Article

Combined magnetic resonance and optical imaging of head and neck tumor xenografts using Gadolinium-labelled phosphorescent polymeric nanomicelles.

Institute for Lasers, Photonics and Biophotonics, SUNY at Buffalo, Buffalo, New York, USA.
Head & Neck Oncology (Impact Factor: 3.14). 11/2010; 2:35. DOI: 10.1186/1758-3284-2-35
Source: PubMed

ABSTRACT The overall objective of this study was to develop a nanoparticle formulation for dual modality imaging of head and neck cancer. Here, we report the synthesis and characterization of polymeric phospholipid-based nanomicelles encapsulating near-infrared (NIR) phosphorescent molecules of Pt(II)-tetraphenyltetranaphthoporphyrin [Pt(TPNP)] and surface functionalized with gadolinium [Pt(TPNP)-Gd] for combined magnetic resonance imaging (MRI) and NIR optical imaging applications.
Dynamic light scattering, electron microscopy, optical spectroscopy and MR relaxometric measurements were performed to characterize the optical and magnetic properties of nanoparticles in vitro. Subsequently, in vivo imaging experiments were carried out using nude mice bearing primary patient tumor-derived human head and neck squamous cell carcinoma xenografts.
The nanomicelles were ~100 nm in size and stable in aqueous suspension. T1-weighted MRI and relaxation rate (R1 = 1/T1) measurements carried out at 4.7 T revealed enhancement in the tumor immediately post injection with nanomicelles, particularly in the tumor periphery which persisted up to 24 hours post administration. Maximum intensity projections (MIPs) generated from 3D T1-weighted images also demonstrated visible enhancement in contrast within the tumor, liver and blood vessels. NIR optical imaging performed (in vivo and ex vivo) following completion of MRI at the 24 h time point confirmed tumor localization of the nanoparticles. The large spectral separation between the Pt(TPNP) absorption (~700 nm) and phosphorescence emission (~900 nm) provided a dramatic decrease in the level of background, resulting in high contrast optical (NIR phosphorescence) imaging.
In conclusion, Pt(TPNP)-Gd nanomicelles exhibit a high degree of tumor-avidity and favorable imaging properties that allow for combined MR and optical imaging of head and neck tumors. Further investigation into the potential of Pt(TPNP)-Gd nanomicelles for combined imaging and therapy of cancer is currently underway.

Download full-text

Full-text

Available from: Tymish Y Ohulchanskyy, Jun 17, 2015
0 Followers
 · 
94 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is currently the eighth leading cause of cancer death worldwide. The often severe side effects, functional impairments and unfavorable cosmetic outcome of conventional therapies for HNSCC have prompted the quest for novel treatment strategies, including the evaluation of nanotechnology to improve e.g. drug delivery and cancer imaging. Although silica nanoparticles hold great promise for biomedical applications, they have not yet been investigated in the context of HNSCC. In the present in-vitro study we thus analyzed the cytotoxicity, uptake and intracellular fate of 200-300 nm core-shell silica nanoparticles encapsulating fluorescent dye tris(bipyridine)ruthenium(II) dichloride with hydroxyl-, aminopropyl- or PEGylated surface modifications (Ru@SiO2-OH, Ru@SiO2-NH2, Ru@SiO2-PEG) in the human HNSCC cell line UMB-SCC 745. We found that at concentrations of 0.125 mg/ml, none of the nanoparticles used had a statistically significant effect on proliferation rates of UMB-SCC 745. Confocal and transmission electron microscopy showed an intracellular appearance of Ru@SiO2-OH and Ru@SiO2-NH2 within 30 min. They were internalized both as single nanoparticles (presumably via clathrin-coated pits) or in clusters and always localized to cytoplasmic membrane-bounded vesicles. Immunocytochemical co-localization studies indicated that only a fraction of these nanoparticles were transferred to early endosomes, while the majority accumulated in large organelles. Ru@SiO2-OH and Ru@SiO2-NH2 nanoparticles had never been observed to traffic to the lysosomal compartment and were rather propagated at cell division. Intracellular persistence of Ru@SiO2-OH and Ru@SiO2-NH2 was thus traceable over 5 cell passages, but did not result in apparent changes in cell morphology and vitality. In contrast to Ru@SiO2-OH and Ru@SiO2-NH2 uptake of Ru@SiO2-PEG was minimal even after 24 h. Our study is the first to provide evidence that silica-based nanoparticles may serve as useful tools for the development of novel treatment options in HNSCC. Their long intracellular persistence could be of advantage for e.g. chronic therapeutic modalities. However, their complex endocytotic pathways require further investigations.
    Journal of Nanobiotechnology 08/2011; 9:32. DOI:10.1186/1477-3155-9-32
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction Iron-oxide nanoparticles can act as contrast agents in magnetic resonance imaging (MRI), while radiolabeling the same platform with nuclear medicine isotopes allows imaging with positron emission tomography (PET) or single-photon emission computed tomography (SPECT), modalities that offer better quantification. For successful translation of these multifunctional imaging platforms to clinical use, it is imperative to evaluate the degree to which the association between radioactive label and iron oxide core remains intact in vivo. Methods We prepared iron oxide nanoparticles stabilized by oleic acid and phospholipids which were further radiolabelled with 59Fe, 14C-oleic acid, and 111In. Results Mouse biodistributions showed 111In preferentially localized in reticuloendothelial organs, liver, spleen and bone. However, there were greater levels of 59Fe than 111In in liver and spleen, but lower levels of 14C. Conclusions While there is some degree of dissociation between the 111In labeled component of the nanoparticle and the iron oxide core, there is extensive dissociation of the oleic acid component.
    Nuclear Medicine and Biology 09/2014; DOI:10.1016/j.nucmedbio.2014.08.014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Theranostic magnetic resonance imaging (MRI) is now receiving a growing interest in imaging-guided drug delivery, monitoring the treatment and personalized administration etc. Theranostic agents are essential for the usage of theranostic MRI. Among different kinds of theranostic agents, gadolinium loaded nanoparticles (GdNPs) are one of the most promising theranostic agents which are very promising in combination of diagnostics (molecular imaging) and therapeutics (molecular therapy) functions in a single platform. In this review, we provided fully discussion on the design considerations of GdNPs as a platform for theranostic MRI. The mainly factors that affect the preparation process, such as GdNP materials, the loading of Gd/drugs in GdNPs, and the passive and active targeting strategies were discussed. Major classes of GdNPs including lipid-based nanoparticles, polymeric nanoparticles, micelles, dendrimers and Gd-silica nanoparticles were described in detail. The use of GdNPs as theranostic agents offers potential advantages that change the usual cancer therapy from separating diagnosis and treatment to theranostic approach.
    Biomaterials 04/2012; 33(21):5363-75. DOI:10.1016/j.biomaterials.2012.03.084