Abstract

Nanoparticle-based imaging contrast agents have drawn tremendous attention especially in multi-modality imaging. In this study, we developed mesoporous silica nanoparticles (MSNs) for use as dual-modality contrast agents for computed tomography (CT) and near-infrared (NIR) optical imaging (OI). A microwave synthesis for preparing naked platinum nanoparticles (nPtNPs) on MSNs (MSNs-Pt) was developed and characterized with physicochemical analysis and imaging systems. The high density of nPtNPs on the surface of the MSNs could greatly enhance the CT contrast. Inductively coupled plasma mass spectrometry (ICP-MS) revealed the MSNs-Pt compositions to be ~14% Pt by weight and TEM revealed an average particle diameter of ~50 nm and covered with ~3 nm diameter nPtNPs. To enhance the OI contrast, the NIR fluorescent dye Dy800 was conjugated to the MSNs-Pt nanochannels. The fluorescence spectra of MSNs-Pt-Dy800 were very similar to unconjugated Dy800. The CT imaging demonstrated that even modest degrees of Pt labeling could result in substantial X-ray attenuation. In vivo imaging of breast tumor-bearing mice treated with PEGylated MSNs-Pt-Dy800 (PEG-MSNs-Pt-Dy800) showed significantly improved contrasts in both fluorescence and CT imaging and the signal intensity within the tumor retained for 24 h post-injection.

Highlights

  • Nanoparticles (NPs)-based imaging contrast agents have emerged as a vigorous research area with agents such as iron oxide for magnetic resonance imaging (MRI) [1,2,3], quantum dots for optical imaging [4,5], and gold NPs for X-ray computed tomography (CT) [6,7,8] being developed

  • We developed a one-pot synthesis for preparing small-sized naked platinum nanoparticles on amine-modified mesoporous silica NPs via a microwave irradiation reduction process

  • Tetraethyl orthosilicate (TEOS), ammonium hydroxide (30%), and ethanol were purchased from Acros (Acros Organics, Geel, Belgium). (3-Aminopropyl)trimethoxysilane (APTMS), n-octane, and chloroplatinic acid hexahydrate (H2PtCl6) were obtained from Sigma Chemical Co

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Summary

Introduction

Nanoparticles (NPs)-based imaging contrast agents have emerged as a vigorous research area with agents such as iron oxide for magnetic resonance imaging (MRI) [1,2,3], quantum dots for optical imaging [4,5], and gold NPs for X-ray computed tomography (CT) [6,7,8] being developed. NPs can be modified with specific targeting molecules to enhance their delivery to tumors and, increase tumor contrast, a high percentage of administered NPs will accumulate in tissues/organs other than the targeted tumor. Substantial amounts of NPs residing in tissues/organs that do not undergo further biodegradation or excretion could cause unwanted cytotoxicity and other side effects [9,10,11,12,13,14,15]. Defining the characteristics of synthetic NPs that govern their biodegradation and/or excretion in vivo is a prerequisite for the successful application of such NPs as imaging contrast agents in clinical applications. We aimed to develop dual-modality NP-based contrast agents for tumor imaging. A single NP that possesses dual imaging modalities should provide a comprehensive diagnostic nanoplatform for cancer prognosis [18,19,20,21,22,23,24]

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