Sugar/gadolinium-loaded gold nanoparticles for labelling and imaging cells by magnetic resonance imaging

Irure, Ainhoa; Marradi, Marco; Arnáiz, Blanca; Genicio, Nuria; Padró, Daniel; Penadés, Soledad

doi:10.1039/c3bm60032g

Cited by 47 publications

(41 citation statements)

References 75 publications

(99 reference statements)

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“…18,20,21,24 Our group previously devised cell permeable, Gd(III)-enriched DNA–gold nanoparticle conjugates (DNA-Gd(III)@AuNPs) for cellular T 1 -weighted MR imaging. 21 These constructs demonstrated high stability, cellular uptake, and surface loading of Gd(III).…”

Section: Introductionmentioning

confidence: 99%

Gd(III)-Gold Nanoconjugates Provide Remarkable Cell Labeling for High Field Magnetic Resonance Imaging

et al. 2016

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In vivo cell tracking is vital for understanding migrating cell populations, particularly cancer and immune cells. Magnetic resonance (MR) imaging for long-term tracking of transplanted cells in live organisms requires cells to effectively internalize Gd(III) contrast agents (CAs). Clinical Gd(III)-based CAs require high dosing concentrations and extended incubation times for cellular internalization. To combat this, we have devised a series of Gd(III)-gold nanoconjugates (Gd@AuNPs) with varied chelate structure and nanoparticle-chelate linker length, with the goal of labeling and imaging breast cancer cells. These new Gd@AuNPs demonstrate significantly enhanced labeling compared to previous Gd(III)-gold-DNA nanoconstructs. Variations in Gd(III) loading, surface packing, and cell uptake were observed among four different Gd@AuNP formulations suggesting that linker length and surface charge play an important role in cell labeling. The best performing Gd@AuNPs afforded 23.6 ± 3.6 fmol of Gd(III) per cell at an incubation concentration of 27.5 μM—this efficiency of Gd(III) payload delivery (Gd(III)/cell normalized to dose) exceeds that of previous Gd(III)-Au conjugates and most other Gd(III)-nanoparticle formulations. Further, Gd@AuNPs were well-tolerated in vivo in terms of biodistribution and clearance, and supports future cell tracking applications in whole-animal models.

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Section: Introductionmentioning

confidence: 99%

Gd(III)-Gold Nanoconjugates Provide Remarkable Cell Labeling for High Field Magnetic Resonance Imaging

et al. 2016

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“…[ 30,31 ] IgG anti-human CD71 was purchased from R&D systems, HBSS (Hanks' balanced salt solution) and growth media RPMI-1640 were obtained from Gibco. Ficoll-Paque was obtained from GE Healthcare.…”

Section: Methodsmentioning

confidence: 99%

“…Glycoconjugates of β -lactose ( lac C 5 SH) and α -mannose ( man C 2 NH 2 ) having a thiol-ending fi ve aliphatic linker and an amino ethyl linker, respectively, have been synthesized as already described. [ 30,31 ] They were also used as capping agents for the preparation of the corresponding glycoQDs (Scheme 1 ).…”

Section: Synthesis and Properties Of Cdte-based Quantum Dotsmentioning

confidence: 99%

CdTe‐Based QDs: Preparation, Cytotoxicity, and Tumor Cell Death by Targeting Transferrin Receptor

Gallo

Garcı́a

Genicio

et al. 2013

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In the past few years, quantum dots have attracted great attention owing to their unique photoluminescent properties. One of the most promising fields of application for QDs is biomedicine, but for any application in this area, the nanocrystals have to be water soluble, biocompatible and should emit in the near‐infrared region. As “traditional” QDs preparations rely on wet chemistry reactions on non‐polar solvents, an extra step must be introduced to render the nanocrystals soluble in the aqueous media. This extra step can reduce the quality of the final QDs. Direct preparations of CdTe‐based QDs in water are developed to overcome this problem. Here, the preparation in water of red‐emitting CdTe‐based QDs coated with different organic ligands, including sugar conjugates is presented. The viability of human cell lines in their presence is assessed. A red‐emitting QD is further functionalized with proteins and antibodies to demonstrate their in vitro potential for targeting and killing cancer cells.

