scholarly journals Investigation of Specific Targeting of Triptorelin-Conjugated Dextran-Coated Magnetite Nanoparticles as a Targeted Probe in GnRH+ Cancer Cells in MRI

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Milad Yousefvand ◽  
Zahra Mohammadi ◽  
Farzaneh Ghorbani ◽  
Rasoul Irajirad ◽  
Hormoz Abedi ◽  
...  
Keyword(s):  
Contrast Agent ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Tumor Targeting ◽  
Tumor Imaging ◽  
Superparamagnetic Iron Oxide ◽  
Gnrh Receptors ◽  
Imaging Probes ◽  
Magnetic Resonance Imaging Mri ◽  
Targeted Contrast Agent

In recent years, the conjugation of superparamagnetic iron oxide nanoparticles (SPIONs), as tumor-imaging probes for magnetic resonance imaging (MRI), with tumor targeting peptides possesses promising advantages for specific delivery of MRI agents. The objective of the current study was to design a targeted contrast agent for MRI based on Fe3O4 nanoparticles conjugated triptorelin (SPION@triptorelin), which has a great affinity to the GnRH receptors. The SPIONs-coated carboxymethyl dextran (SPION@CMD) conjugated triptorelin (SPION@CMD@triptorelin) were synthesized using coprecipitation method and characterized by DLS, TEM, XRD, FTIR, Zeta, and VSM techniques. The relaxivities of synthetized formulations were then calculated using a 1.5 Tesla clinical magnetic field. MRI, quantitative cellular uptake, and cytotoxicity level of them were estimated. The characterization results confirmed that the formation of SPION@CMD@triptorelin has been conjugated with a suitable size. Our results demonstrated the lack of cellular cytotoxicity of SPION@CMD@triptorelin, and it could increase the cellular uptake of SPIONs to MDA-MB-231 cancer cells 6.50-fold greater than to SPION@CMD at the concentration of 75 μM. The relaxivity calculations for SPION@CMD@triptorelin showed a suitable r2 and r2/r1 with values of 31.75 mM−1·s−1 and 10.26, respectively. Our findings confirm that triptorelin-targeted SPIONs could provide a T2-weighted probe contrast agent that has the great potential for the diagnosis of GnRH-positive cancer in MRI.

scholarly journals Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

2018 ◽  
Vol 14 ◽  
pp. 756-771 ◽  
Author(s):  
Sabine Schuster ◽  
Beáta Biri-Kovács ◽  
Bálint Szeder ◽  
Viktor Farkas ◽  
László Buday ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Laser Scanning ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Dependent Manner ◽  
Binding Studies ◽  
Gnrh Receptors

Gonadotropin releasing hormone-III (GnRH-III), a native isoform of the human GnRH isolated from sea lamprey, specifically binds to GnRH receptors on cancer cells enabling its application as targeting moieties for anticancer drugs. Recently, we reported on the identification of a novel daunorubicin–GnRH-III conjugate (GnRH-III–[4Lys(Bu), 8Lys(Dau=Aoa)] with efficient in vitro and in vivo antitumor activity. To get a deeper insight into the mechanism of action of our lead compound, the cellular uptake was followed by confocal laser scanning microscopy. Hereby, the drug daunorubicin could be visualized in different subcellular compartments by following the localization of the drug in a time-dependent manner. Colocalization studies were carried out to prove the presence of the drug in lysosomes (early stage) and on its site of action (nuclei after 10 min). Additional flow cytometry studies demonstrated that the cellular uptake of the bioconjugate was inhibited in the presence of the competitive ligand triptorelin indicating a receptor-mediated pathway. For comparative purpose, six novel daunorubicin–GnRH-III bioconjugates have been synthesized and biochemically characterized in which 6Asp was replaced by D-Asp, D-Glu and D-Trp. In addition to the analysis of the in vitro cytostatic effect and cellular uptake, receptor binding studies with 125I-triptorelin as radiotracer and degradation of the GnRH-III conjugates in the presence of rat liver lysosomal homogenate have been performed. All derivatives showed high binding affinities to GnRH receptors and displayed in vitro cytostatic effects on HT-29 and MCF-7 cancer cells with IC50 values in a low micromolar range. Moreover, we found that the release of the active drug metabolite and the cellular uptake of the bioconjugates were strongly affected by the amino acid exchange which in turn had an impact on the antitumor activity of the bioconjugates.

scholarly journals Renal-clearable hyaluronic acid functionalized NaGdF4 nanodots with enhanced tumor accumulation

