Porous nanoparticle supported lipid bilayer nanostructures
View Patent ↗Various exemplary embodiments provide protocell nanostructures and methods for constructing and using the protocell nanostructures. In one embodiment, the protocell nanostructures can include a core-shell structure including a porous particle core surrounded by a shell of lipid bilayer(s). The protocell can be internalized in a bioactive cell. Various cargo components, for example, drugs, can be loaded in and released from the porous particle core of the protocell(s) and then delivered within the bioactive cell.
1. A protocell nanostructure comprising:
a negatively charged porous silica particle core comprising a plurality of pores;
a non-negatively charged fused lipid bilayer on the surface of said porous particle core; and
a negatively charged cargo component which is loaded into said pores of said porous particle core by combining said cargo with non-negatively charged lipid when said lipid forms said lipid bilayer, wherein said particle core has a particle diameter ranging from about 30 nm to about 3000 nm and is capable of releasing said cargo from the porous particle core at a pH below 7.
2. The protocell nanostructure of claim 1 , wherein said cargo is a negatively charged chemotherapeutic drug or nucleic acid.
3. The protocell nanostructure of claim 2 , wherein said porous particle core comprises a polymer hydrogel particle or an inorganic particle.
4. The protocell nanostructure of claim 1 , wherein the lipid bilayer comprises a phospholipid selected from the group consisting of 1,2-Dioleoyl-3-Trimethylammonium-Propane (DOTAP), 1,2-Dioleoyl-sn-Glycero-3-Phosphocholine (DOPC) or a combination thereof.
5. The protocell nanostructure of claim 2 , wherein said lipid bilayer comprises 1,2-Dioleoyl-3-Trimethylammonium-Propane (DOTAP).
6. The protocell nanostructure of claim 2 , wherein said lipid bilayer comprises 1,2-Dioleoyl-sn-Glycero-3-Phosphocholine (DOPC).
7. The protocell nanostructure of claim 2 , wherein said lipid bilayer comprises a mixture of 1,2-Dioleoyl-3-Trimethylammonium-Propane (DOTAP) and 1,2-Dioleoyl-sn-Glycero-3-Phosphocholine (DOPC).
8. A delivery system for delivering a cargo component from a protocell nanostructure, said delivery system comprising a population of protocell nanostructures, each nanostructure comprising a negatively charged porous silica particle core comprising a plurality of pores, a non-negatively charged fused lipid bilayer on the surface of said porous particle core; and one or more negatively charged cargo components which are loaded into said pores of said porous particle core by combining said cargo with non-negatively charged lipid when said lipid forms said bilayer, wherein said particle core has a particle diameter ranging from about 30 nm to about 3000 nm and is capable of releasing said cargo from said porous particle core at a pH below 7.
9. The delivery system according to claims 8 , wherein said cargo is a negatively charged chemotherapeutic drug or nucleic acid.
10. The delivery system according to claim 8 , wherein said porous particle core comprises a polymer hydrogel particle or an inorganic particle.
11. The delivery system according to claim 8 , wherein the lipid bilayer comprises a phospholipid selected from the group consisting of 1,2-Dioleoyl-3-Trimethylammonium-Propane (DOTAP), 1,2-Dioleoyl-sn-Glycero-3-Phosphocholine (DOPC) or a combination thereof.
12. The delivery system according to claim 9 , wherein said lipid bilayer comprises 1,2-Dioleoyl-3-Trimethylammonium-Propane (DOTAP).
13. The delivery system according to claim 9 , wherein said lipid bilayer comprises 1,2-Dioleoyl-sn-Glycero-3-Phosphocholine (DOPC).
14. The delivery system according to claim 9 , wherein said lipid bilayer comprises a mixture of 1,2-Dioleoyl-3-Trimethylammonium-Propane (DOTAP) and 1,2-Dioleoyl-sn-Glycero-3-Phosphocholine (DOPC).