Small Multifunctional Nanoclusters (Nanoroses) for Targeted Cellular Imaging and Therapy

Abstract

The ability of 20-50 nm nanoparticles to target and modulate the biology of specific types of cells will enable major advancements in cellular imaging and therapy in cancer and atherosclerosis. A key challenge is to load an extremely high degree of targeting, imaging, and therapeutic functionality into small, yet stable particles. Herein we report ~30 nm stable uniformly sized near-infrared (NIR) active, superparamagnetic nanoclusters formed by kinetically controlled self-assembly of goldcoated iron oxide nanoparticles. The controlled assembly of nanocomposite particles into clusters with small primary particle spacings produces collective responses of the electrons that shift the absorbance into the NIR region. The nanoclusters of ~70 iron oxide primary particles with thin gold coatings display intense NIR (700-850 nm) absorbance with a cross section of ~10 −14 m 2 . Because of the thin gold shells with an average thickness of only 2 nm, the r 2 spin-spin magnetic relaxivity is 219 mM −1 s −1 , an order of magnitude larger than observed for typical iron oxide particles with thicker gold shells. Despite only 12% by weight polymeric stabilizer, the particle size and NIR absorbance change very little in deionized water over 8 months. High uptake of the nanoclusters by macrophages is facilitated by the dextran coating, producing intense NIR contrast in dark field and hyperspectral microscopy, both in cell culture and an in vivo rabbit model of atherosclerosis. Small nanoclusters with optical, magnetic, and therapeutic functionality, designed by assembly of *Address correspondence to: kpj@che.utexas.edu, FELDMANM@uthscsa.edu. Supporting Information Available: Reproducibility in nanorose size distribution; porosity of dextran in the shells about the iron oxide particle; estimation of number of particles per nanocluster; average optical density spectra in macrophages labeled with nanorose by hyperspectral microscopy; and laser vaporization of macrophages in vitro. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public AccessAuthor Manuscript ACS Nano. Author manuscript; available in PMC 2010 September 22. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript nanoparticle building blocks, offer broad opportunities for targeted cellular imaging, therapy, and combined imaging and therapy. Keywordsgold; iron oxide; nanocluster; near-infrared; macrophage targeted imaging; MRI; atherosclerosis; cancer Clinical imaging and/or therapy with multifunctional nanoparticles that target specific types of cells has the potential to transform health care in cancer, atherosclerosis, and other diseases. When the nanoparticle diameters are reduced to 20-50 nm, the biological pathways in targeted cells can undergo profound changes. [1][2][3][4][5] Small nanoparticles, the size of small viruses, permeate barriers more rapidly including cell membranes and leaky vasculature in cancers. The efficacy of vaccines may be enhanced with ultrasmall 20 nm nanoparticles that can dif...

Room-temperature synthesis of gold nanoparticles — Size-control by slow addition

“…The TEM image of the sample prepared at an MR value of 5.2 has several branched flower-like particles that are similar to the 'nanoroses' described in a recent report (26). The mean size (diameter of an equivalent circle having the same projected area) is not reported due to the highly irregular shape of the particles.…”

Colloidal magnetic nanocrystal clusters: variable length-scale interaction mechanisms, synergetic functionalities and technological advantages

“…In this direction, improved or collective physical properties can be obtained by bringing magnetic nanocrystals next to one another at distances where they can interact. If preformed, they can be encapsulated in an organic [13][14][15][16][17] or inorganic [18][19][20] matrix in order to form an aggregate or can grow and assemble together at high temperature via a single-step process. Colloidal assemblies of either type have been stabilized by the balance between the electrostatic, entailing the capping molecules and the magnetic interactions involving the incorporated inorganic subunits.…”

Assessing the hyperthermic properties of magnetic heterostructures: the case of gold–iron oxide composites

“…The gold-iron oxide composites exhibit the occurrence of the 15 nm-sized iron oxide USM nanoparticles accompanied by submicrometre flower-like structures. Branched and flower-like morphology has been widely reported both for nanostructured gold, and for gold-iron oxide nanoheterostructures [27,30,39].…”