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CD44v6 Monoclonal Antibody-Conjugated Gold Nanostars for Targeted Photoacoustic Imaging and Plasmonic Photothermal Therapy of Gastric Cancer Stem-like Cells.

Liang S, Li C, Zhang C, Chen Y, Xu L, Bao C, Wang X, Liu G, Zhang F, Cui D - Theranostics (2015)

Bottom Line: Developing safe and effective nanoprobes for targeted imaging and selective therapy of gastric cancer stem cells (GCSCs) has become one of the most promising anticancer strategies.It was observed that the prepared nanoprobes had high affinity towards GCSC spheroid colonies and destroyed them completely with a low power density upon near-infrared (NIR) laser treatment (790 nm, 1.5 W/cm(2), 5 min) in vitro experiment.Subsequently, biodistribution and photothermal therapeutic effects after being intravenously injected with the prepared nanoprobes were assessed.

View Article: PubMed Central - PubMed

Affiliation: 1. Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P. R. China ; 2. Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Department of Instrument Science and Engineering, Research Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.

ABSTRACT
Developing safe and effective nanoprobes for targeted imaging and selective therapy of gastric cancer stem cells (GCSCs) has become one of the most promising anticancer strategies. Herein, gold nanostars-based PEGylated multifunctional nanoprobes were prepared with conjugated CD44v6 monoclonal antibodies (CD44v6-GNS) as the targeting ligands. It was observed that the prepared nanoprobes had high affinity towards GCSC spheroid colonies and destroyed them completely with a low power density upon near-infrared (NIR) laser treatment (790 nm, 1.5 W/cm(2), 5 min) in vitro experiment. Orthotopic and subcutaneous xenografted nude mice models of human gastric cancer were established. Subsequently, biodistribution and photothermal therapeutic effects after being intravenously injected with the prepared nanoprobes were assessed. Photoacoustic imaging revealed that CD44v6-GNS nanoprobes could target the gastric cancer vascular system actively at 4 h post-injection, while the probes inhibited tumor growth remarkably upon NIR laser irradiation, and even extended survivability of the gastric cancer-bearing mice. The CD44v6-GNS nanoprobes exhibited great potential for applications of gastric cancer targeted imaging and photothermal therapy in the near future.

No MeSH data available.


Related in: MedlinePlus

(A) GNS-PEG-CD44v6 in vitro in the concentration range of 0.0625 mg/mL to 1 mg/mL; Dependence of PA signals on the nanoparticle concentration (B) and wavelengths (C); The error bars indicate the standard deviation for each measurement (n = 3); (D) PA imaging in vivo in the UCLA mold: Representative PA sequential images acquired before injection (0 h) and after injection (2, 4, and 24 h) of the GNS-PEG-CD44 (the first panel - sub tumor, the second panel - orthotopic tumor), GNS-PEG-CD44v6 (the third panel - sub tumor, the fourth panel - orthotopic tumor) and GNS-PEG (the fifth panel - control).
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Figure 7: (A) GNS-PEG-CD44v6 in vitro in the concentration range of 0.0625 mg/mL to 1 mg/mL; Dependence of PA signals on the nanoparticle concentration (B) and wavelengths (C); The error bars indicate the standard deviation for each measurement (n = 3); (D) PA imaging in vivo in the UCLA mold: Representative PA sequential images acquired before injection (0 h) and after injection (2, 4, and 24 h) of the GNS-PEG-CD44 (the first panel - sub tumor, the second panel - orthotopic tumor), GNS-PEG-CD44v6 (the third panel - sub tumor, the fourth panel - orthotopic tumor) and GNS-PEG (the fifth panel - control).

Mentions: PA imaging can be used in a hybrid modality fashion to extend the anatomic and hemodynamic sensitivities of clinical ultrasound. The GNS, an emerging contrast agent, has been selected and applied to photoacoustic tomography noninvasively with its distribution monitored simultaneously 51, 52. Additionally, the therapeutic response could be quantified by calculating the intensities of PA signals in a timely manner 53. GNS-PEG-CD44v6 (Fig. 7A) was first synthesized and applied to detect GCSC in PA imaging in both orthotopic and subcutaneous GC xenografted models in vivo. The mice injected with GNS-PEG and GNS-PEG-CD44 were set as controls. The accumulation and distribution of the probe in the tumor were whole-process monitored. Plasmon-resonant nanostars are excellent contrast agents for in vivo photoacoustic tomography, with a detection limit at 1 ppm (~1 μg/mL) 32. There is a nice linear relationship (R2 = 0.996) between the PA signal amplitude and the concentration (Fig. 7B) in vitro. However, it is not between the PA signal amplitude and the excitation wavelength (Fig. 7C). The PA amplitudes reach a maximum at the 950 nm wavelength, which is not the SPR peak wavelength of the gold nanostars. The PA amplitudes are not consistent with the absorbance curve of the GNS, which is different from the gold nanorods 54. The discrepancy could be explained by the differences in heat transfer from the particle to the medium and the scattering of light 55, 56.


