Dual Imaging Gold Nanoplatforms for Targeted Radiotheranostics.

Francisco Silva,António Paulo,Amália S Jurado,M Margarida C.A Castro,Carlos F.G.C Geraldes,Pilar López-Larrubia,Ana M Cardoso,Éva Tóth,Sara Lacerda,Fernanda Marques,Agnès Pallier,Sandra Même,Maria Paula Cabral Campello,Lurdes Gano

doi:10.3390/ma13030513

Abstract

Gold nanoparticles (AuNPs) are interesting for the design of new cancer theranostic tools, mainly due to their biocompatibility, easy molecular vectorization, and good biological half-life. Herein, we report a gold nanoparticle platform as a bimodal imaging probe, capable of coordinating Gd3+ for Magnetic Resonance Imaging (MRI) and 67Ga3+ for Single Photon Emission Computed Tomography (SPECT) imaging. Our AuNPs carry a bombesin analogue with affinity towards the gastrin releasing peptide receptor (GRPr), overexpressed in a variety of human cancer cells, namely PC3 prostate cancer cells. The potential of these multimodal imaging nanoconstructs was thoroughly investigated by the assessment of their magnetic properties, in vitro cellular uptake, biodistribution, and radiosensitisation assays. The relaxometric properties predict a potential T1- and T2- MRI application. The promising in vitro cellular uptake of 67Ga/Gd-based bombesin containing particles was confirmed through biodistribution studies in tumor bearing mice, indicating their integrity and ability to target the GRPr. Radiosensitization studies revealed the therapeutic potential of the nanoparticles. Moreover, the DOTA chelating unit moiety versatility gives a high theranostic potential through the coordination of other therapeutically interesting radiometals. Altogether, our nanoparticles are interesting nanomaterial for theranostic application and as bimodal T1- and T2- MRI / SPECT imaging probes.

Highlights

The primary source of information for clinical diagnostic applications comes from medical imaging.The available molecular imaging modalities provide different information about the patient with different spatial and temporal resolution and sensitivity
Their Au and Gd3+ contents were determined by ICP-OES and it was found that the maximum content of gadolinium that could be incorporated into the nanoplatform corresponds to the ratio Au:Gd3+ 1:0.25 (Table 1)
In vitro studies evidence a good internalization in PC3 tumor cells of the particles when functionalized with a bombesin derivative

Summary

Introduction

The primary source of information for clinical diagnostic applications comes from medical imaging.The available molecular imaging modalities provide different information about the patient with different spatial and temporal resolution and sensitivity. AuNPs are versatile nanoplatforms that can be functionalized with several imaging agents, plus biological targeting moieties and drugs, combining therapeutic and diagnostic functions within a single nanoparticle [4,5,6,7,8] While this concept is auspicious, AuNPs have to overcome multiple hurdles to reach their full potential in clinical applications. The real “magic gold nanoparticle” still remains an unmet goal despite the recent and encouraging results that have been reported for target-specific AuNPs applied to cancer theranostics This progress is only at the proof-of-concept stage and its application to clinical trials is still a few years away [9,10,11]

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Discussion

Conclusion