Abstract

In this study, we report the synthesis of gold-coated iron oxide nanoparticles capped with polyvinylpyrrolidone (Fe@Au NPs). The as-synthesized nanoparticles (NPs) exhibited good stability in aqueous media and excellent features as contrast agents (CA) for both magnetic resonance imaging (MRI) and X-ray computed tomography (CT). Additionally, due to the presence of the local surface plasmon resonances of gold, the NPs showed exploitable “light-to-heat” conversion ability in the near-infrared (NIR) region, a key attribute for effective photothermal therapies (PTT). In vitro experiments revealed biocompatibility as well as excellent efficiency in killing glioblastoma cells via PTT. The in vivo nontoxicity of the NPs was demonstrated using zebrafish embryos as an intermediate step between cells and rodent models. To warrant that an effective therapeutic dose was achieved inside the tumor, both intratumoral and intravenous routes were screened in rodent models by MRI and CT. The pharmacokinetics and biodistribution confirmed the multimodal imaging CA capabilities of the Fe@AuNPs and revealed constraints of the intravenous route for tumor targeting, dictating intratumoral administration for therapeutic applications. Finally, Fe@Au NPs were successfully used for an in vivo proof of concept of imaging-guided focused PTT against glioblastoma multiforme in a mouse model.

Highlights

  • Despite being the most frequent and aggressive primary malignant brain tumor in adults, few therapeutic advances have been achieved against glioblastoma multiforme (GBM)

  • Inspired by the above scenario, we report the application of surface-rough coreshell nanoparticles (Fe@Au NPs) as multimodal platforms for computed tomography (CT) and magnetic resonance imaging (MRI) imaging and photothermal therapy

  • The NPs suspension was placed into a 1 cm optical path quartz cuvette and irradiated for 5 min using a laser of 1064 nm (Laser Quantum, mpc6000/Ventus 1064) while recording the suspension temperature with a fiber optic sensor (TPT-62, FISO, Technologies Inc., Quebec, QC, Canada)

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Summary

Introduction

Despite being the most frequent and aggressive primary malignant brain tumor in adults, few therapeutic advances have been achieved against glioblastoma multiforme (GBM). On the other hand, combined therapies, that is, a therapeutic approach that combines multiple treatments to create synergistic or additive effects, are currently a hot topic in cancer therapy [50] Within this panorama, NPs based on iron oxide and gold NPs have attracted the attention of scientists because of their appealing features, such as capabilities as CAs for imaging and excellent SPR properties for biomedical applications [51,52,53]. Inspired by the above scenario, we report the application of surface-rough coreshell nanoparticles (Fe@Au NPs) as multimodal platforms for CT and MRI imaging and photothermal therapy The absorbance of these NPs in the near-infrared region allows the use of radiation inside the first biological window for conventional PTT. Imaging-guided PT therapy was evaluated in vivo

Materials
Physicochemical Characterization
Two-Photon Fluorescence Experiments
Photothermal Conversion
2.3.10. Photothermal Conversion Efficiency
2.3.11. Hyperthermia Calculations
Cell Culture
Cytotoxicity Assays
In Vitro Two-Photon Photodynamic Therapy
Teratogenicity Assay
In Vivo Pharmacokinetics and Biodistribution Experiments
In Vivo Magnetic Resonance Imaging
Tumor Implantation
Two-Photon In Vivo Photodynamic Therapy
Histology
Statistical Analysis
Physicochemical Characterization of the NPs
In Vitro Cytotoxicity Assessment in Cell Cultures
(Figures
Representative
Evaluation on on Zebrafish
Pharmacokinetics and Biodistribution Analysis
In Vivo Imaging-Guided TP-Photothermal Therapy
Methods
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