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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

Infrared microscopic imaging : deionized water (A) and GNS (B) in a tube upon NIR laser irradiation (790 nm, 0.3 W /cm2, 3 min); Subcutaneous tumor of GC without (C) and with (D) injection of GNS-PEG-CD44v6 upon NIR laser irradiation (790 nm, 1.5 W /cm2, 3 min). The nude mouse of GC subcutaneous xenograft, injected with nanoparticles before (E) and after (F) laser irradiation treatment (790 nm, 1.5 W /cm2, 3 min); (G) Tumor growth curves of four groups after treatment with GNS-PEG-CD44v6, GNS-PEG and PBS respectively upon NIR laser irradiation (790 nm, 0.8 W/cm2, 5 min); and the untreated control group. Error bars represent standard deviation (n = 10/group). *p < 0.05,**p < 0.01, (Student's t test); (H) Survival rate of GC tumor-bearing mice within eight weeks after treatment.
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Figure 6: Infrared microscopic imaging : deionized water (A) and GNS (B) in a tube upon NIR laser irradiation (790 nm, 0.3 W /cm2, 3 min); Subcutaneous tumor of GC without (C) and with (D) injection of GNS-PEG-CD44v6 upon NIR laser irradiation (790 nm, 1.5 W /cm2, 3 min). The nude mouse of GC subcutaneous xenograft, injected with nanoparticles before (E) and after (F) laser irradiation treatment (790 nm, 1.5 W /cm2, 3 min); (G) Tumor growth curves of four groups after treatment with GNS-PEG-CD44v6, GNS-PEG and PBS respectively upon NIR laser irradiation (790 nm, 0.8 W/cm2, 5 min); and the untreated control group. Error bars represent standard deviation (n = 10/group). *p < 0.05,**p < 0.01, (Student's t test); (H) Survival rate of GC tumor-bearing mice within eight weeks after treatment.

Mentions: The temperature variation of GNS-PEG-CD44v6 solutions exposed to laser irradiation (λ = 790 nm, 1.5 W/cm2 for 5 min; Supplementary Fig. S5) was first estimated to validate the photothermal therapy (PTT) potential of GNS-PEG-CD44v6 towards GCSCs. The temperature of the solution rose rapidly from 28°C to 61°C within 3 min, which was sufficient to induce cell damage (1.5 W/cm2) 38. The temperature could still rise to about 40 °C when the laser intensity was reduced to 0.3 W/cm2 (Fig.6A-B). The probe could generate heat upon laser irradiation due to an excellent plasmon absorption band in NIR. By contrast, after irradiating with equal laser intensities in PBS or water, very little temperature changes could be observed (minimal increase within 3°C). Compared with the NIR-induced heat conversion of gold nanostars, the temperature of the gold nanorods solution with the same Au content rose to about 33°C (Supplementary Fig. S5) upon the same power density of laser irradiation (1.5 W/cm2), which was much lower than the range of temperatures for GNS. The data described above demonstrated the excellent photothermal conversion efficiency of the anisotropic GNS over GNR and that GNS-PEG-CD44v6 could be an excellent nanoprobe for GCSC PTT.


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)

Infrared microscopic imaging : deionized water (A) and GNS (B) in a tube upon NIR laser irradiation (790 nm, 0.3 W /cm2, 3 min); Subcutaneous tumor of GC without (C) and with (D) injection of GNS-PEG-CD44v6 upon NIR laser irradiation (790 nm, 1.5 W /cm2, 3 min). The nude mouse of GC subcutaneous xenograft, injected with nanoparticles before (E) and after (F) laser irradiation treatment (790 nm, 1.5 W /cm2, 3 min); (G) Tumor growth curves of four groups after treatment with GNS-PEG-CD44v6, GNS-PEG and PBS respectively upon NIR laser irradiation (790 nm, 0.8 W/cm2, 5 min); and the untreated control group. Error bars represent standard deviation (n = 10/group). *p < 0.05,**p < 0.01, (Student's t test); (H) Survival rate of GC tumor-bearing mice within eight weeks after treatment.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4493535&req=5

Figure 6: Infrared microscopic imaging : deionized water (A) and GNS (B) in a tube upon NIR laser irradiation (790 nm, 0.3 W /cm2, 3 min); Subcutaneous tumor of GC without (C) and with (D) injection of GNS-PEG-CD44v6 upon NIR laser irradiation (790 nm, 1.5 W /cm2, 3 min). The nude mouse of GC subcutaneous xenograft, injected with nanoparticles before (E) and after (F) laser irradiation treatment (790 nm, 1.5 W /cm2, 3 min); (G) Tumor growth curves of four groups after treatment with GNS-PEG-CD44v6, GNS-PEG and PBS respectively upon NIR laser irradiation (790 nm, 0.8 W/cm2, 5 min); and the untreated control group. Error bars represent standard deviation (n = 10/group). *p < 0.05,**p < 0.01, (Student's t test); (H) Survival rate of GC tumor-bearing mice within eight weeks after treatment.
Mentions: The temperature variation of GNS-PEG-CD44v6 solutions exposed to laser irradiation (λ = 790 nm, 1.5 W/cm2 for 5 min; Supplementary Fig. S5) was first estimated to validate the photothermal therapy (PTT) potential of GNS-PEG-CD44v6 towards GCSCs. The temperature of the solution rose rapidly from 28°C to 61°C within 3 min, which was sufficient to induce cell damage (1.5 W/cm2) 38. The temperature could still rise to about 40 °C when the laser intensity was reduced to 0.3 W/cm2 (Fig.6A-B). The probe could generate heat upon laser irradiation due to an excellent plasmon absorption band in NIR. By contrast, after irradiating with equal laser intensities in PBS or water, very little temperature changes could be observed (minimal increase within 3°C). Compared with the NIR-induced heat conversion of gold nanostars, the temperature of the gold nanorods solution with the same Au content rose to about 33°C (Supplementary Fig. S5) upon the same power density of laser irradiation (1.5 W/cm2), which was much lower than the range of temperatures for GNS. The data described above demonstrated the excellent photothermal conversion efficiency of the anisotropic GNS over GNR and that GNS-PEG-CD44v6 could be an excellent nanoprobe for GCSC PTT.

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