RSC Advances ◽  
2020 ◽  
Vol 10 (23) ◽  
pp. 13872-13878 ◽  
Author(s):  
Yining Yan ◽  
Lei Ding ◽  
Lin Liu ◽  
Murad M. A. Abualrejal ◽  
Hongda Chen ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Hyaluronic Acid ◽  
Magnetic Resonance ◽  
Contrast Agent ◽  
Tumor Targeting ◽  
Mri Contrast Agent ◽  
Resonance Imaging ◽  
Mri Contrast ◽  
Magnetic Resonance Imaging Mri ◽  
Tumor Accumulation

Hyaluronic acid functionalized NaGdF4 nanodots were synthesized and evaluated as an active tumor-targeting magnetic resonance imaging (MRI) contrast agent.

scholarly journals Glucosamine Conjugated Gadolinium (III) Oxide Nanoparticles as a Novel Targeted Contrast Agent for Cancer Diagnosis in MRI

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
T Mortezazadeh
Keyword(s):  
Magnetic Resonance ◽  
Contrast Agent ◽  
Tumor Cells ◽  
Glucose Transporter ◽  
Human Carcinomas ◽  
Magnetic Resonance Imaging Mri ◽  
Tumor Agent ◽  
Cell Glucose ◽  
Targeted Contrast Agent

Abstract Background: Glucose transporter (Glut), a cellular transmembrane receptor, has a key role in the metabolism of cell glucose and is also associated with various human carcinomas. Objective: In this study, we evaluated a magnetic resonance (MR) imaging contrast agent for tumor detection based on paramagnetic gadolinium oxide (Gd2O3) coated polycyclodextrin (PCD) and modified with glucose (Gd2O3@PCD-Glu) for the targeting of overexpressed glucose receptors. Material and Methods: In this experimental study, 3T magnetic resonance imaging (MRI) scanner was used to assess the specific interactions between Glut1-overexpressing tumor cells (MDA-MB-231) and Gd2O3@PCD-Glu NPs. Furthermore, the capacity of transporting Gd2O3@PCD-Glu NPs to tumor cells was evaluated. Results: It was found that the acquired MRI T1 signal intensity of MDA-MB-231 cells that were treated with the Gd2O3@PCD-Glu NPs increased significantly. Based on the results obtained, Gd2O3@PCD-Glu NPs can be applied in targeting Glut1-overexpressing tumor cells in vivo, as well as an MRI-targeted tumor agent to enhance tumor diagnosis. Conclusion: Results have shown that glucose-shell of magnetic nanoparticles has a key role in diagnosing cancer cells of high metabolic activity.

scholarly journals Preparation and Evaluation of New LAT1-Targeted USPION to Improve Sensitivity and Specificity in Metabolic Magnetic Imaging of Breast Cancer

2020 ◽  
Vol 11 (3) ◽  
pp. 10248-10264
Keyword(s):  
Breast Cancer ◽  
Contrast Agent ◽  
Cancer Cells ◽  
Cell Line ◽  
Sensitivity And Specificity ◽  
Cellular Uptake ◽  
Signal Intensity ◽  
Breast Cancer Cells ◽  
Blue Staining ◽  
Icp Oes

The purpose of this study was the investigation of the targeting potential of tyrosine-conjugated ultra small superparamagnetic iron oxide nanoparticles (USPIONs) as a new targeted nano-contrast agent for application in molecular magnetic resonance imaging (MRI) of breast cancer. Recently, studies demonstrated that L-type amino acid transporters (LAT1) are highly expressed in breast cancer cells. Thus, LAT1 targeting via tyrosine as a LAT1 substrate could improve the sensitivity and specificity of this nanosized contrast agent. To achieve this goal, USPIONs were conjugated to tyrosine and characterized using DLS and FT-IR. The cell viability was measured in different concentrations of nanoparticles (0.6, 1.2, 2.4mM) in breast cancer cells (MDA231, MCF7,4T1) and control cell line (normal kidney cells; HEK293) with the MTT assay. Cellular uptake was evaluated via Prussian blue staining and Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES) as well as by measurement of the reduction of signal intensity using 3Tesla clinical MRI. T2-weighted imaging in tumor-bearing bulb/c mice was performed via brain coil and home-built phantom. The particle size and charge of USPIO significantly changed after the conjugation of tyrosine. According to ICP-OES results from the cellular uptake of tyrosine-USPION in 4T1 cell line and HEK-293was 48.14%±1.43, and 6.91±0.21, respectively. The reduction in MRI signal intensity at in vitro studies was higher in the presence of tyrosine-USPION than of USPION. The reduction in MRI signal intensity at in vivo studies was 58.83% in the presence of tyrosine conjugated USPION compared with plain nanoparticles. Biodistribution studies demonstrated that the accumulation of tyrosine-USPIONs was about seven times higher than that of non-targeted USPIONs after 24h. In conclusion, tyrosine-USPIO as a new LAT1 targeted contrast agent with high sensitivity and specificity can be suggested as a good and ideal candidate in breast cancer molecular imaging.

