Functionalized silica nanorings, methods of making same, and uses thereof
Silica nanorings, methods of making silica nanorings, and uses of silica nanorings. The silica nanorings may be PEGylated. The silica nanorings may be surface functionalized, which may be surface selective functionalization, with one or more polyethylene glycol (PEG) group(s), one or more display group(s), one or more functional group(s), or a combination thereof. The silica nanorings may have a size of 5 to 20 nm. The silica nanorings may be made using micelles. The absence or presence of the micelles during PEGylation and/or functionalization allows for surface selective functionalization. The silica nanorings may be used in various diagnostic and/or treatment methods.
1 . A silica nanoring comprising a silica matrix, defining a single aperture and comprising an outer surface and an inner surface, wherein at least a portion of or substantially all of the outer surface, and optionally, at least a portion of or substantially all of the inner surface, or all of the surfaces of the silica nanoring are functionalized with polyethylene glycol (PEG) groups, functionalized PEG groups, or a combination thereof, and at least a portion of or all the silica matrix of the silica nanoring is microporous,
wherein the silica nanoring has an outer diameter or 5 nm to 20 nm and/or the single aperture of the silica nanoring has an inside diameter of 3 nm to 13 nm.
2 . The silica nanoring of claim 1 , wherein the at least a portion or substantially all or all of the outer surface and/or at least a portion or substantially all or all of the inner surface is functionalized with one or more display group(s) chosen from peptide groups, nucleic acid groups, antibody groups, antibody fragment groups, dye groups, metal chelating groups, radiolabel groups, radiotherapeutics, drug groups, drug-linker groups, sensor groups, functional groups, and combinations thereof.
3 . A composition comprising a plurality of silica nanorings of claim 1 .
4 . The composition of claim 3 , the composition further comprising one or more pharmaceutical carrier(s).
5 . A method of making silica nanorings of claim 1 comprising:
forming a reaction mixture comprising:
one or more silica precursor(s);
one or more surfactant(s); and
one or more pore expander(s);
holding the reaction mixture at a time and temperature, whereby the silica nanorings are formed; and
adding a PEG-silane, a PEG-silane conjugate comprising a display group, or a combination thereof to the reaction mixture,
wherein the silica nanorings of claim 1 are formed.
6 . The method of claim 5 , further comprising functionalization of at least a portion of an outer surface and/or at least a portion of an inner surface of the silica nanorings with one or more display group(s).
7 . The method of claim 5 , wherein the silica nanorings of claim 1 comprise an interior, the method further comprising removing substantially all or all of the one or more surfactant(s) and/or the one or more pore expander(s) from the interior of the silica nanorings.
8 . The method of claim 5 , wherein before or after the PEG-silane is added, adding a PEG-silane conjugate comprising a display group is added at room temperature to the reaction mixture,
holding the reaction mixture at a second time and second temperature, and
subsequently heating the reaction mixture at a third time and third temperature, whereby silica nanorings surface functionalized with PEG groups comprising a display group are formed.
9 . The method of claim 5 , wherein at least a portion of or all of the PEG-silane has a reactive group on a terminus of the PEG group opposite the terminus conjugated to a silane group of the PEG-silane conjugate and after formation of the silica nanoring surface functionalized with PEG groups having a reactive group, and, optionally, PEG groups, are reacted with a second display group functionalized with a second reactive group thereby forming silica nanorings surface functionalized with PEG groups functionalized with a second display group and, optionally, PEG groups.
10 . The method of claim 5 , wherein the reaction mixture further comprises water and a pH, and the pH of the reaction mixture is 6-9.
11 . A silica nanoring comprising a silica matrix, a hydrodynamic size of 7 nm to 15 nm, a single pore comprising a diameter of 4 nm to 8 nm, and an outer surface and an inner surface, wherein at least a portion of or substantially all of the outer surface, and optionally, at least a portion of or substantially all of the inner surface, or all of the surfaces of the silica nanoring are functionalized with polyethylene glycol (PEG) groups.
