Near-Infrared Imaging Method for the In Vivo Assessment of the Biodistribution of Nanoporous Silicon Particles

In the development of new nanoparticle-based technologies for therapeutic and diagnostic purposes, understanding the fate of nanoparticles in the body is crucial. We recently developed a multistage vector delivery system comprising biodegradable and biocompatible nanoporous silicon particles (first-stage microparticles [S1MPs]) able to host, protect, and deliver second-stage therapeutic and diagnostic nanoparticles (S2NPs) on intravenous injection. This delivery system aims at sequentially overcoming the biologic barriers en route to the target delivery site by separating and assigning tasks to the coordinated logic-embedded vectors constituting it. In this work, by conjugating a near-infrared dye on the surface of the S1MP without compromising the porous structure and potential loading of S2NPs, we were able to monitor the in vivo distribution of S1MPs in healthy mice using an optical imaging system. It was observed that particles predominantly accumulated in the liver and spleen at the end of 24 hours. Further quantification of S1MPs in the major organs of the animals by elemental analysis of silicon using inductively coupled plasma-atomic electron spectroscopy verified the accuracy of in vivo near-infrared imaging as a tool for evaluation of nanovector biodistribution.

[1]  Mauro Ferrari,et al.  Geometrical confinement of gadolinium-based contrast agents in nanoporous particles enhances T1 contrast , 2010, Nature nanotechnology.

[2]  J. Salonen,et al.  Mesoporous silicon in drug delivery applications. , 2008, Journal of pharmaceutical sciences.

[3]  Intraoperative Imaging of Pancreas Transplant Allografts Using Indocyanine Green with Laser Fluorescence , 2008, Proceedings.

[4]  M. Ferrari,et al.  Intracellular trafficking of silicon particles and logic-embedded vectors. , 2010, Nanoscale.

[5]  Mauro Ferrari,et al.  Nanomedicine—Challenge and Perspectives , 2009 .

[6]  Samir Mitragotri,et al.  Role of target geometry in phagocytosis. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[7]  J. Chao,et al.  Biofunctionalisation of porous silicon (PS) surfaces by using homobifunctional cross-linkers , 2006 .

[8]  Michael J Sailor,et al.  Biomolecular screening with encoded porous-silicon photonic crystals , 2002, Nature Materials.

[9]  Mauro Ferrari,et al.  Mitotic trafficking of silicon microparticles. , 2009, Nanoscale.

[10]  Mauro Ferrari,et al.  Sustained small interfering RNA delivery by mesoporous silicon particles. , 2010, Cancer research.

[11]  L. Canham,et al.  Transition Metal Complex-Doped Hydroxyapatite Layers on Porous Silicon , 1998 .

[12]  Mauro Ferrari,et al.  Tailored porous silicon microparticles: fabrication and properties. , 2010, Chemphyschem : a European journal of chemical physics and physical chemistry.

[13]  A. Loni,et al.  In-Vivo Assessment of Tissue Compatibility and Calcification of Bulk and Porous Silicon , 1998 .

[14]  L. Canham Bioactive silicon structure fabrication through nanoetching techniques , 1995 .

[15]  W. Freeman,et al.  Porous silicon in drug delivery devices and materials. , 2008, Advanced drug delivery reviews.

[16]  M. Ferrari,et al.  Quantitative mechanics of endothelial phagocytosis of silicon microparticles , 2009, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[17]  Aya Nakagawa,et al.  Intraoperative identification of sentinel lymph nodes by near-infrared fluorescence imaging in patients with breast cancer. , 2008, American journal of surgery.

[18]  Wei Wang,et al.  Near infrared fluorescent optical imaging for nodal staging. , 2008, Journal of biomedical optics.

[19]  Arjun G. Yodh,et al.  Non-invasive assessment of tumor neovasculature: techniques and clinical applications , 2008, Cancer and Metastasis Reviews.

[20]  M. Turina,et al.  Novadaq SPY: intraoperative quality assessment in off-pump coronary artery bypass grafting. , 2004, Chest.

[21]  A. Cerami Inflammatory cytokines. , 1992, Clinical immunology and immunopathology.

