PEGylated dendrimer-entrapped gold nanoparticles for in vivo blood pool and tumor imaging by computed tomography

Peng, Chen; Zheng, Linfeng; Chen, Qian; Shen, Mingwu; Guo, Rui; Wang, Han; Cao, Xueyan; Zhang, Guixiang; Shi, Xiangyang

doi:10.1016/j.biomaterials.2011.10.052

Cited by 367 publications

(363 citation statements)

References 34 publications

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“…23,27 The morphology of the cells after treatment with the Gd-Au DENPs was observed with optical microscopy (Nikon, Tokyo, Japan) after staining with hematoxylin and eosin (HE). The viability of cells treated with the Gd-Au DENPs was evaluated using an MTT assay.…”

Section: Cytotoxicity Of Gd-au Denpsmentioning

confidence: 99%

“…20,21 Additionally, the interior features of the dendrimers enable them to be used as templates or stabilizers for preparation of inorganic NPs, 22 such as gold and silver. Our previous studies 3,[23][24][25] have shown that the generation 5 (G5) PAMAM dendrimer-entrapped gold nanoparticles (Au DENPs) can be used as blood pool CT contrast agents or targeted cancer-specific CT agents. In a very recent study, 26 we have shown that Gd-loaded Au DENPs (Gd-Au DENPs) prepared using the facile dendrimer chemistry enable MR/CT dual-mode imaging of the heart, liver, kidney, and bladder of rat or mouse within a time frame of 45 minutes.…”

Section: Introductionmentioning

confidence: 99%

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

Li¹,

Wen²,

Larson³

et al. 2013

IJN

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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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Section: Cytotoxicity Of Gd-au Denpsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Li¹,

Wen²,

Larson³

et al. 2013

IJN

Self Cite

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“…[1][2][3] In addition, GNPs are promising as contrast media in several computed tomography (CT) imaging approaches due to the high attenuation coefficient of gold providing a greater contrast than commonly used iodine contrast agents. [4][5][6] Gold has mainly been considered for tumor imaging 7,8 frequently by taking advantage of the progressive permeation through transendothelial pores on tumor blood vessels (the enhanced permeability and retention effect) after intravenous (iv) application. 9 Some studies also achieved good CT imaging contrast after intratumoral injection of GNPs in xenograft tumor mouse models.…”

Section: Introductionmentioning

confidence: 99%

Gold nanoparticles allow detection of early-stage edema in mice via computed tomography imaging

Domey¹,

Teichgräber²,

Hilger³

2015

IJN

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Due to their high X-ray attenuation, gold nanoparticles (GNPs) emerged as preclinical contrast agents by giving high vasculature contrast. For this reason, GNPs are regularly applied for computed tomography (CT) imaging of tumors but not for the visualization of inflammation. The aim of this study was to evaluate the biocompatibility and applicability of preclinical GNPs (AuroVist™) of two different sizes (1.9 nm and 15 nm) for the detection of inflammation-associated phagocytes in early-stage edema. Both GNP variants were stable under in vitro conditions and achieved high micro-CT (mCT) contrast after embedment into agarose. Fifteen-nanometer GNPs were detected after uptake into macrophages via mCT imaging exhibiting higher X-ray contrast than cells treated with 1.9 nm GNPs and untreated ones. Both 1.9 nm and 15 nm GNPs exhibited good biocompatibility on murine macrophages according to ATP and cellular dehydrogenase levels. Reactive oxygen species levels produced by phagocytic cells decreased significantly ( P ≤0.05) after co-incubation with GNPs regardless of the size of the nanoparticle (NP) in comparison to untreated control cells. In vivo mCT studies of inflammation imaging revealed that GNPs with a diameter of 15 nm accumulated within subcutaneous edema 2 hours after injection with a maximum signaling 8 hours postinjection and could be detected up to 48 hours within the edema region. In contrast, 1.9 nm GNPs were not shown to accumulate at the site of the inflammation region and were mostly excreted via the renal system 2–4 hours after injection. In conclusion, our study demonstrated that both GNP variants (1.9 nm and 15 nm) were stable and biocompatible under in vitro conditions. However, only 15 nm NPs have the potential as contrast agent for phagocyte labeling and applications in CT imaging of inflammation on a cellular level.

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“…In the early days, dendrimers were only used as vectors of some imaging elements; for example, Mn(II) or Gd(III) chelating dendrimers were prepared as contrast agents for MRI applications; 88,91,94 dye-conjugated dendrimers were used for fluorescence imaging; 95,96 and dendrimer-entrapped Au nanoparticles (Au DENPs) or iodinated-compounds conjugated dendrimers were applied to CT. [97][98][99][100] With multi-signal elements and targeting molecules in one dendrimer molecule, dendrimers can easily target to the intended imagining organs. Dendrimers conjugated with folic acid (FA) and Cu 2+ were studied as bioprobes to target and image human cancers using synchrotron X-ray fluorescence analysis, and the results showed that the targeting probes increased the intensity of fluorescence signal compared to 93 Likewise, folate receptor-targeted dendrimer nanoclusters (DNCs) labeled with Gd can be used for MRI of cancers with high expression of folate-receptor.…”

Section: Dendrimers As Imaging Agentsmentioning

confidence: 99%

A review of molecular imaging of atherosclerosis and the potential application of dendrimer in imaging of plaque

Anwaier

Chen

Cao

et al. 2017

IJN

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Despite the fact that technological advancements have been made in diagnosis and treatment, cardiovascular diseases (CVDs) remain the leading cause of mortality and morbidity worldwide. Early detection of atherosclerosis (AS), especially vulnerable plaques, plays a crucial role in the prevention of acute coronary syndrome (ACS). Targeting the critical cytokines and molecules that are upregulated during the biological process of AS by in vivo molecular imaging has been widely used in plaque imaging. With their three-dimensional architecture, composition, and abundant terminal functional groups, dendrimers provide a platform for multitargeting and multimodal imaging. Thus, modified dendrimers with the key molecules upregulated in AS plaques will be an innovative attempt to achieve targeted imaging of AS plaques specifically and efficiently. This review was aimed to address some recent works on imaging of AS plaques using various types of image technology and further discuss the applications of dendrimers, an innovative yet seldom used method in imaging of AS plaques due to some limitations and challenges, and we highlight the bright future of the modified dendrimers in characterizing AS plaques.

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PEGylated dendrimer-entrapped gold nanoparticles for in vivo blood pool and tumor imaging by computed tomography

Cited by 367 publications

References 34 publications

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

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

Gold nanoparticles allow detection of early-stage edema in mice via computed tomography imaging

A review of molecular imaging of atherosclerosis and the potential application of dendrimer in imaging of plaque

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