Functionalized silica nanorings, methods of making same, and uses thereof

Patent metadata

Field	Value
Publication number	US-2025019249-A1
Application number	US-202418616147-A
Country	US
Kind code	A1
Filing date	Mar 25, 2024
Priority date	Apr 15, 2019
Publication date	Jan 16, 2025
Grant date	—

Abstract

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.

First claim

1 . A silica nanoring 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.

2 . The silica nanoring of claim 1 , having an outer diameter of 5 nm to 20 nm.

3 . The silica nanoring of claim 1 , wherein the single aperture of the silica nanoring has an inside diameter of 3 nm to 13 nm.

4 . 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.

5 . 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.

6 . 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 comprising a one or more fluorescent group(s) covalently bound to the silica matrix.

7 . (canceled)

8 . A composition comprising a plurality of silica nanorings of claim 1 .

9 . (canceled)

10 . The composition of claim 8 , the composition further comprising one or more pharmaceutical carrier(s).

11 . A method of making silica nanorings comprising
forming a reaction mixture comprising
one or more silica precursor(s);
one or more surfactant(s);
one or more pore expander(s); and
holding the reaction mixture at a time and temperature, whereby the silica nanorings are formed; and adding a PEG-silane, PEG-silane conjugate comprising a display group, or a combination thereof to the reaction mixture.

12 . The method of claim 11 , 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.

13 . The method of claim 11 , wherein the one or more surfactant(s) is/are present in the reaction mixture at a concentration of 1 mg/mL to 50 mg/mL and/or the one or more pore expander(s) is/are present at a concentration of 0.05 mg/mL to 150 mg/mL.

14 . The method of claim 11 , wherein the molar ratio of the one or more surfactant(s) to the one or more pore expander(s) is 1:2 to 1:10.

15 . (canceled)

16 . The method of claim 11 , 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).

17 .- 19 . (canceled)

20 . The method of claim 11 , 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 resulting reaction mixture at a second time and second temperature, and subsequently heating the resulting reaction mixture at a third time and third temperature, whereby silica nanorings surface functionalized with PEG groups comprising a display group are formed.

21 . (canceled)

22 . The method of claim 11 , wherein the reaction mixture further comprises water and the pH of the reaction mixture is 6-9.

23 . (canceled)

24 . A method of determining the location of one or more display group(s) on a silica nanoring of claim 1 comprising subjecting the silica nanoring to high performance liquid chromatography (HPLC) analysis.

25 .- 31 . (canceled)

32 . The method of claim 25 , further comprising utilizing gel permeation chromatography (GPC) and/or utilizing fluorescence correlation spectroscopy (FCS) to determine the number of display groups and/or silica nanorings.

33 . (canceled)

34 . A method for purifying a plurality of silica nanorings of claim 1 comprising subjecting the plurality of silica nanorings to liquid chromatography and selecting a portion of the plurality of silica nanorings; and optionally, identifying the selected portion of the plurality of silica nanorings.

35 .- 41 . (canceled)

42 . A method for imaging of a region within an individual comprising:
administering to the individual a plurality of silica nanorings of claim 1 , wherein the silica nanorings comprise one or more dye group(s), one or more radioisotope group(s), one or more iodide(s), or the like; or a combination thereof; directing excitation electromagnetic radiation into the subject, thereby exciting at least one of the one or more dye molecule(s), one or more radioisotope(s), or one or more iodide(s); detecting excited electromagnetic radiation, the detected electromagnetic radiation having been emitted by the one or more dye molecule(s), one or more radioisotope(s), one or more iodide(s) in the individuals as a result of excitation by the excitation electromagnetic radiation; and processing signals corresponding to the detected electromagnetic radiation to provide one or more image(s) of the region within the individual.

43 . (canceled)

44 . A method of treating cancer in an individual comprising administering to the subject a therapeutically effective amount of a composition comprising one or more silica nanoring(s) of claim 1 , wherein the individual's cancer is treated.

45 .- 50 . (canceled)

Assignees

• Univ Cornell

Inventors

• Turker Melik Z
• Gardinier Ii Thomas C
• Wiesner Ulrich B
• Ma Kai

Classifications

• A61K9/51

  Nanocapsules; {Nanoparticles; (nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00)} · CPC title

• A61K33/00 Primary

  Medicinal preparations containing inorganic active ingredients · CPC title

• A61K49/005

  characterised by the carrier molecule carrying the fluorescent agent · CPC title

• A61K51/1244

  microparticles or nanoparticles, e.g. polymeric nanoparticles · CPC title

• A61K49/0093

  Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle · CPC title