# US 8,771,642 B2 · Active particles for bio-analytical applications and methods for their preparation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,771,642 B2 - Document ID: US8771642B2 - Status: Granted - Kind: B2 - Application number: 13/056,752 - Filed: 2009-07-31 - Published: 2011-11-10 - Granted: 2014-07-08 - Earliest claimed: 2008-07-31 - Assignees: Alma Mater Studiorum - Università di Bologna - Applicants: Sara Bonacchi; Riccardo Juris; Marco Montalti; Luca Prodi; Enrico Rampazzo; Nelsi Zaccheroni - Inventors: Sara Bonacchi; Riccardo Juris; Marco Montalti; Luca Prodi; Enrico Rampazzo; Nelsi Zaccheroni - Web page: https://patentgrep.com/patent/US8771642B2 ## CPC - C07F 15/0053: {without a metal-carbon linkage} - A61K 49/0021: {the fluorescent group being a small organic molecule} - A61K 49/0032: {Methine dyes, e.g. cyanine dyes} - A61K 49/0041: {Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal (in vivo G01N)} - A61K 49/0043: {Fluorescein, used in vivo} - A61K 49/0093: {Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle} - C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract Nanoparticles, which are luminescent and/or electroactive and/or suitable for MRI (magnetic resonance imaging and/or PET (positron emission tomography) applications, comprise a micelle, which has a hydrophilic shell and an hydrophobic central portion, and a polysilicate core; the micelle comprises a plurality of molecules of a functionalized surfactant having the following structure: M1-Hydro1-Lipo-Hydro2-M2 wherein Lipo indicates a hydrophobic chain; Hydro1 ed Hydro2 indicate, each, a respective hydrophilic chain; M1 ed M2 represent respective recognition functionalities. ## Claims ### Claim 1 Particle comprising a micelle, which, on its turn, has a substantially hydrophilic shell and a substantially hydrophobic central portion; a core, which is located in the area of the micelle central portion and comprises a silicate network; and at least an active compound; the micelle comprising a plurality of molecules of at least a surfactant, which molecules comprise at least a molecule of a functionalized surfactant having the following structure: M1-Hydro1-Lipo-Hydro2-M2 wherein Lipo represent a substantially hydrophobic chain; Hydro1 and Hydro2 represent, independently of each other, a respective substantially hydrophilic chain; M1 has the following structure: RBM1-BL1- wherein RBM1 represents a recognition bio-molecule, BL1 represents a bridge linker chosen in the group consisting of: and amide; M2 is selected in the group consisting of: —H, —OH and the following structure: —BL2-RBM2 wherein RBM2 represents a recognition bio-molecule, BL2 represents a bridge linker chosen in the group consisting of: and amide; R20 being chosen in the group consisting of: —H, a linear alkyl group, a cyclo-alkyl group, an aromatic ring, a hetero-group; the surfactant and the active compound are different from each other; the molecules of the surfactant comprise a non functionalized surfactant having the following structure: Hydro3-Lipo1-Hydro4 wherein Lipo1 represent a substantially hydrophobic chain; Hydro3 and Hydro4 represent, independently of each other, a respective substantially hydrophilic chain; the molar ratio between the non functionalized surfactant and the functionalized surfactant is at least 3/1. ### Claim 2 (depends on 1) Particle according to claim 1, wherein BL1 represents a bridge linker chosen in the group consisting of: —NHCO— and —NHCOR19COO—; BL2 representing a bridge linker chosen in the group consisting of: —OR17CONH—, and —OCOR19CONH—; R17 and R19 being, independently of each other, a C1-C4 alkyl group; R20 being chosen in the group consisting of: —H, a C1-C4 alkyl group; the molar ratio between the non functionalized surfactant and the functionalized surfactant is up to 100/1. ### Claim 3 (depends on 1) Particle according to claim 1, wherein the recognition bio-molecule is chosen in the group consisting of: oligopeptide, polypeptide, oligonucleotide. ### Claim 4 (depends on 1) Particle according to claim 1, wherein M1 and M2 are identical to each other. ### Claim 5 (depends on 1) Particle according to claim 1, wherein the active compound is located in the area of the core; Lipo being substantially lipophilic; Hydro1 and Hydro2 being more soluble in water than in ethanol. ### Claim 6 (depends on 1) Particle according to claim 1, wherein the active compound is an emitting compound. ### Claim 7 (depends on 1) Particle according to claim 1, wherein the active compound is covalently bound to the silicate network. ### Claim 8 (depends on 1) Particle according to claim 1, and having an average hydrodynamic diameter in water lower than approximately 100 nm, in particular from approximately 40 nm to approximately 10 nm. ### Claim 9 (depends on 1) Particle according to claim 1, wherein the core has a diameter lower than approximately 30 nm, in particular from approximately 5 to approximately 15 nm. ### Claim 10 (depends on 1) Particle according to claim 1, wherein the micelle consists of a plurality of molecules of the functionalized surfactant. ### Claim 11 (depends on 1) Particle according to claim 1, wherein Hydro1 represents a chain wherein x is from 40 to 130 and R4 is a linear C1-C3 alkyl group; R16 is a C1-C4 alkyl group; Hydro2 represents a chain wherein z is from 40 to 130 and R5 is a linear C1-C3 alkyl group; Lipo represents a chain wherein y is from 20 to 85, R6 is a branched C3-C4 alkyl group; with the proviso that, where M1 is —COOH, M2 is —OR17COOH. ### Claim 12 (depends on 11) Particle according to claim 11, wherein Hydro1 represents a chain wherein x is from 80 to 120; R16 is a linear C1-C3 alkyl group: Hydro2 represents a chain wherein z is from 80 to 120; Lipo represents a chain wherein y is from 50 to 80. ### Claim 13 (depends on 11) Particle according to claim 11, wherein R16 is chosen in the group consisting of: —CH2— and —(CH2)2—. ### Claim 14 (depends on 1) Particle according to claim 1, wherein the functionalized surfactant has an average molecular weight of at least 6 KDa; the ratios between the Lipo average molecular weight and the Hydro1 average molecular weight and between the Lipo average molecular weight and the Hydro2 average molecular weight being, independently of each other, from approximately 0.4 to approximately 2.0. ### Claim 15 (depends on 1) Particle according to claim 1, wherein said molecules of surfactant comprise a non-functionalized surfactant; the ratio between the non-functionalized and functionalized surfactants is lower than 200/1, in particular from 100/1 to 1/100. ### Claim 16 (depends on 1) A particle according to claim 1, obtainable by a method comprising a reaction step during which a plurality of molecules of at least an alkoxysilane are silanazed in the presence of at least an active compound, water and a plurality of molecules of at least a functionalized surfactant; the alkoxysilane being chosen between a tetraalkoxysilane and a trialkoxysilane; the functionalized surfactant being as defined in claim 1 wherein, during the reaction step, the molecules of alkoxysilane are silanazed together with the active compound; wherein, during the reaction step, the molecules of alkoxysilane are silanazed together with the active compound.