Modified ultrasmall nanoparticles as multimodal imaging agents for biomedical applications

Objectives
The synthesis of multimodal imaging agents is a growing research field and a lot of work is currently being done in this area because of its wide biomedical applications. The idea behind the use of nuclear and optical dual labelled imaging probes is the possibility to synergistically exploit the advantages of positron emission tomography (PET) and optical imaging. The dual labelled imaging agents combat the limitations of sensitivity, spatial and temporal resolution and also tissue penetrability [1]. The combination of the two imaging modalities may provide complementary information for improving diagnosis, allows image guided surgery as well as fluorescence microscopy of tissue biopsies.

Methods
Ultrasmall silicon nanoparticles (SiNPs) of size <5 nm are potential candidates in this perspective due to their hydrophilicity, biocompatibility, luminescence properties and the possibility to covalently functionalize their surface [2,3]. Amine-terminated ultrasmall silicon nanoparticles were prepared according to a reported method with slight modifications [4]. Here we report the functionalization of amine-terminated SiNPs with the sulfo-cyanine 5 dye (sCy5) to obtain an optical imaging probe and with biomolecules, such as single-domain antibodies (sdAb) for active targeting of a cancer biomarker. SiNPs are also modified with radiolabel such as 64Cu, coordinated to bispidines [5], to obtain a dual, nuclear and optical, probe.
Results
The renal clearance property of these biocompatible, hydrophilic ultrasmall SiNPs are the major highlights of this research. The modified particles tend to eliminate from the body within very small period of time, rendering them as excellent tools for biomedical purposes.

Conclusions
The functionalization of SiNPs with fluorescent dyes, radiotracers and targeting moieties will open the path for targeted dual imaging of cancer, possibly allowing diagnosis and therapy in in vivo systems.

References
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[3] C.-H. Lai, J. Hütter, C.-W. Hsu, H. Tanaka, S. Varela-Aramburu, L. De Cola, B. Lepenies, and P. H. Seeberger, Nano Lett. 2016, 16, 807−811.
[4] Y. Zhong, F. Peng, F. Bao, S. Wang, X. Ji, L. Yang, Y. Su, S.-T. Lee, Y. He, J. Am. Chem. Soc. 2013, 135, 8350- 8356.
[5] H. Stephan, M. Walther, S. Fähnemann, P. Ceroni, J. Molloy, G. Bergamini, F. Heisig, C. E. Müller, W. Kraus, and P. Comba, Chem. Eur. J., 2014, 20, 17011-17018.