Thiol-PEG-carboxyl-stabilized Fe₂O ₃/Au nanoparticles targeted to CD105: synthesis, characterization and application in MR imaging of tumor angiogenesis.
OBJECTIVE
To detect tumor angiogenesis in tumor-bearing mice using thiol-PEG-carboxyl-stabilized Fe2O3/Au nanoparticles targeted to CD105 on magnetic resonance imaging (MRI).


METHODS
Fe2O3/Au nanoparticles (hybrids) were prepared by reducing Au(3+) on the surface of Fe2O3 nanoparticles. Hybrids were stabilized with thiol-PEG-carboxyl via the Au-S covalent bond, and further conjugated with anti-CD105 antibodies through amide linkages. Characteristics of the hybrid-PEG-CD105 nanoparticles were evaluated. Using these nanoparticles, the labeling specificity of human umbilical vein endothelial cells (HUVECs) was evaluated in vitro. MRI T2-weighted images were obtained at different time points after intravenous administration of the hybrid-PEG-CD105 nanoparticles in the tumor-bearing mice. After MR imaging, the breast cancer xenografts were immediately resected for immunohistochemistry staining and Prussian blue staining to measure the tumor microvessel density (MVD) and evaluate the labeling of blood microvessels by the hybrid-PEG-CD105 nanoparticles in vivo.


RESULTS
The mean diameter of the hybrid-PEG-CD105 nanoparticles was 56.6 ± 8.0 nm, as measured by transmission electron microscopy (TEM). Immune activity of the hybrid-PEG-CD105 nanoparticles was 53% of that of the anti-CD105 antibody, as detected by enzyme-linked immunosorbent assay (ELISA). The specific binding of HUVECs with the hybrid-PEG-CD105 nanoparticles was proved by immunostaining and Prussian blue staining in vitro. For breast cancer xenografts, the combination of the hybrid-PEG-CD105 nanoparticles with blood microvessels was detectable by MRI after 60 min administration of the contrast agent. The T2* relative signal intensity (SIR) was positively correlated with the tumor MVD (R(2)=0.8972).


CONCLUSIONS
Anti-CD105 antibody-coupled, thiol-PEG-carboxyl-stabilized core-shell Fe2O3/Au nanoparticles can efficiently target CD105 expressed by HUVECs. Furthermore, the hybrid-PEG-CD105 nanoparticles can be used to detect tumor angiogenesis in vivo.
Department of Radiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Song
S
Zhang
Department of Radiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Mingfu
M
Gong
Department of Radiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Dong
D
Zhang
Department of Radiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Hua
H
Yang
Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China.
Fabao
F
Gao
Department of Radiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: zlgxqyy@163.com.
Liguang
L
Zou
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000138:chemical synthesis; D015195:Drug Design; D004355:Drug Stability; D000071063:Endoglin; D005079:Excipients / Q000737:chemistry; D006046:Gold / Q000737:chemistry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology; D058185:Magnetite Nanoparticles / Q000737:chemistry; D051379:Mice; D058726:Nanoconjugates / Q000737:chemistry* / Q000648:ultrastructure; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000473:pathology*; D011092:Polyethylene Glycols / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013438:Sulfhydryl Compounds / Q000737:chemistry
D000911:Antibodies, Monoclonal; D003287:Contrast Media; D000071063:Endoglin; C502004:Eng protein, mouse; D005079:Excipients; D047908:Intracellular Signaling Peptides and Proteins; D058185:Magnetite Nanoparticles; D058726:Nanoconjugates; D013438:Sulfhydryl Compounds; D011092:Polyethylene Glycols; D006046:Gold
Angiogenesis; Colloid gold; Endoglin protein; Magnetic resonance imaging; Molecular imaging; Superparamagnetic iron oxide