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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

Fluorescence-activated cell sorter (FACS) analysis of candidate surface markers for GCSCs. Horizontal axis: FITC-CD44 (A) / FITC-CD44v6 (B); Vertical axis: count; inverted microscope images of CD44+sphere cells in different generations (C and D, 1st generation and 3rd generation) and CD44-sphere cells (E) in the 3rd generation; (F) spheroid colony formation assay between CD44+ cells and CD44- cells in four generations.
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Figure 3: Fluorescence-activated cell sorter (FACS) analysis of candidate surface markers for GCSCs. Horizontal axis: FITC-CD44 (A) / FITC-CD44v6 (B); Vertical axis: count; inverted microscope images of CD44+sphere cells in different generations (C and D, 1st generation and 3rd generation) and CD44-sphere cells (E) in the 3rd generation; (F) spheroid colony formation assay between CD44+ cells and CD44- cells in four generations.

Mentions: CD44 has been identified as a potential marker of GCSCs. The CD44+ GC cells sorted from MKN-45 showed stem-cell properties, including self-renewal ability and tumorigenicity 11. MKN-45 showed high level expression of CD44, up to 98%. The expression rate of human CD44v6 was 97%, which was slightly lower than the expression ratio of CD44 molecule (Fig.3A-B). CD44 family contains standard form (CD44s) and isoforms (CD44v). Interestingly, CD44 isoforms, especially CD44v6, were found to comprise the major portion in CD44 family in GCs according to previous reports 26, 27 and our analysis results from flow cytometry. The sorted CD44+ cells can produce spheroid colonies with a diameter of 50~100 μm in serum-free media under non-adherent conditions, while most CD44- cells can't (Fig.3C-F). These CD44+ cells can be cultivated in vitro for more than four weeks, which is considered as the indication of self-renewal ability. Different from Jungmin Park's work in which the CD44-targetable and near-infrared-sensitive supramolecular hydrogels (NIRSHs) were fabricated for fluorescence molecular imaging of stem-like GC cells 36, CD44-expressing spheroid colonies (i.e., GCSCs) were chosen as target cells for evaluation of targeting imaging and photothermal ability of GNS-PEG-CD44v6 in our study.


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)

Fluorescence-activated cell sorter (FACS) analysis of candidate surface markers for GCSCs. Horizontal axis: FITC-CD44 (A) / FITC-CD44v6 (B); Vertical axis: count; inverted microscope images of CD44+sphere cells in different generations (C and D, 1st generation and 3rd generation) and CD44-sphere cells (E) in the 3rd generation; (F) spheroid colony formation assay between CD44+ cells and CD44- cells in four generations.
© Copyright Policy
Related In: Results  -  Collection

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Figure 3: Fluorescence-activated cell sorter (FACS) analysis of candidate surface markers for GCSCs. Horizontal axis: FITC-CD44 (A) / FITC-CD44v6 (B); Vertical axis: count; inverted microscope images of CD44+sphere cells in different generations (C and D, 1st generation and 3rd generation) and CD44-sphere cells (E) in the 3rd generation; (F) spheroid colony formation assay between CD44+ cells and CD44- cells in four generations.
Mentions: CD44 has been identified as a potential marker of GCSCs. The CD44+ GC cells sorted from MKN-45 showed stem-cell properties, including self-renewal ability and tumorigenicity 11. MKN-45 showed high level expression of CD44, up to 98%. The expression rate of human CD44v6 was 97%, which was slightly lower than the expression ratio of CD44 molecule (Fig.3A-B). CD44 family contains standard form (CD44s) and isoforms (CD44v). Interestingly, CD44 isoforms, especially CD44v6, were found to comprise the major portion in CD44 family in GCs according to previous reports 26, 27 and our analysis results from flow cytometry. The sorted CD44+ cells can produce spheroid colonies with a diameter of 50~100 μm in serum-free media under non-adherent conditions, while most CD44- cells can't (Fig.3C-F). These CD44+ cells can be cultivated in vitro for more than four weeks, which is considered as the indication of self-renewal ability. Different from Jungmin Park's work in which the CD44-targetable and near-infrared-sensitive supramolecular hydrogels (NIRSHs) were fabricated for fluorescence molecular imaging of stem-like GC cells 36, CD44-expressing spheroid colonies (i.e., GCSCs) were chosen as target cells for evaluation of targeting imaging and photothermal ability of GNS-PEG-CD44v6 in our study.

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