Breast Cancer Cells Imaging By Targeting Methionine Transporters with Gadolinium-Based Nanoprobe

Mehravi, Bita; Ardestani, Mehdi Shafiee; Damercheli, Maryam; Soltanghoraee, Haleh; Ghanaldarlaki, Negar; Alizadeh, Ali Mohammad; Oghabian, Mohammad Ali; Shirazi, Maryam Shahzad; Mahernia, Shabnam; Amanlou, Massoud

doi:10.1007/s11307-014-0718-3

Cited by 12 publications

(19 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The contrast agent 4-[(L-methionine)carbonyl]-2,2,6,6-tetraethylpiperidin-1-oxyl (TEEPO-Met, 5 ) was prepared by connecting TEEPO to methionine by an amide bond ( Scheme 1 ). The bonding site of methionine was chosen according to earlier studies [ 25 ]. The starting material, 4-oxo-2,2,6,6-tetraethylpiperidin-1-oxyl (4-oxo-TEEPO, 1 ) [ 26 ], was transformed to 4-carboxy-2,2,6,6-tetraethylpiperidin-1-oxyl (4-COOH-TEEPO, 3 ), via 4-carbonitrile-2,2,6,6-tetraethylpiperidin-1-oxyl (4-CN-TEEPO, 2 ) adapting a method by Studer et al [ 27 ].…”

Section: Resultsmentioning

confidence: 99%

“…Due to the increased amino acid uptake in tumours and its common use as a targeting radiotracer in PET, methionine was chosen as the targeting unit in this study. Also, the targeting abilities of methionine have already been studied by preparing targeting gadolinium-based nanoprobes for MRI [ 25 ]. This study comprises the synthesis of the new targeting unit and assessment of its stability by EPR spectroscopy as well as relaxation enhancing properties by in vitro NMR spectroscopy and a phantom MRI study.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis, Stability and Relaxivity of TEEPO-Met: An Organic Radical as a Potential Tumour Targeting Contrast Agent for Magnetic Resonance Imaging

et al. 2018

View full text Add to dashboard Cite

Cancer is a widespread and life-threatening disease and its early-stage diagnosis is vital. One of the most effective, non-invasive tools in medical diagnostics is magnetic resonance imaging (MRI) with the aid of contrast agents. Contrast agents that are currently in clinical use contain metals, causing some restrictions in their use. Also, these contrast agents are mainly non-specific without any tissue targeting capabilities. Subsequently, the interest has notably increased in the research of organic, metal-free contrast agents. This study presents a new, stable organic radical, TEEPO-Met, where a radical moiety 2,2,6,6-tetraethylpiperidinoxide (TEEPO) is attached to an amino acid, methionine (Met), as a potentially tumour-targeting moiety. We describe the synthesis, stability assessment with electron paramagnetic resonance (EPR) spectroscopy and relaxation enhancement abilities by an in vitro nuclear magnetic resonance (NMR) and phantom MRI studies of TEEPO-Met. The new compound proved to be stable notably longer than the average imaging time in conditions mimicking a biological matrix. Also, it significantly reduced the relaxation times of water, making it a promising candidate as a novel tumour targeting contrast agent for MRI.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis, Stability and Relaxivity of TEEPO-Met: An Organic Radical as a Potential Tumour Targeting Contrast Agent for Magnetic Resonance Imaging

et al. 2018

View full text Add to dashboard Cite

show abstract

“…CTAB was removed according to a previously reported procedure by simple modification 37. Briefly, a mixture of NH 4 NO 3 (10 mg/mL) and MSNs (1 mg/mL) was refluxed at 80°C for 6 hours under N 2 gas atmosphere.…”

Section: Methodsmentioning

confidence: 99%

Mesoporous silica nanoparticles functionalized with folic acid/methionine for active targeted delivery of docetaxel