CD44v6 Monoclonal Antibody-Conjugated Gold Nanostars for Targeted Photoacoustic Imaging and Plasmonic Photothermal Therapy of Gastric Cancer Stem-like Cells.

Liang S, Li C, Zhang C, Chen Y, Xu L, Bao C, Wang X, Liu G, Zhang F, Cui D - Theranostics (2015)

(A) GNS-PEG-CD44v6 in vitro in the concentration range of 0.0625 mg/mL to 1 mg/mL; Dependence of PA signals on the nanoparticle concentration (B) and wavelengths (C); The error bars indicate the standard deviation for each measurement (n = 3); (D) PA imaging in vivo in the UCLA mold: Representative PA sequential images acquired before injection (0 h) and after injection (2, 4, and 24 h) of the GNS-PEG-CD44 (the first panel - sub tumor, the second panel - orthotopic tumor), GNS-PEG-CD44v6 (the third panel - sub tumor, the fourth panel - orthotopic tumor) and GNS-PEG (the fifth panel - control).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4493535&req=5

Figure 7: (A) GNS-PEG-CD44v6 in vitro in the concentration range of 0.0625 mg/mL to 1 mg/mL; Dependence of PA signals on the nanoparticle concentration (B) and wavelengths (C); The error bars indicate the standard deviation for each measurement (n = 3); (D) PA imaging in vivo in the UCLA mold: Representative PA sequential images acquired before injection (0 h) and after injection (2, 4, and 24 h) of the GNS-PEG-CD44 (the first panel - sub tumor, the second panel - orthotopic tumor), GNS-PEG-CD44v6 (the third panel - sub tumor, the fourth panel - orthotopic tumor) and GNS-PEG (the fifth panel - control).
Mentions: PA imaging can be used in a hybrid modality fashion to extend the anatomic and hemodynamic sensitivities of clinical ultrasound. The GNS, an emerging contrast agent, has been selected and applied to photoacoustic tomography noninvasively with its distribution monitored simultaneously 51, 52. Additionally, the therapeutic response could be quantified by calculating the intensities of PA signals in a timely manner 53. GNS-PEG-CD44v6 (Fig. 7A) was first synthesized and applied to detect GCSC in PA imaging in both orthotopic and subcutaneous GC xenografted models in vivo. The mice injected with GNS-PEG and GNS-PEG-CD44 were set as controls. The accumulation and distribution of the probe in the tumor were whole-process monitored. Plasmon-resonant nanostars are excellent contrast agents for in vivo photoacoustic tomography, with a detection limit at 1 ppm (~1 μg/mL) 32. There is a nice linear relationship (R2 = 0.996) between the PA signal amplitude and the concentration (Fig. 7B) in vitro. However, it is not between the PA signal amplitude and the excitation wavelength (Fig. 7C). The PA amplitudes reach a maximum at the 950 nm wavelength, which is not the SPR peak wavelength of the gold nanostars. The PA amplitudes are not consistent with the absorbance curve of the GNS, which is different from the gold nanorods 54. The discrepancy could be explained by the differences in heat transfer from the particle to the medium and the scattering of light 55, 56.

Bottom Line: Developing safe and effective nanoprobes for targeted imaging and selective therapy of gastric cancer stem cells (GCSCs) has become one of the most promising anticancer strategies.It was observed that the prepared nanoprobes had high affinity towards GCSC spheroid colonies and destroyed them completely with a low power density upon near-infrared (NIR) laser treatment (790 nm, 1.5 W/cm(2), 5 min) in vitro experiment.Subsequently, biodistribution and photothermal therapeutic effects after being intravenously injected with the prepared nanoprobes were assessed.

View Article: PubMed Central - PubMed

Affiliation: 1. Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P. R. China ; 2. Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Department of Instrument Science and Engineering, Research Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.

ABSTRACT
Developing safe and effective nanoprobes for targeted imaging and selective therapy of gastric cancer stem cells (GCSCs) has become one of the most promising anticancer strategies. Herein, gold nanostars-based PEGylated multifunctional nanoprobes were prepared with conjugated CD44v6 monoclonal antibodies (CD44v6-GNS) as the targeting ligands. It was observed that the prepared nanoprobes had high affinity towards GCSC spheroid colonies and destroyed them completely with a low power density upon near-infrared (NIR) laser treatment (790 nm, 1.5 W/cm(2), 5 min) in vitro experiment. Orthotopic and subcutaneous xenografted nude mice models of human gastric cancer were established. Subsequently, biodistribution and photothermal therapeutic effects after being intravenously injected with the prepared nanoprobes were assessed. Photoacoustic imaging revealed that CD44v6-GNS nanoprobes could target the gastric cancer vascular system actively at 4 h post-injection, while the probes inhibited tumor growth remarkably upon NIR laser irradiation, and even extended survivability of the gastric cancer-bearing mice. The CD44v6-GNS nanoprobes exhibited great potential for applications of gastric cancer targeted imaging and photothermal therapy in the near future.

No MeSH data available.


Related in: MedlinePlus