LHRH-conjugated Magnetic Iron Oxide Nanoparticles for Detection of Breast Cancer Metastases

Leuschner, Carola; Kumar, Challa S. S. R.; Hansel, William; Soboyejo, W. O.; Zhou, Jianxin; Hormes, J.

doi:10.1007/s10549-006-9199-7

Cited by 159 publications

(117 citation statements)

References 63 publications

(96 reference statements)

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“…The residue was dissolved in distilled water (10 ml) and precipitated by addition of acetone to give GdDOTA (1.34 g, 2.31 mmol, 94%) as a colorless solid. MALDI-MS: m/z calcd for C 16 …”

Section: Synthesismentioning

confidence: 99%

“…There is a great deal of interest in enhancing the utility of these tools in medicine and research through the development of molecularly-targeted MRI contrast agents. One example might be a chimeric molecule comprised of a contrast agent tethered to a molecule capable of binding to a specific protein or other biomolecular target with high affinity and specificity [4][5][6][7][8][9][10][11][12][13][14][15][16][17]. For example, we previously reported that a peptide selected from a phage display library to bind the yeast Gal80 protein can be linked to GdDOTA to create a reagent capable of imaging Gal80 protein in vitro [18,19].…”

Section: Introductionmentioning

confidence: 99%

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The detection limit of a Gd3+-based T1 agent is substantially reduced when targeted to a protein microdomain

Hanaoka

Lubag

Castillo-Muzquiz³

et al. 2008

Magnetic Resonance Imaging

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Simple low MW chelates of Gd 3+ such as those currently used in clinical MR imaging are considered too insensitive for most molecular imaging applications. Here, we evaluated the detection limit of a molecularly targeted, low MW Gd 3+ -based, T 1 agent in a model where the receptor concentration was precisely known. The data demonstrate that receptors clustered together to form a microdomain of high local concentration can be imaged successfully even when the bulk concentration of the receptor is quite low. A GdDO3A-peptide identified by phage display to target the anti-FLAG antibody was synthesized, purified and characterized. T 1 weighted MR images were compared with the agent bound to antibody in bulk solution and with the agent bound to the antibody localized on agarose beads. Fluorescence competition binding assays show that the agent has a high binding affinity (K D = 150 nM) for the antibody while the fully bound relaxivity of the GdDO3A-peptide:anti-FLAG antibody in solution was a relatively modest 17 mM −1 s −1 . The agent:antibody complex was MR silent at concentrations below ~9 µM but was detectable down to 4 µM bulk concentrations when presented to antibody clustered together on the surface of agarose beads. These results provided an estimate of the detection limits for other T 1 -based agents with higher fully bound relaxivities or multimeric structures bound to clustered receptor molecules. The results demonstrate that the sensitivity of molecularly-targeted contrast agents depends on the local microdomain concentration of the target protein and the molecular relaxivity of the bound complex. A model is presented which predicts that for a molecularly targeted agent consisting of a single Gd 3+ complex with bound relaxivity of 100 mM −1 s −1 or, more reasonably, four tethered Gd 3+ complexes each having a bound relaxivity of 25 mM −1 s −1 , the detection limit of a protein microdomain is ~690 nM at 9.4T. These experimental and extrapolated detection limits are both well below current literature estimates and suggests that detection of low MW molecularly targeted T 1 agents is not an unrealistic goal.

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“…The residue was dissolved in distilled water (10 ml) and precipitated by addition of acetone to give GdDOTA (1.34 g, 2.31 mmol, 94%) as a colorless solid. MALDI-MS: m/z calcd for C 16 …”

Section: Synthesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The detection limit of a Gd3+-based T1 agent is substantially reduced when targeted to a protein microdomain

Hanaoka

Lubag

Castillo-Muzquiz³

et al. 2008

Magnetic Resonance Imaging

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“…Importantly, the in vivo study showed that the LHRHSPIONs nanoparticle system did not accumulate in the livers of normal mice, suggesting that off-target effects were limited. By contrast, the non-targeted controls accumulated in the liver, making this study one of the best examples of successful selection of specific cancer cells by nanoparticles [52].…”

