Magnetic resonance imaging, gadolinium neutron capture therapy, and tumor cell detection using ultrasmall Gd2O3 nanoparticles coated with polyacrylic acid-rhodamine B as a multifunctional tumor theragnostic agent

Ho, Son Long; Cha, Hyunsil; Oh, In Taek; Jung, Kim Mi; Kim, Mi Hyun; Lee, Yong Jin; Xu, Miao; Tegafaw, Tirusew; Ahmad, Mohammad Yaseen; Chae, Kwon Seok; Chang, Yongmin; Lee, Gang Ho

doi:10.1039/c8ra00553b

Cited by 44 publications

(17 citation statements)

References 75 publications

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“…These NPs colloids were applied to Gd-NCT in vitro and exhibited a significant U87MG tumor cell death (28.1% net value) after thermal neutron beam irradiation, which was 1.75 times higher than that obtained using commercial Gadovist. These colloids also exhibited stronger fluorescent intensities in tumor cells than in normal cells owing to conjugated Rho, proving their pH-sensitive fluorescent tumor cell detection ability (Figure 4) [135]. Jang and coworkers synthesized poly(acrylic acid-co-maleic acid) (PAAMA) coated Gd-NPs (d avg = 1.8 nm), which exhibited outstanding colloidal stability, exceptionally low cellular toxicity, and a high r 1 value of 40.6 s −1 •mM −1 and r 2 /r 1 ratio of 1.56, which is approximately 10 fold higher than those of commercial molecular CAs [136].…”

Section: Synthetic Polymersmentioning

confidence: 91%

Section: Functionalization Of Gd-npsmentioning

confidence: 99%

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Recent Advances in Gadolinium Based Contrast Agents for Bioimaging Applications

et al. 2021

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Gadolinium (Gd) based contrast agents (CAs) (Gd-CAs) represent one of the most advanced developments in the application of Gd for magnetic resonance imaging (MRI). Current challenges with existing CAs generated an urgent requirement to develop multimodal CAs with good biocompatibility, low toxicity, and prolonged circulation time. This review discussed the Gd-CAs used in bioimaging applications, addressing their advantages and limitations. Future research is required to establish the safety, efficacy and theragnostic capabilities of Gd-CAs. Nevertheless, these Gd-CAs offer extraordinary potential as imaging CAs and promise to benefit bioimaging applications significantly.

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Section: Synthetic Polymersmentioning

confidence: 91%

Section: Functionalization Of Gd-npsmentioning

confidence: 99%

Recent Advances in Gadolinium Based Contrast Agents for Bioimaging Applications

et al. 2021

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“…Generally, there are two protocols for the synthesis of inorganic Gd 3+ NDs: (1) direct synthesis of hydrophilic Gd 3+ NDs in water or polyol using a stabilizing agent which allows for crystal growth, followed by ligand exchange with a more robust stabilizing agent to improve the colloidal stability of Gd 3+ NDs in complex matrixes [62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81], and (2) preparation of hydrophobic Gd 3+ NDs in high boiling organic solvents by the pyrolysis methods, and subsequent transfer of the hydrophobic Gd 3+ NDs into aqueous phase by using a hydrophilic/amphiphilic ligand to render them water-dispersible [82][83][84][85][86][87][88][89][90] 6) [69]. Because the magnetic dipole interaction between surface Gd 3+ and 1 H is impeded by the PAA, both r 1 and r 2 values of Gd 2 O 3 NDs are decreased with increasing the molecular weight of PAA (Mw = 1200, 5100 and 15,000 Da).…”

Section: Gadolinium Nanodotsmentioning

confidence: 99%

“…Both r1 and r2 of the DEG capped Gd2O3 NDs are approximately 2 times higher than those of Gd-DTPA. Lee's group developed a one-pot synthesis method with two steps for preparing a series of hydrophilic Gd2O3 NDs with high colloidal stability: (1) using GdCl3•6H2O as Gd 3+ as precursors, Gd2O3 NDs were firstly synthesized in tripropylene/triethylene glycol (TPG/TEG) under alkaline condition, and aged by H2O2 and/or an O2 flow; (2) the as-prepared Gd2O3 NDs were then stabilized by different coating materials including amino acid, polymers, and carbon [63][64][65][66][67][68][69][70]. As early as 2009, Lee and coauthors synthesized D-glucuronic acid coated Gd2O3 NDs in TPG by using D-glucuronic acid as stabilizer [63].…”

Section: Gadolinium Nanodotsmentioning

confidence: 99%

The Renal Clearable Magnetic Resonance Imaging Contrast Agents: State of the Art and Recent Advances