12 . The silica nanoring of claim 11 , wherein the at least a portion of or all of the outer surface is functionalized with PEG groups, independently at each occurrence comprising 6, 7, 8, or 9 ethyleneoxide groups, and, optionally, one or more drug group(s), and at least a portion of or all of the inner surface is functionalized with PEG groups, independently at each occurrence comprising 2, 3, or 4 ethylene oxide groups, and, optionally, one or more drug groups(s), and the silica matrix of the nanoring comprises one or more fluorescent group(s) covalently bound to the silica matrix.
13 . The silica nanoring of claim 11 , wherein the at least a portion or substantially all or all of the outer surface and/or at least a portion or substantially all or all of the inner surface is functionalized with one or more display group(s) chosen from peptide groups, nucleic acid groups, antibody groups, antibody fragment groups, dye groups, metal chelating groups, radiolabel groups, radiotherapeutics, drug groups, drug-linker groups, sensor groups, functional groups, and combinations thereof.
14 . The silica nanoring of claim 11 , wherein the silica nanoring is a diagnostic agent, drug delivery agent, a therapeutic agent, a theranostic agent, or a combination thereof.
15 . The silica nanoring of claim 1 , wherein the single aperture comprises a diameter of 4 nm to 8 nm.
16 . The silica nanoring of claim 1 , wherein the silica nanoring comprises more than one display group and at least a portion of the display groups are structurally distinct.
17 . The silica nanoring of claim 1 , wherein the at least a portion of or all of the outer surface is functionalized with PEG groups, independently at each occurrence comprising 6, 7, 8, or 9 ethyleneoxide groups, and, optionally, one or more drug group(s), and at least a portion of or all of the inner surface is functionalized with PEG groups, independently at each occurrence comprising 2, 3, or 4 ethylene oxide groups, and, optionally, one or more drug groups(s), and the silica matrix of the nanoring comprises one or more fluorescent group(s) covalently bound to the silica matrix.
18 . The silica nanoring of claim 1 , wherein the silica nanoring is a diagnostic agent, drug delivery agent, a therapeutic agent, a theranostic agent, or a combination thereof.
19 . The method of claim 5 , wherein
the one or more surfactant(s) is/are chosen from C 10 to C 18 alkyltrimethylammonium halides, sodium dodecyl sulfate (SDS), N-myristoyl-L-glutamic acid (C14GluA), and combinations thereof, and/or
the one or more pore expander(s) is/are chosen from trialkylated benzene, polymer monomers, hydrophobic solvents, cycloalkanes, benzene, alkylated benzene, chlorinated alkanes, and combinations thereof.
20 . The method of claim 5 , wherein the one or more silica precursor(s) is/are chosen from tetraalkoxysilanes, alkyltrialkoxysilanes, functionalized silica precursors, and combinations thereof.
21 . The method of claim 5 , wherein reaction mixture comprises a molar ratio of moles of the one or more surfactant(s) to moles of the one or more pore expander(s) and the molar ratio is 1:2 to 1:10.
22 . The method of claim 5 , wherein at least a portion of or all of the one or more of the silica precursor(s) comprises one or more display group(s).
23 . A silica nanoring comprising a silica matrix, defining a single aperture and comprising an outer surface and an inner surface, wherein at least a portion of or substantially all of the outer surface, and optionally, at least a portion of or substantially all of the inner surface, or all of the surfaces of the silica nanoring are functionalized with polyethylene glycol (PEG) groups, functionalized PEG groups, or a combination thereof, and at least a portion of or all the silica matrix of the silica nanoring is microporous,
wherein the at least a portion of or all of the outer surface is functionalized with PEG groups, independently at each occurrence, comprising 6, 7, 8, or 9 ethylene oxide groups, and, optionally, one or more drug group(s), and at least a portion of or all of the inner surface is functionalized with PEG groups, independently at each occurrence comprising 2, 3, or 4 ethylene oxide groups, and, optionally, one or more drug groups(s), and the silica matrix of the nanoring comprises one or more fluorescent group(s) covalently bound to the silica matrix.