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“…The basic structures and gadolinium content of each Gd-GNP type are schematized in Figure 1 and listed in Table 1. The Gd-GNPs were prepared by ligand place exchange reaction (LPE) starting from glyconanoparticles (GNPs) coated only with sugars as described in [13,31] (Gd-GNPs E_1, E_2 and F-J). The sugars (glucose, galactose) are conjugated to an aliphatic chain of variable number of carbon atoms (C2, C3, C5, C7, C9, C11), while the DO3A derivatives contain a C11 aliphatic chain (Table 1).…”

Section: Methodsmentioning

confidence: 99%

“…This method should be a better predictor of in vivo performance than classic in vitro relaxivity measurements. To validate it, we have tested novel paramagnetic Gd-based gold nanoparticles (Gd-GNPs) (Figure 1) [7,13] as well as superparamagnetic iron oxide nanoparticles (SPIONs) [14]. The Gd-GNPs incorporate several copies of sugars (which confer biocompatibility and water solubility) and Gd complexes.…”

Section: Introductionmentioning

confidence: 99%

A new ex vivo method to evaluate the performance of candidate MRI contrast agents: a proof-of-concept study

et al. 2014

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BackgroundMagnetic resonance imaging (MRI) plays an important role in tumor detection/diagnosis. The use of exogenous contrast agents (CAs) helps to improve the discrimination between lesion and neighbouring tissue, but most of the currently available CAs are non-specific. Assessing the performance of new, selective CAs requires exhaustive assays and large amounts of material. Accordingly, in a preliminary screening of new CAs, it is important to choose candidate compounds with good potential for in vivo efficiency. This screening method should reproduce as close as possible the in vivo environment. In this sense, a fast and reliable method to select the best candidate CAs for in vivo studies would minimize time and investment cost, and would benefit the development of better CAs.ResultsThe post-mortem ex vivo relative contrast enhancement (RCE) was evaluated as a method to screen different types of CAs, including paramagnetic and superparamagnetic agents. In detail, sugar/gadolinium-loaded gold nanoparticles (Gd-GNPs) and iron nanoparticles (SPIONs) were tested. Our results indicate that the post-mortem ex vivo RCE of evaluated CAs, did not correlate well with their respective in vitro relaxivities. The results obtained with different Gd-GNPs suggest that the linker length of the sugar conjugate could modulate the interactions with cellular receptors and therefore the relaxivity value. A paramagnetic CA (GNP (E_2)), which performed best among a series of Gd-GNPs, was evaluated both ex vivo and in vivo. The ex vivo RCE was slightly worst than gadoterate meglumine (201.9 ± 9.3% versus 237 ± 14%, respectively), while the in vivo RCE, measured at the time-to-maximum enhancement for both compounds, pointed to GNP E_2 being a better CA in vivo than gadoterate meglumine. This is suggested to be related to the nanoparticule characteristics of the evaluated GNP.ConclusionWe have developed a simple, cost-effective relatively high-throughput method for selecting CAs for in vivo experiments. This method requires approximately 800 times less quantity of material than the amount used for in vivo administrations.

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Sugar/gadolinium-loaded gold nanoparticles for labelling and imaging cells by magnetic resonance imaging

Cited by 47 publications

References 75 publications

Gd(III)-Gold Nanoconjugates Provide Remarkable Cell Labeling for High Field Magnetic Resonance Imaging

Gd(III)-Gold Nanoconjugates Provide Remarkable Cell Labeling for High Field Magnetic Resonance Imaging

CdTe‐Based QDs: Preparation, Cytotoxicity, and Tumor Cell Death by Targeting Transferrin Receptor

A new ex vivo method to evaluate the performance of candidate MRI contrast agents: a proof-of-concept study

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