Abstract
BackgroundThe 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.MethodsDynamic 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.ResultsThe 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.ConclusionsIn 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.
Highlights
The overall objective of this study was to develop a nanoparticle formulation for dual modality imaging of head and neck cancer
Synthesis of Pt(TPNP)/Gd nanomicelles We have recently described the procedure for synthesis of nanomicelles encapsulating the phosphorescent dye, Pt(II)-tetraphenyltetranaphthoporphyrin [Pt(TPNP)] in the hydrophobic core of the DSPE-polyethylene glycol (PEG)/DSPC nanomicelles [7]
Zeta potential studies carried out with the Pt(TPNP)-Gd nanomicelles have shown an overall negative zeta potential owing to the presence of the PEG molecules on the surface of the nanomicelles
Summary
The overall objective of this study was to develop a nanoparticle formulation for dual modality imaging of head and neck cancer. Diagnostic evaluation of head and neck tumors often involves the use of non-invasive imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). Development of agents that allow imaging of tumors across multiple platforms could be potentially beneficial for diagnostic and therapeutic evaluation of cancer in patients. In this regard, nanoparticle-based platforms have several distinct advantages that could potentially allow integration of diagnostic and therapeutic applications in oncology [3,4,5]. Nanoparticles can be used as carriers to selectively deliver high doses of multiple therapeutic agents to cancer sites while minimizing delivery to normal tissues [4,5]
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