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

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.

Polydopamine-Coated Laponite Nanoplatforms for Photoacoustic Imaging-Guided Chemo-Phototherapy of Breast Cancer

Theranostic nanoplatforms combining photosensitizers and anticancer drugs have aroused wide interest due to the real-time photoacoustic (PA) imaging capability and improved therapeutic efficacy by the synergistic effect of chemotherapy and phototherapy. In this study, polydopamine (PDA) coated laponite (LAP) nanoplatforms were synthesized to efficiently load indocyanine green (ICG) and doxorubicin (DOX), and modified with polyethylene glycol-arginine-glycine-aspartic acid (PEG-RGD) for PA imaging-guided chemo-phototherapy of cancer cells overexpressing αvβ3 integrin. The formed ICG/LAP-PDA-PEG-RGD/DOX nanoplatforms showed significantly higher photothermal conversion efficiency than ICG solution and excellent PA imaging capability, and could release DOX in a pH-sensitive and NIR laser-triggered way, which is highly desirable feature in precision chemotherapy. In addition, the ICG/LAP-PDA-PEG-RGD/DOX nanoplatforms could be uptake by cancer cells overexpressing αvβ3 integrin with high specificity, and thus serve as a targeted contrast agent for in vivo PA imaging of cancer. In vivo experiments with 4T1 tumor-bearing mouse model demonstrated that ICG/LAP-PDA-PEG-RGD/DOX nanoplatforms exhibited much stronger therapeutic effect and higher survival rate than monotherapy due to the synergetic chemo-phototherapy under NIR laser irradiation. Therefore, the reported ICG/LAP-PDA-PEG-RGD/DOX represents a promising theranostic nanoplatform for high effectiveness PA imaging-guided chemo-phototherapy of cancer cells overexpressing αvβ3 integrin.

Citric acid coated ultrasmall superparamagnetic iron oxide nanoparticles conjugated with lactoferrin for targeted negative MR imaging of glioma

The proposed study was to develop the preparation of ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) modified with citric acid, with surface conjugated with lactoferrin (Lf), which used as a potential targeted contrast agent for magnetic resonance imaging (MRI) of brain glioma. USPIONs were prepared by the thermal decomposition method. The hydrophobic USPIONs were coated with citric acid by the ligand exchange method. Then, Lf was conjugated into the surface of USPIONs. The obtained Lf-USPIONs were analyzed by fourier transform infrared (FTIR) spectroscopy and polyacrylamide gel electrophoresis. The size, size distribution, shape and superparamagnetic property of Lf-USPIONs were investigated with TEM and vibrating sample magnetometer (VSM). Both FTIR and electrophoresis analysis demonstrated the successful conjugation of Lf to the surface of USPIONs. The average size of Lf-USPIONs was about 8.4 ± 0.5 nm, which was determined using the statistics of measured over 100 nanoparticles in the TEM image, with a negative charge of −7.3 ± 0.2 mV. TEM imaging revealed that Lf-USPIONs were good in dispersion and polygonal in morphology. VSM results indicated that Lf-USPIONs were superparamagnetic and the saturated magnetic intensity was about 69.8 emu/g. The Lf-USPIONs also showed good biocompatibility in hemolysis, cytotoxicity, cell migration and blood biochemistry studies. MR imaging results in vitro and in vivo indicated that Lf-USPIONs exhibited good negative contrast enhancement. Taken together, Lf-USPIONs hold great potential for brain gliomas MR imaging as a nanosized targeted contrast agent.

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

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.

Molecular Ultrasound Imaging of the Spinal Cord for the Detection of Acute Inflammation

Molecular ultrasound imaging provides the ability to detect physiologic processes non-invasively by targeting a wide variety of biological markers in vivo. The current study investigates the novel application of molecular ultrasound imaging for the detection of neural inflammation. Using a murine model with acutely injured spinal cords (n=31), subjects were divided into four groups, each being administered ultrasound contrast microbubbles bearing antibodies against various known inflammatory molecules (P-selectin, vascular cell adhesion protein 1 [VCAM-1], intercellular adhesion molecule 1 [ICAM-1], and isotype control) during molecular ultrasound imaging. Upon administration of the targeted contrast agent, ultrasound imaging of the injured spinal cord was performed at 40MHz for seven minutes, followed by a bursting pulse. We observed significantly enhanced signals from contrast targeted to P-selectin and VCAM-1, using a variety of outcome measures. These findings provide preclinical evidence that molecular ultrasound imaging could be a useful tool in the detection of neural inflammation.