[22]  Mauro Ferrari,et al.  Tailoring the degradation kinetics of mesoporous silicon structures through PEGylation. , 2010, Journal of biomedical materials research. Part A.

[23]  Mauro Ferrari,et al.  Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications. , 2008, Nature nanotechnology.

[24]  Mauro Ferrari,et al.  Cellular association and assembly of a multistage delivery system. , 2010, Small.

[25]  R. Weissleder A clearer vision for in vivo imaging , 2001, Nature Biotechnology.

[26]  Jennifer S. Park,et al.  Oxidation-triggered release of fluorescent molecules or drugs from mesoporous Si microparticles. , 2008, ACS nano.

[27]  Vesa-Pekka Lehto,et al.  Biocompatibility of thermally hydrocarbonized porous silicon nanoparticles and their biodistribution in rats. , 2010, ACS nano.

[28]  L. Canham Silicon quantum wire array fabrication by electrochemical and chemical dissolution of wafers , 1990 .

[29]  W. Freeman,et al.  Intravitreal properties of porous silicon photonic crystals: a potential self-reporting intraocular drug-delivery vehicle , 2008, British Journal of Ophthalmology.

[30]  S. Bhatia,et al.  Probing the Cytotoxicity Of Semiconductor Quantum Dots. , 2004, Nano letters.

[31]  J. West,et al.  Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy. , 2007, Nano letters.

[32]  D. Kiel,et al.  Dietary silicon intake and absorption. , 2002, The American journal of clinical nutrition.

[33]  R. Moats,et al.  In vivo Near-Infrared Fluorescence Imaging of Integrin αvβ3 in Brain Tumor Xenografts , 2004, Cancer Research.

[34]  David J. Wallis,et al.  Dissolution of different forms of partially porous silicon wafers under simulated physiological conditions , 2003 .

[35]  V. Lehto,et al.  Mesoporous silicon microparticles for oral drug delivery: loading and release of five model drugs. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[36]  S. Gambhir,et al.  Quantum Dots for Live Cells, in Vivo Imaging, and Diagnostics , 2005, Science.

[37]  John V Frangioni,et al.  Image-guided sentinel lymph node mapping and nanotechnology-based nodal treatment in lung cancer using invisible near-infrared fluorescent light. , 2009, Seminars in thoracic and cardiovascular surgery.

[38]  E M Carlisle,et al.  Silicon: A Possible Factor in Bone Calcification , 1970, Science.

[39]  Michael J Sailor,et al.  Biodegradable luminescent porous silicon nanoparticles for in vivo applications. , 2009, Nature materials.

[40]  W Kenneth Ward,et al.  A review of the foreign-body response to subcutaneously-implanted devices: the role of macrophages and cytokines in biofouling and fibrosis. , 2008, Journal of diabetes science and technology.

[41]  K. Barla,et al.  Pore Size Distribution in Porous Silicon Studied by Adsorption Isotherms , 1983 .

[42]  R. Langer,et al.  Relating the phagocytosis of microparticles by alveolar macrophages to surface chemistry: the effect of 1,2-dipalmitoylphosphatidylcholine. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[43]  S. Ossicini,et al.  Porous silicon: a quantum sponge structure for silicon based optoelectronics , 2000 .

[44]  A. Boskey,et al.  Molecular imaging promotes progress in orthopedic research. , 2006, Bone.

[45]  M Ferrari,et al.  Size and shape effects in the biodistribution of intravascularly injected particles. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[46]  C. Prestidge,et al.  Loading and release of a model protein from porous silicon powders , 2007 .

[47]  Nicolas H Voelcker,et al.  The biocompatibility of porous silicon in tissues of the eye. , 2009, Biomaterials.

[48]  K. Avgoustakis,et al.  Biodistribution properties of nanoparticles based on mixtures of PLGA with PLGA-PEG diblock copolymers. , 2005, International journal of pharmaceutics.

[49]  Martin Wolf,et al.  Progress of near-infrared spectroscopy and topography for brain and muscle clinical applications. , 2007, Journal of biomedical optics.

[50]  Mauro Ferrari,et al.  Antibiological barrier nanovector technology for cancer applications , 2007, Expert opinion on drug delivery.