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Biodegradable luminescent porous silicon nanoparticles for in vivo applications

Abstract

Nanomaterials that can circulate in the body hold great potential to diagnose and treat disease1,2,3,4. For such applications, it is important that the nanomaterials be harmlessly eliminated from the body in a reasonable period of time after they carry out their diagnostic or therapeutic function. Despite efforts to improve their targeting efficiency, significant quantities of systemically administered nanomaterials are cleared by the mononuclear phagocytic system before finding their targets, increasing the likelihood of unintended acute or chronic toxicity. However, there has been little effort to engineer the self-destruction of errant nanoparticles into non-toxic, systemically eliminated products. Here, we present luminescent porous silicon nanoparticles (LPSiNPs) that can carry a drug payload and of which the intrinsic near-infrared photoluminescence enables monitoring of both accumulation and degradation in vivo. Furthermore, in contrast to most optically active nanomaterials (carbon nanotubes, gold nanoparticles and quantum dots), LPSiNPs self-destruct in a mouse model into renally cleared components in a relatively short period of time with no evidence of toxicity. As a preliminary in vivo application, we demonstrate tumour imaging using dextran-coated LPSiNPs (D-LPSiNPs). These results demonstrate a new type of multifunctional nanostructure with a low-toxicity degradation pathway for in vivo applications.

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Figure 1: Characterization of LPSiNPs.
Figure 2: Biocompatibility and biodegradability of LPSiNPs.
Figure 3: In vitro, in vivo and ex vivo fluorescence imaging with LPSiNPs.
Figure 4: Fluorescence images of tumours containing D-LPSiNPs.

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Acknowledgements

This work was supported by the National Cancer Institute of the National Institutes of Health through grant numbers U54 CA 119335 (UCSD CCNE), 5-R01-CA124427 (BRP) and U54 CA119349 (MIT CCNE). M.J.S., S.N.B. and E.R. are members of the Moores UCSD Cancer Center and the UCSD NanoTUMOR Center under which this work was conducted and supported by the NIH/NCI grant. J.-H.P. thanks the Korea Science and Engineering Foundation (KOSEF) for a Graduate Study Abroad Scholarship. The authors thank Melanie L. Oakes in the Hitachi Chemical Research for assistance with SEM analysis, Edward Monosov in the Burnham Institute for Medical Research for assistance with confocal and multi-photon microscopy and Nissi Varki of the Moores UCSD Cancer Center for toxicity examination of the histology samples.

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J.-H.P., L.G. and M.J.S. conceived and designed the research. J.-H.P. and L.G. carried out the experiments. J.-H.P., L.G., G.v.M., E.R., S.N.B. and M.J.S. analysed the data. J.-H.P. and M.J.S. wrote the manuscript.

Corresponding author

Correspondence to Michael J. Sailor.

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Park, JH., Gu, L., von Maltzahn, G. et al. Biodegradable luminescent porous silicon nanoparticles for in vivo applications. Nature Mater 8, 331–336 (2009). https://doi.org/10.1038/nmat2398

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