Synthesis and characterization of Bombesin-superparamagnetic iron oxide nanoparticles as a targeted contrast agent for imaging of breast cancer using MRI

Abstract

The targeted delivery of superparamagnetic iron oxide nanoparticles (SPIONs) as a contrast agent may facilitate their accumulation in cancer cells and enhance the sensitivity of MR imaging. In this study, SPIONs coated with dextran (DSPIONs) were conjugated with bombesin (BBN) to produce a targeting contrast agent for detection of breast cancer using MRI. X-ray diffraction, transmission electron microscopy, and vibrating sample magnetometer analyses indicated the formation of dextran-coated superparamagnetic iron oxide nanoparticles with an average size of 6.0 ± 0.5 nm. Fourier transform infrared spectroscopy confirmed the conjugation of the BBN with the DSPIONs. A stability study proved the high optical stability of DSPION-BBN in human blood serum. DSPION-BBN biocompatibility was confirmed by cytotoxicity evaluation. A binding study showed the targeting ability of DSPION-BBN to bind to T47D breast cancer cells overexpressing gastrin-releasing peptide (GRP) receptors. T2-weighted and T2*-weighted color map MR images were acquired. The MRI study indicated that the DSPION-BBN possessed good diagnostic ability as a GRP-specific contrast agent, with appropriate signal reduction in T2*-weighted color map MR images in mice with breast tumors.

Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment

“…These include: coupling to fluorescent-probes to be used for optical-imaging[66–68]; coupling to gold-nanorods coated with PEG which can be used for photoacoustical imaging for use particularly in breast-cancers idenfication[69]; conjugation to superparamagnetic iron oxide nanoparticles[70,71] or to other contrast agents[Gd-TTDA-NP, a protein based contrast agent, ProCA1] enhances detection by MRI; magnetofluorescent polymeric nanoparticles coupled to BnR-agonists improve the localization of the nanoparticles in PC-3 bearing mice compared to nanoparticles without coupling to a Bn-agonist, suggesting this approach could be useful for prostate-cancer imaging[72]; and the use of radiolabeled-monoclonal antibodies to proGRP to image tumors(gastric, lung) overexpressing Bn-related peptides.…”

“…Furthermore, recent studies also report a number of BnR-antagonists(primarily to GRPR) coupled to radioisotopes( 111 In) are highly effective at binding to breast-cancer-cells in vitro and imaging breast-cancers xenografts in vivo [111•]. BnR-agonists conjugated to superparamagnetic-iron-oxide nanoparticles, which function as a targeting contrast agent for MRI-imaging[70], retain high-affinity for the GRPR on breast-cancer-cells, and demonstrated good diagnostic ability to localize breast-cancer-xenografts in nude-mice[70]. A hybrid-probe combining a 99m Tc-labeled-BnR-agonist with a folate-receptor ligand, another receptor, which is frequently overexpressed in breast-cancers[80], was reported to show enhanced uptake in both in vitro studies with breast-cancer-cells and in breast-cancer- xenografts.…”

Scavenger Receptors

“…SR-A can efficiently mediate opsonin-independent internalization of dextran-coated superparamagnetic iron oxide (SPIO) nanoparticles via its positively charged extracellular collagenous domain (Chao et al, 2013, 2012). SPIO-based delivery platform may be used for early detection of metastases in cancer patients or used as a carrier to deliver chemotherapeutics into tumors (Chiang, Tseng, Liao, & Chen, 2015; Jafari et al, 2015). SR-A was shown to specifically express on the immunosuppressive vascular leukocytes (VCLs) in mouse and human ovarian cancer.…”

Lipase NS81006 immobilized on Fe3O4 magnetic nanoparticles for biodiesel production

“…For the naked-Fe3O4 magnetic nanoparticles, diffraction peaks at Bragg angles 2θ ~ 18°, 30°, 35°, 43°, 53°, 57° and 63° were identified, that are corresponded to the crystal planes of (111), (220), (311), (400), (422), (511) and (440) respectively. According to JCPDS card number 19-0629, these obtained peaks were related to Fe3O4 with an inverse spinel structure [21,22].…”