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(12) Patent Application Publication (10) Pub. No.: US 2014/0248210 A1 Bradbury Et Al US 2014024821 OA1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0248210 A1 Bradbury et al. (43) Pub. Date: Sep. 4, 2014 (54) MULTIMODAL SILICA-BASED (52) U.S. Cl. NANOPARTICLES CPC ......... A61K 51/1244 (2013.01); A61K 49/0093 (71) Applicants: CORNELL UNIVERSITY, Ithaca, NY (2013.01); A61K 47/48884 (2013.01) (US); SLOAN-KETTERING USPC .............. 424/1.29: 424/9.6; 424/9.4: 42479.3 INSTITUTE FOR CANCER RESEARCH, New York, NY (US) (57) ABSTRACT (72) Inventors: Michelle Bradbury, New York, NY The present invention provides a fluorescent silica-based (US); Ulrich Wiesner, Ithaca, NY (US); nanoparticle that allows for precise detection, characteriza Oula Penate Medina, Kiel (DE); tion, monitoring and treatment of a disease such as cancer. ity t N."NSS): The nanoparticle has a range of diameters including between SS, in on N.Y. S.Rs. about 0.1 nm and about 100 nm, between about 0.5 nm and Tom Quinn, Columbia, MO (US) s about 50 nm, between about 1 nm and about 25 nm, between about 1 nm and about 15 nm, or between about 1 nm and about (73) Assignees: CORNELL UNIVERSITY, Ithaca, NY 8 nm. The nanoparticle has a fluorescent compound posi RSSSSS tioned within the nanoparticle, and has greater brightness and RESEARCH, New York, NY (US) fluorescent quantum yield than the free fluorescent com pound. The nanoparticle also exhibits high biostability and (21) Appl. No.: 14/215,879 biocompatibility. To facilitate efficient urinary excretion of the nanoparticle, it may be coated with an organic polymer, (22)22) FileFiled: Mara 17, 2014 such as poly(ethylene glycol) (PEG). The small size of the Related U.S. Application Data nanoparticle, the silica base and the organic polymer coating (63) Continuation-in-part of application No. 13/381,209 minimizes the toxicity of the nanoparticle when administered filed on Sep. 27 PS 2 R aS application No. PCT, in vivo. In order to target a specific cell type, the nanoparticle US 10/4O994 on Jul. 2,200. may further be conjugated to a ligand, which is capable of (60) Provisional application No. 61/794,414, filed on Mar. binding to a cellular component associated with the specific 15, 2013, provisional application No. 61/222,851, cell type, such as a tumor marker. In one embodiment, a filed on Jul. 2, 2009, provisional application No. therapeutic agent may be attached to the nanoparticle. To 61/312,827, filed on Mar. 11, 2010. permit the nanoparticle to be detectable by not only optical O O fluorescence imaging, but also other imaging techniques, Publication Classification Such as positron emission tomography (PET), single photon (51) Int. Cl emission computed tomography (SPECT), computerized A6 IK5I/2 (2006.01) tomography (CT), bioluminescence imaging, and magnetic A6 IK 47/48 (2006.01) resonance imaging (MRI), radionuclides/radiometals or A6 IK 49/00 (2006.01) paramagnetic ions may be conjugated to the nanoparticle. Patent Application Publication Sep. 4, 2014 Sheet 1 of 50 US 2014/024821.0 A1 e Patent Application Publication Sep. 4, 2014 Sheet 2 of 50 US 2014/024821.0 A1 R. i. Patent Application Publication Sep. 4, 2014 Sheet 3 of 50 US 2014/024821.0 A1 Emission (x10') As 64 & c. A 3 s {{ {{x : s c.c. : c si. W is & N. 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