePlus

(A) Histological analysis of gastric tumor and lung tissue indicating a reduced vascularization in the primary tumor and a decrease in tumoral clones in lung tissue treated with anti-Kras nanobeacons only. Nonsense nanobeacons group present inflammatory cells accumulation at bronchoalveolar junction and thickened local alveolar walls and high prevalence of tumoral clones (arrows). (B) Representative confocal microscopy images of lung tissue immunostaining, confirming the persistence of gastric cancer metastasis in the lungs. Blue: DAPI nuclear stain; red: Alexa-Fluor®594-labeled anti-human vimentin; green: FITC-labeled anti-human HLA. Scale bars, 20 μm. (C) anti-Kras nanobeacons treatment significantly reduced the number of spontaneous lung metastasis in gastric cancer model (***P < 0.005, n = 6 mice). (D) Kaplan-Meier survival curves for mice treated with nonsense (black) and anti-Kras (red) nanobeacons using Log-Rank test. Data points represent group mean ± SD (n = 6, ***P < 0.005).
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f5: (A) Histological analysis of gastric tumor and lung tissue indicating a reduced vascularization in the primary tumor and a decrease in tumoral clones in lung tissue treated with anti-Kras nanobeacons only. Nonsense nanobeacons group present inflammatory cells accumulation at bronchoalveolar junction and thickened local alveolar walls and high prevalence of tumoral clones (arrows). (B) Representative confocal microscopy images of lung tissue immunostaining, confirming the persistence of gastric cancer metastasis in the lungs. Blue: DAPI nuclear stain; red: Alexa-Fluor®594-labeled anti-human vimentin; green: FITC-labeled anti-human HLA. Scale bars, 20 μm. (C) anti-Kras nanobeacons treatment significantly reduced the number of spontaneous lung metastasis in gastric cancer model (***P < 0.005, n = 6 mice). (D) Kaplan-Meier survival curves for mice treated with nonsense (black) and anti-Kras (red) nanobeacons using Log-Rank test. Data points represent group mean ± SD (n = 6, ***P < 0.005).

Mentions: However, histological analysis in tumor tissue showed evidence of extensive reduced vascularization for anti-Kras nanobeacons loaded when compared to nonsense nanobeacons (Fig. 5A and Supplementary Figure S9), in accordance with tumor size reduction (see Fig. 2B). Moreover, H&E staining of lung tissue show that nonsense nanobeacon exposed groups exhibited inflammatory accumulation at the bronchoalveolar junction and thickened local alveolar walls (Fig. 5A and Supplementary Figure S9). Significant reduction in severe interstitial infiltration of inflammatory cells is noted in the anti-Kras nanobeacon treated group. Nonsense nanobeacon treated group showed a predominance of mononuclear cells, as well as perivascular and peribronchiolar edema, occurrence of hypercellularity and thickened local alveolar walls and septa and increased number of tumoral clones (arrows in Fig. 5A). These histological images confirmed an evident decrease (~90%) in the incidence and severity of tumor clones and metastasis in lung from mice treated with anti-Kras nanobeacons, after 5 days of exposure.


Bioresponsive antisense DNA gold nanobeacons as a hybrid in vivo theranostics platform for the inhibition of cancer cells and metastasis.

Bao C, Conde J, Curtin J, Artzi N, Tian F, Cui D - Sci Rep (2015)

(A) Histological analysis of gastric tumor and lung tissue indicating a reduced vascularization in the primary tumor and a decrease in tumoral clones in lung tissue treated with anti-Kras nanobeacons only. Nonsense nanobeacons group present inflammatory cells accumulation at bronchoalveolar junction and thickened local alveolar walls and high prevalence of tumoral clones (arrows). (B) Representative confocal microscopy images of lung tissue immunostaining, confirming the persistence of gastric cancer metastasis in the lungs. Blue: DAPI nuclear stain; red: Alexa-Fluor®594-labeled anti-human vimentin; green: FITC-labeled anti-human HLA. Scale bars, 20 μm. (C) anti-Kras nanobeacons treatment significantly reduced the number of spontaneous lung metastasis in gastric cancer model (***P < 0.005, n = 6 mice). (D) Kaplan-Meier survival curves for mice treated with nonsense (black) and anti-Kras (red) nanobeacons using Log-Rank test. Data points represent group mean ± SD (n = 6, ***P < 0.005).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4507177&req=5

