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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

Microscopy images of GCSC spheroid colonies treated with GNS-PEG and GNS-PEG-CD44v6 for 24 h after NIR laser irradiation (790 nm, 1.5W /cm 2, 5 min). All scale bars are 100 µm.
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Figure 5: Microscopy images of GCSC spheroid colonies treated with GNS-PEG and GNS-PEG-CD44v6 for 24 h after NIR laser irradiation (790 nm, 1.5W /cm 2, 5 min). All scale bars are 100 µm.

Mentions: To demonstrate the feasibility of selectively eradicating CD44+GCSCs by GNS-PEG-CD44v6, CD44+ spheroid colonies were incubated with specific CD44-targetable GNS-PEG-CD44v6 (test group) and GNS-PEG (control group) respectively at 37 °C for 24 h. Cells were rinsed with PBS (pH 7.4) to remove the unbound probe. After 5 min of the laser treatment (1.5W/cm2), a large portion of the GCSC spheroid colonies were damaged completely (empty area), as shown in Fig. 5. At 0.3 W/cm2, the colonies became dissociated, scattered and lost the original spheroidal structure (not shown in the article), whereas no obvious change could be observed in the control group because the free floating GNS-PEG that lacked labeling with CD44v6-antibodies could not be concentrated in spheroid colonies and removed by subsequent washing. To further determine the optimized laser intensity for PTT in vitro, cell viability assay was performed for the cells treated with GNS-PEG-CD44v6, which were exposed to NIR laser irradiation with different power densities (0.3, 0.6, 0.9, 1.2, 1.5 W/cm2). The cell viabilities were 94.2%, 78.5%, 39.3%, 10.8%, and 0.7%, respectively. It is manifested that it could still show toxicity and photothermal ablation effect to the GCSCs with the relatively low power density (Supplementary Fig. S6).


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)

Microscopy images of GCSC spheroid colonies treated with GNS-PEG and GNS-PEG-CD44v6 for 24 h after NIR laser irradiation (790 nm, 1.5W /cm 2, 5 min). All scale bars are 100 µm.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Microscopy images of GCSC spheroid colonies treated with GNS-PEG and GNS-PEG-CD44v6 for 24 h after NIR laser irradiation (790 nm, 1.5W /cm 2, 5 min). All scale bars are 100 µm.
Mentions: To demonstrate the feasibility of selectively eradicating CD44+GCSCs by GNS-PEG-CD44v6, CD44+ spheroid colonies were incubated with specific CD44-targetable GNS-PEG-CD44v6 (test group) and GNS-PEG (control group) respectively at 37 °C for 24 h. Cells were rinsed with PBS (pH 7.4) to remove the unbound probe. After 5 min of the laser treatment (1.5W/cm2), a large portion of the GCSC spheroid colonies were damaged completely (empty area), as shown in Fig. 5. At 0.3 W/cm2, the colonies became dissociated, scattered and lost the original spheroidal structure (not shown in the article), whereas no obvious change could be observed in the control group because the free floating GNS-PEG that lacked labeling with CD44v6-antibodies could not be concentrated in spheroid colonies and removed by subsequent washing. To further determine the optimized laser intensity for PTT in vitro, cell viability assay was performed for the cells treated with GNS-PEG-CD44v6, which were exposed to NIR laser irradiation with different power densities (0.3, 0.6, 0.9, 1.2, 1.5 W/cm2). The cell viabilities were 94.2%, 78.5%, 39.3%, 10.8%, and 0.7%, respectively. It is manifested that it could still show toxicity and photothermal ablation effect to the GCSCs with the relatively low power density (Supplementary Fig. S6).

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