A Low Molecular Weight Folate Receptor Targeted Contrast Agent for Magnetic Resonance Tumor Imaging

2010 ◽  
Vol 13 (4) ◽  
pp. 653-662 ◽  
Author(s):  
Tammy L. Kalber ◽  
Nazila Kamaly ◽  
Po-Wah So ◽  
John A. Pugh ◽  
Josephine Bunch ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Magnetic Resonance ◽  
Contrast Agent ◽  
Tumor Imaging ◽  
Folate Receptor ◽  
Low Molecular Weight ◽  
Targeted Contrast Agent

Tumor-Targeting Peptides: Ligands for Molecular Imaging and Therapy

2018 ◽  
Vol 18 (1) ◽  
pp. 74-86 ◽  
Author(s):  
Ning Zhao ◽  
Yeshan Qin ◽  
Hongguang Liu ◽  
Zhen Cheng
Keyword(s):  
Clinical Trials ◽  
Tumor Cells ◽  
Tumor Targeting ◽  
Tumor Imaging ◽  
Therapeutic Agents ◽  
Cure Rate ◽  
High Affinity ◽  
Tumor Diagnostics ◽  
Tumor Tissues ◽  
Imaging Probes

The aberrant proliferation of tumor cells and abundant vasculature in tumor tissues are closely correlated with receptors that are specifically dysregulated in tumor cells. These tumor-associated targets are critical in early diagnosis and therapy selection. Ligands such as antibodies, proteins, polypeptides and polysaccharides that specifically bind to these targets can significantly improve the detection and cure rate when used as tumor imaging probes or anti-tumor agents. Compared to other targeting ligands, peptides have attracted increasingly more attention in tumor diagnostics and therapeutics because of their small sizes, high affinity, stability, ease of modification and low immunogenicity. Several peptide-based imaging probes and therapeutic agents have already been used in clinical trials. This review summarizes some of the tumor-associated targets and their corresponding peptides, as well as the potential of these peptides in cancer treatment.

scholarly journals Design of an Amphiphilic Poly(aspartamide)-mediated Self-assembled Nanoconstruct for Long-Term Tumor Targeting and Bioimaging

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 885 ◽  
Author(s):  
Kondareddy Cherukula ◽  
Saji Uthaman ◽  
In-Kyu Park
Keyword(s):  
Cancer Cells ◽  
Targeted Delivery ◽  
Tumor Targeting ◽  
Tumor Imaging ◽  
Systemic Circulation ◽  
Systemic Clearance ◽  
Tumor Endothelium ◽  
Αvβ3 Integrins ◽  
Tumor Homing

Biodegradable polymers have been developed for the targeted delivery of therapeutics to tumors. However, tumor targeting and imaging are usually limited by systemic clearance and non-specific adsorption. In this study, we used poly(amino acid) derivatives, such as poly(succinimide), to synthesize a nanomicelle-forming poly(hydroxyethylaspartamide) (PHEA, P) modified sequentially with octadecylamine, polyethylene glycol (PEG, P), and glycine (G) to design PHEA-PEG-glycine (PPG) nanoparticles (NPs). These PPG NPs were further tethered to cyclic Arg-Gly-Asp (cRGD) sequences for formulating tumor-targeting PPG-cRGD NPs, and then loaded with IR-780 dye (PPG-cRGD-IR-780) for visualizing tumor homing. cRGD cloaked in PPG NPs could bind specifically to both tumor endothelium and cancer cells overexpressing αvβ3 integrins. PPG-cRGD NPs exhibited enhanced physiological stability, cellular viability, and targeted intracellular uptake in cancer cells. In addition, PPG-cRGD NPs offered enhanced systemic circulation, leading to preferential tumor targeting and prolonged fluorescence tumor imaging for nearly 30 days. Nevertheless, non-targeted formulations demonstrated premature systemic clearance with short-term tumor imaging. Histochemical analysis showed no damage to normal organs, reaffirming the biocompatibility of PHEA polymers. Overall, our results indicated that PPG-cRGD NPs, which were manipulated to obtain optimal particle size and surface charge, and were complemented with tumor targeting, could improve the targeted and theranostic potential of therapeutic delivery.

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