Khosravian¹,

Ardestani²,

Khoobi³

et al. 2016

OTT

Self Cite

View full text Add to dashboard Cite

Mesoporous silica nanoparticles (MSNs) are known as carriers with high loading capacity and large functionalizable surface area for target-directed delivery. In this study, a series of docetaxel-loaded folic acid- or methionine-functionalized mesoporous silica nanoparticles (DTX/MSN-FA or DTX/MSN-Met) with large pores and amine groups at inner pore surface properties were prepared. The results showed that the MSNs were successfully synthesized, having good pay load and pH-sensitive drug release kinetics. The cellular investigation on MCF-7 cells showed better performance of cytotoxicity and cell apoptosis and an increase in cellular uptake of targeted nanoparticles. In vivo fluorescent imaging on healthy BALB/c mice proved that bare MSN-NH2 are mostly accumulated in the liver but MSN-FA or MSN-Met are more concentrated in the kidney. Importantly, ex vivo fluorescent images of tumor-induced BALB/c mice organs revealed the ability of MSN-FA to reach the tumor tissues. In conclusion, DTX/MSNs exhibited a good anticancer activity and enhanced the possibility of targeted drug delivery for breast cancer.

show abstract

“…Hence, to gain more understanding, we chose glucosamine which is similar to 2-deoxyglucose and can be taken up by GLUT receptors 24 and methionine that can be taken up by amino acid transporters, 25,26 and conjugated them to three well-studied aromatic dinitrobenzoate mustards, reported by Denny, Wilson and co-workers. 27,28 These mustards are known to be more active under hypoxic condition [29][30][31][32][33][34] with various advanced techniques viz., gene directed enzyme prodrug therapy (GDEPT) and antibody directed enzyme prodrug therapy (ADEPT).…”

Section: Introductionmentioning

confidence: 99%

Effect of methionine and glucosamine conjugation on the anticancer activity of aromatic dinitrobenzamide mustards

2016

View full text Add to dashboard Cite

Certain nutrients viz., glucose and methionine are consumed more by cancer cells. Hence, an anticancer agent conjugated to them may render more toxicity in cancer cells due to higher uptake. To probe this effect, methionine and glucosamine were conjugated to a series of well-known aromatic dinitrobenzamide mustards. The in vitro cytotoxicity studies performed to probe the effect of such conjugation showed that the conjugation of methionine and glucosamine to one of the dinitrobenzamide mustard led to more toxicity selectively in human breast adenocarcinoma (MCF-7) cell lines. However, effect of functionalization cannot be generalized. Hypoxia based studies showed that IC 50 value did not show much change from normoxic condition which is encouraging as many drugs deactivate in hypoxia. Among the glucosamine and methionine conjugated dinitrobenzamide mustards, the methionine conjugated aromatic dinitrobenzamide mustard of 2-chlorobenzoic acid is the most effective one. It acts by inducing apoptosis through G2/M phase arrest and encouragingly, is much less toxic to nontumorigenic human embryonic kidney (HEK-293T) and mouse embryonic fibroblast (NIH 3T3) cell lines in vitro.

show abstract

Breast Cancer Cells Imaging By Targeting Methionine Transporters with Gadolinium-Based Nanoprobe

Abstract: The results showed that the novel contrast agent could become a useful tool in early detection of cancer.

Cited by 12 publications

References 26 publications

Synthesis, Stability and Relaxivity of TEEPO-Met: An Organic Radical as a Potential Tumour Targeting Contrast Agent for Magnetic Resonance Imaging

Synthesis, Stability and Relaxivity of TEEPO-Met: An Organic Radical as a Potential Tumour Targeting Contrast Agent for Magnetic Resonance Imaging

Mesoporous silica nanoparticles functionalized with folic acid/methionine for active targeted delivery of docetaxel

Effect of methionine and glucosamine conjugation on the anticancer activity of aromatic dinitrobenzamide mustards

Contact Info

Product

Resources

About