Silica nanoparticle composition for delivering bioactive material or protein such as a human proteasome
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Publication Number
US-11786469-B2
Publication Date
2023-10-17
Expiration Date
Abstract
A composition for delivering a bioactive material include a porous silica nanoparticle containing pores with an average pore diameter ranging from 1 nm to 100 nm, at least one of (i) a functional group which binds to the pore surface of the porous silica nanoparticle and gives the pore surface a negative charge or a positive charge, (ii) a ligand which binds to the pore surface of the porous silica nanoparticle and specifically binds to the bioactive material, and (iii) a combination of the functional group and the ligand, and a bioactive material having a size to be accommodated within the pores of the porous silica nanoparticle, the bioactive material bound to said at least one of the functional group and the ligand bound to the pore surface of the mesoporous silica nanoparticle and accommodated within the pores of the porous silica nanoparticle.
Core Innovation
The disclosed invention provides an expanded porous silica nanoparticle drug-delivery platform for delivering bioactive materials, including proteins and other bioactive materials accommodated within expanded pores. The nanoparticle has an expanded pore structure with a pore surface and an outer surface, and the pore surface is functionalized to provide at least one of a functional group that gives the pore surface a negative charge or a positive charge and/or a ligand that specifically binds to the bioactive material.
The disclosure includes binding and loading via ligand options such as nickel, nickel-nitrilotriacetic acid, glutathione, dextrin, and biotin or streptavidin, together with charge-conferring functional groups. It emphasizes protection of proteins from degradation and improved intracellular delivery, including delivery of the 26S human proteasome using nickel-NTA/His-tag interactions.
It further describes optional targeting moieties and surface PEGylation to reduce aggregation and non-specific binding, and reports that preserved proteasome activity can lead to reduced tau aggregation and improved resistance to proteotoxic/ROS stress in cell models.
Claims Coverage
The document provides two independent claims. Across the independent claims, the core inventive features involve producing expanded porous silica nanoparticles with expanded pore sizes in a stated range, binding a bioactive material within the expanded pores via pore-surface functional groups and/or specified ligands, and requiring the protein to be a 26S human proteasome.
Expanded porous silica nanoparticle with expanded pore structure
An expanded porous silica nanoparticle having an expanded pore structure, with a pore surface forming the pores and an outer surface.
Preparation by silica precursor with surfactant and expanding agent followed by heating and surfactant removal
The expanded porous silica nanoparticle is produced by stirring a mixture of a silica precursor having a pore diameter of less than 5 nm with a surfactant, treating the silica nanoparticle with an expanding agent to prepare a mixture, heating the mixture, and removing the surfactant to obtain the expanded porous silica nanoparticle with a pore diameter of 10 nm to 100 nm.
Pore-surface functional group or ligand for binding to the bioactive material
At least one of a functional group which binds to the pore surface and gives the pore surface a negative charge or a positive charge, a ligand which binds to the pore surface and specifically binds to the bioactive material, or a combination of the functional group and the ligand, wherein the ligand includes nickel, nickel-nitrilotriacetic acid, glutathione, dextrin, biotin or streptavidin.
Bioactive protein accommodated within pores and bound to pore surface chemistry; 26S human proteasome
A bioactive material having a size to be accommodated within the pores of the expanded porous silica nanoparticle, where the bioactive material bound to the functional group and/or ligand is accommodated within the pores, wherein the bioactive material is a protein having a size from 14.7 kDa to 2,000 kDa, and wherein the protein is a 26S human proteasome.
TMOS/defined surfactant mesoporous formation, sonicating, heating, and expanding agent treatment to produce expanded pores
The expanded porous silica nanoparticle is produced by forming a mesoporous silica nanoparticle with a pore diameter of less than 5 nm by mixing tetramethoxy silane with a surfactant selected from CTAB, TMABr, TMPrCl, and TMACl, sonicating a solution containing the mesoporous silica nanoparticle, treating it with an expanding agent selected from trimethylbenzene and N,N-dimethylhexadecylamine, heating the mixture, and removing the surfactant to obtain the expanded porous silica nanoparticle with a pore diameter of 10 nm to 100 nm.
Across the independent claims, the inventive concept is delivering a bioactive protein, specifically a 26S human proteasome, using an expanded porous silica nanoparticle with pore-surface functional groups and/or specified ligands to bind and accommodate the protein within pores of 10 nm to 100 nm.
Stated Advantages
Protection of proteins from degradation.
Improved intracellular delivery.
Preserved proteasome activity.
Reduced tau aggregation.
Improved resistance to proteotoxic/ROS stress in cell models.
Documented Applications
Delivery of the 26S human proteasome via nickel-NTA/His-tag interactions for intracellular applications.
Delivery of other proteins including RNase and IgG, including in vivo tumor-size and fluorescence-retention experiments for other proteins.
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