Sun

2020

Molecules

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The advancements of magnetic resonance imaging contrast agents (MRCAs) are continuously driven by the critical needs for early detection and diagnosis of diseases, especially for cancer, because MRCAs improve diagnostic accuracy significantly. Although hydrophilic gadolinium (III) (Gd3+) complex-based MRCAs have achieved great success in clinical practice, the Gd3+-complexes have several inherent drawbacks including Gd3+ leakage and short blood circulation time, resulting in the potential long-term toxicity and narrow imaging time window, respectively. Nanotechnology offers the possibility for the development of nontoxic MRCAs with an enhanced sensitivity and advanced functionalities, such as magnetic resonance imaging (MRI)-guided synergistic therapy. Herein, we provide an overview of recent successes in the development of renal clearable MRCAs, especially nanodots (NDs, also known as ultrasmall nanoparticles (NPs)) by unique advantages such as high relaxivity, long blood circulation time, good biosafety, and multiple functionalities. It is hoped that this review can provide relatively comprehensive information on the construction of novel MRCAs with promising clinical translation.

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“…6 Moreover, there is a shift in paradigm towards combining the MRI contrast agent capabilities with other diagnostic or even therapeutic functions, leading to the so-called 'theranostic agents'. 7,8 The first nanoparticle-based contrast agent approved by the FDA was represented by superparamagnetic iron oxide nanoparticles (SPION), 9,10 although they have been largely replaced by contrast agents based on Gd. 11 Both classes have an effect of reduction in T 1 relaxation times, 12 but the use of contrast agents with T 2 sequences is limited.…”

Section: Introductionmentioning

confidence: 99%

Assessment of Gold-Coated Iron Oxide Nanoparticles as Negative T2 Contrast Agent in Small Animal MRI Studies

Iancu¹,

Albu²,

Chiriac³

et al. 2020

IJN

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Purpose: Magnetic resonance imaging (MRI) contrast agents are pharmaceuticals that enable a better visualization of internal body structures. In this study, we present the synthesis, MRI signal enhancement capabilities, in vitro as well as in vivo cytotoxicity results of gold-coated iron oxide nanoparticles (Fe 3 O 4 @AuNPs) as potential contrast agents. Methods: Fe 3 O 4 @AuNPs were obtained by synthesizing iron oxide nanoparticles and gradually coating them with gold. The obtained Fe 3 O 4 @AuNPs were characterized by spectroscopies, transmission electron microscopy (TEM) and energy dispersive X-ray diffraction. The effect of the nanoparticles on the MRI signal was tested using a 7T Bruker PharmaScan system. Cytotoxicity tests were made in vitro on Fe 3 O 4 @AuNP-treated retinal pigment epithelium cells by WST-1 tests and in vivo by following histopathological changes in rats after injection of Fe 3 O 4 @AuNPs. Results: Stable Fe 3 O 4 @AuNPs were successfully prepared following a simple and fast protocol (<1h worktime) and identified using TEM. The cytotoxicity tests on cells have shown biocompatibility of Fe 3 O 4 @AuNPs at small concentrations of Fe (<1.95×10 −8 mg/ cell). Whereas, at higher Fe concentrations (eg 7.5×10 −8 mg/cell), cell viability decreased to 80.88±5.03%, showing a mild cytotoxic effect. MRI tests on rats showed an optimal Fe 3 O 4 @AuNPs concentration of 6mg/100g body weight to obtain high-quality images. The histopathological studies revealed significant transient inflammatory responses in the time range from 2 hours to 14 days after injection and focal cellular alterations in several organs, with the lung being the most affected organ. These results were confirmed by hyperspectral microscopic imaging of the same, but unstained tissues. In most organs, the inflammatory responses and sublethal cellular damage appeared to be transitory, except for the kidneys, where the glomerular damage indicated progression towards glomerular sclerosis. Conclusion: The obtained stable, gold covered, iron oxide nanoparticles with reduced cytotoxicity, gave a negative T 2 signal in the MRI, which makes them suitable for candidates as contrast agent in small animal MRI applications.

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Magnetic resonance imaging, gadolinium neutron capture therapy, and tumor cell detection using ultrasmall Gd₂O₃ nanoparticles coated with polyacrylic acid-rhodamine B as a multifunctional tumor theragnostic agent

Abstract: Ultrasmall Gd2O3 nanoparticle colloids coated with PAA and Rho-PAA were synthesized and applied to T1 MRI, GdNCT and fluorescent tumor cell detection.

Cited by 44 publications

References 75 publications

Recent Advances in Gadolinium Based Contrast Agents for Bioimaging Applications

Recent Advances in Gadolinium Based Contrast Agents for Bioimaging Applications

The Renal Clearable Magnetic Resonance Imaging Contrast Agents: State of the Art and Recent Advances

<p>Assessment of Gold-Coated Iron Oxide Nanoparticles as Negative T2 Contrast Agent in Small Animal MRI Studies</p>

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