Section: Breast Cancer Selectionmentioning

confidence: 98%

“…For localised breast cancer selection, another important molecular marker is luteinising hormone-releasing hormone (LHRH) receptor on breast cancer cells. A superparamagnetic iron oxide nanoparticle (SPIONs) based system has been developed for detection of breast cancer metastasis (LHRH-conjugated magnetic iron oxide nanoparticles) [52]. Importantly, the in vivo study showed that the LHRHSPIONs nanoparticle system did not accumulate in the livers of normal mice, suggesting that off-target effects were limited.…”

Section: Breast Cancer Selectionmentioning

confidence: 99%

The potential legacy of cancer nanotechnology: cellular selection

Patra

Turner

2014

Trends in Biotechnology

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Overexpression of oncogenes or loss of tumour suppressors can transform a normal cell to a cancerous one, resulting in uncontrolled regulation of intracellular signaling pathways and immunity to stresses, which both pose therapeutic challenges.Conventional approaches to cancer therapy, although they are effective at killing cancer cells, may still fail due to inadequate biodistribution and unwanted side effects.Nanotechnology-based approaches provide a promising alternative, with the possibility of targeting cells at an early stage, during their transformation into cancer cells. This review considers techniques that specifically target those molecular changes, which begin in only a very small percentage of normal cells as they undergo transformation. These techniques are crucial for 'early-stage' diagnosis and therapy.3

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“…Recently, different types of nanoparticles-based therapeutic and diagnostic agents have been extensively studied to prolong the half-life of drug systemic circulation by reducing immunogenicity, sustained release of drugs in an environmentally responsive manner, lower frequency of administration in order to minimize systemic side effects of drugs for treatment of diabetes [1,2], asthma [3][4][5], allergy [6], infections [7,8], cardiovascular diseases [9], neurological diseases [10], cancers [11,12], pain, and so on. Therefore, a few pioneering therapeutic nanoparticles have been introduced into the pharmaceutical market.…”

Section: Introductionmentioning

confidence: 99%

Controlled-release formulation of perindopril erbumine loaded PEG-coated magnetite nanoparticles for biomedical applications

et al. 2014

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Iron oxide nanoparticles (FNPs) were synthesized due to low toxicity and their ability to immobilize biological materials on their surfaces by the coprecipitation of iron salts in ammonia hydroxide followed by coating it with polyethylene glycol (PEG) to minimize the aggregation of iron oxide nanoparticles and enhance the effect of nanoparticles for biological applications. Then, the FNPs-PEG was loaded with perindopril erbumine (PE), an antihypertensive compound to form a new nanocomposite (FPEGPE). Transmission electron microscopy results showed that there are no significant differences between the sizes of FNPs and FPEGPE nanocomposite. The existence of PEG-PE was supported by the FTIR and TGA analyses. The PE loading (10.3 %) and the release profiles from FPEGPE nanocomposite were estimated using ultraviolet-visible spectroscopy which showed that up to 60.8 and 83.1 % of the adsorbed drug was released in 4223 and 1231 min at pH 7.4 and 4.8, respectively. However, the release of PE was completed very fast from a physical mixture (FNPs-PEG-PE) after 5 and 7 min at pH 4.8 and 7.4, respectively, which reveals that the release of PE from the physical mixture is not in the sustained-release manner. Cytotoxicity study showed that free PE presented slightly higher toxicity than the FNPs and FPEGPE nanocomposite. Therefore, the decrease toxicity against mouse normal fibroblast (3T3) cell lines prospective of this nanocomposite together with controlled-release behavior provided evidence of the possible beneficial biological activities of this new nanocomposite for nanopharmaceutical applications for both oral and non-oral routes.

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LHRH-conjugated Magnetic Iron Oxide Nanoparticles for Detection of Breast Cancer Metastases

Cited by 159 publications

References 63 publications

The detection limit of a Gd3+-based T1 agent is substantially reduced when targeted to a protein microdomain

The detection limit of a Gd3+-based T1 agent is substantially reduced when targeted to a protein microdomain

The potential legacy of cancer nanotechnology: cellular selection

Controlled-release formulation of perindopril erbumine loaded PEG-coated magnetite nanoparticles for biomedical applications

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