f5: (A) Histological analysis of gastric tumor and lung tissue indicating a reduced vascularization in the primary tumor and a decrease in tumoral clones in lung tissue treated with anti-Kras nanobeacons only. Nonsense nanobeacons group present inflammatory cells accumulation at bronchoalveolar junction and thickened local alveolar walls and high prevalence of tumoral clones (arrows). (B) Representative confocal microscopy images of lung tissue immunostaining, confirming the persistence of gastric cancer metastasis in the lungs. Blue: DAPI nuclear stain; red: Alexa-Fluor®594-labeled anti-human vimentin; green: FITC-labeled anti-human HLA. Scale bars, 20 μm. (C) anti-Kras nanobeacons treatment significantly reduced the number of spontaneous lung metastasis in gastric cancer model (***P < 0.005, n = 6 mice). (D) Kaplan-Meier survival curves for mice treated with nonsense (black) and anti-Kras (red) nanobeacons using Log-Rank test. Data points represent group mean ± SD (n = 6, ***P < 0.005).
Mentions: However, histological analysis in tumor tissue showed evidence of extensive reduced vascularization for anti-Kras nanobeacons loaded when compared to nonsense nanobeacons (Fig. 5A and Supplementary Figure S9), in accordance with tumor size reduction (see Fig. 2B). Moreover, H&E staining of lung tissue show that nonsense nanobeacon exposed groups exhibited inflammatory accumulation at the bronchoalveolar junction and thickened local alveolar walls (Fig. 5A and Supplementary Figure S9). Significant reduction in severe interstitial infiltration of inflammatory cells is noted in the anti-Kras nanobeacon treated group. Nonsense nanobeacon treated group showed a predominance of mononuclear cells, as well as perivascular and peribronchiolar edema, occurrence of hypercellularity and thickened local alveolar walls and septa and increased number of tumoral clones (arrows in Fig. 5A). These histological images confirmed an evident decrease (~90%) in the incidence and severity of tumor clones and metastasis in lung from mice treated with anti-Kras nanobeacons, after 5 days of exposure.

Bottom Line: Gold nanobeacons can be used as a powerful tool for cancer theranostics.The systemic administration of the anti-Kras nanobeacons resulted in approximately 60% tumor size reduction and a 90% reduction in tumor vascularization.More important, the inhibition of the Kras gene expression in gastric tumors prevents the occurrence of metastasis to lung (80% reduction), increasing mice survival in more than 85%.

View Article: PubMed Central - PubMed

Affiliation: Institute of Nano Biomedicine and Engineering, Key Lab. of Thin Film and Microfabrication Technology of Ministry of Education, Department of instrument science and engineering, School of Electronic Information and Electrical Engineering, National Center for Translational Medicine, Shanghai Jiao Tong University, P.R.China.

ABSTRACT
Gold nanobeacons can be used as a powerful tool for cancer theranostics. Here, we proposed a nanomaterial platform based on gold nanobeacons to detect, target and inhibit the expression of a mutant Kras gene in an in vivo murine gastric cancer model. The conjugation of fluorescently-labeled antisense DNA hairpin oligonucleotides to the surface of gold nanoparticles enables using their localized surface plasmon resonance properties to directly track the delivery to the primary gastric tumor and to lung metastatic sites. The fluorescently labeled nanobeacons reports on the interaction with the target as the fluorescent Cy3 signal is quenched by the gold nanoparticle and only emit light following conjugation to the Kras target owing to reorganization and opening of the nanobeacons, thus increasing the distance between the dye and the quencher. The systemic administration of the anti-Kras nanobeacons resulted in approximately 60% tumor size reduction and a 90% reduction in tumor vascularization. More important, the inhibition of the Kras gene expression in gastric tumors prevents the occurrence of metastasis to lung (80% reduction), increasing mice survival in more than 85%. Our developed platform can be easily adjusted to hybridize with any specific target and provide facile diagnosis and treatment for neoplastic diseases.

No MeSH data available.


Related in: MedlinePlus