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Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer.

Li K, Wen S, Larson AC, Shen M, Zhang Z, Chen Q, Shi X, Zhang G - Int J Nanomedicine (2013)

Bottom Line: The Gd-Au DENPs uptake, mainly in the cell cytoplasm, was confirmed by transmission electron microscopy.The cell cytotoxicity assay, cell morphology observation, and flow cytometry show that the developed Gd-Au DENPs have good biocompatibility in the given concentration range.Our results clearly suggest that the synthetic Gd-Au DENPs are amenable for dual-modality MR/CT imaging of breast cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.

ABSTRACT
Development of dual-mode or multi-mode imaging contrast agents is important for accurate and self-confirmatory diagnosis of cancer. We report a new multifunctional, dendrimer-based gold nanoparticle (AuNP) as a dual-modality contrast agent for magnetic resonance (MR)/computed tomography (CT) imaging of breast cancer cells in vitro and in vivo. In this study, amine-terminated generation 5 poly(amidoamine) dendrimers modified with gadolinium chelate (DOTA-NHS) and polyethylene glycol monomethyl ether were used as templates to synthesize AuNPs, followed by Gd(III) chelation and acetylation of the remaining dendrimer terminal amine groups; multifunctional dendrimer-entrapped AuNPs (Gd-Au DENPs) were formed. The formed Gd-Au DENPs were used for both in vitro and in vivo MR/CT imaging of human MCF-7 cancer cells. Both MR and CT images demonstrate that MCF-7 cells and the xenograft tumor model can be effectively imaged. The Gd-Au DENPs uptake, mainly in the cell cytoplasm, was confirmed by transmission electron microscopy. The cell cytotoxicity assay, cell morphology observation, and flow cytometry show that the developed Gd-Au DENPs have good biocompatibility in the given concentration range. Our results clearly suggest that the synthetic Gd-Au DENPs are amenable for dual-modality MR/CT imaging of breast cancer cells.

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TEM image and size distribution histogram of Gd-Au DENPs.Abbreviations: Gd-Au DENP, dendrimer-entrapped gold nanoparticle; TEM, transmission electron microscopy.
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f2-ijn-8-2589: TEM image and size distribution histogram of Gd-Au DENPs.Abbreviations: Gd-Au DENP, dendrimer-entrapped gold nanoparticle; TEM, transmission electron microscopy.

Mentions: Similar to our previous study,26 amine-terminated G5 PAMAM dendrimers were multifunctionalized through grafting gadolinium chelator DOTA-NHS and carboxylic acid functionalized methoxyl polyethylene glycol onto their surface. Using functional G5 dendrimers as templates, Au DENPs were prepared with sodium borohydride reduction chemistry. After chelating Gd(III) ions with the attached DOTA moieties onto the dendrimer surface, the remaining dendrimer terminal amine groups were acetylated to neutralize the positive charges. The obtained multifunctional Gd-Au DENPs were used for both MR and CT imaging of cancer cells in this study. Detailed characterization of the Gd-Au DENPs can be seen in our previous study26 and in the supporting information. Figure 1 shows the UV-Vis spectrum of the Gd-Au DENPs. The surface plasma resonance peak located at 520 nm clearly indicates the formation of AuNPs. In addition, the size and morphology of the Gd-Au DENPs were characterized with TEM (Figure 2). It can be seen that the Gd-Au DENPs have a spherical shape and a uniform size distribution. The diameter of the Gd-Au DENPs was estimated to be 4.3 nm. Similar to our previous study,26 with the coexistence of two radiodense imaging elements of Gd(III) ions and AuNPs within one NP system, the formed Gd-Au DENPs display both T1 relaxivity (for T1 MR imaging mode) and X-ray attenuation property (for CT imaging mode), which enables MR/CT dual-mode imaging applications.


Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer.

Li K, Wen S, Larson AC, Shen M, Zhang Z, Chen Q, Shi X, Zhang G - Int J Nanomedicine (2013)

TEM image and size distribution histogram of Gd-Au DENPs.Abbreviations: Gd-Au DENP, dendrimer-entrapped gold nanoparticle; TEM, transmission electron microscopy.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3722039&req=5

f2-ijn-8-2589: TEM image and size distribution histogram of Gd-Au DENPs.Abbreviations: Gd-Au DENP, dendrimer-entrapped gold nanoparticle; TEM, transmission electron microscopy.
Mentions: Similar to our previous study,26 amine-terminated G5 PAMAM dendrimers were multifunctionalized through grafting gadolinium chelator DOTA-NHS and carboxylic acid functionalized methoxyl polyethylene glycol onto their surface. Using functional G5 dendrimers as templates, Au DENPs were prepared with sodium borohydride reduction chemistry. After chelating Gd(III) ions with the attached DOTA moieties onto the dendrimer surface, the remaining dendrimer terminal amine groups were acetylated to neutralize the positive charges. The obtained multifunctional Gd-Au DENPs were used for both MR and CT imaging of cancer cells in this study. Detailed characterization of the Gd-Au DENPs can be seen in our previous study26 and in the supporting information. Figure 1 shows the UV-Vis spectrum of the Gd-Au DENPs. The surface plasma resonance peak located at 520 nm clearly indicates the formation of AuNPs. In addition, the size and morphology of the Gd-Au DENPs were characterized with TEM (Figure 2). It can be seen that the Gd-Au DENPs have a spherical shape and a uniform size distribution. The diameter of the Gd-Au DENPs was estimated to be 4.3 nm. Similar to our previous study,26 with the coexistence of two radiodense imaging elements of Gd(III) ions and AuNPs within one NP system, the formed Gd-Au DENPs display both T1 relaxivity (for T1 MR imaging mode) and X-ray attenuation property (for CT imaging mode), which enables MR/CT dual-mode imaging applications.

Bottom Line: The Gd-Au DENPs uptake, mainly in the cell cytoplasm, was confirmed by transmission electron microscopy.The cell cytotoxicity assay, cell morphology observation, and flow cytometry show that the developed Gd-Au DENPs have good biocompatibility in the given concentration range.Our results clearly suggest that the synthetic Gd-Au DENPs are amenable for dual-modality MR/CT imaging of breast cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.

ABSTRACT
Development of dual-mode or multi-mode imaging contrast agents is important for accurate and self-confirmatory diagnosis of cancer. We report a new multifunctional, dendrimer-based gold nanoparticle (AuNP) as a dual-modality contrast agent for magnetic resonance (MR)/computed tomography (CT) imaging of breast cancer cells in vitro and in vivo. In this study, amine-terminated generation 5 poly(amidoamine) dendrimers modified with gadolinium chelate (DOTA-NHS) and polyethylene glycol monomethyl ether were used as templates to synthesize AuNPs, followed by Gd(III) chelation and acetylation of the remaining dendrimer terminal amine groups; multifunctional dendrimer-entrapped AuNPs (Gd-Au DENPs) were formed. The formed Gd-Au DENPs were used for both in vitro and in vivo MR/CT imaging of human MCF-7 cancer cells. Both MR and CT images demonstrate that MCF-7 cells and the xenograft tumor model can be effectively imaged. The Gd-Au DENPs uptake, mainly in the cell cytoplasm, was confirmed by transmission electron microscopy. The cell cytotoxicity assay, cell morphology observation, and flow cytometry show that the developed Gd-Au DENPs have good biocompatibility in the given concentration range. Our results clearly suggest that the synthetic Gd-Au DENPs are amenable for dual-modality MR/CT imaging of breast cancer cells.

Show MeSH
Related in: MedlinePlus