Protocells and their use for targeted delivery of multicomponent cargos to cancer cells
View Patent ↗Various embodiments provide materials and methods for synthesizing protocells for use in targeted delivery of cargo components to cancer cells. In one embodiment, the lipid bilayer can be fused to the porous particle core to form a protocell. The lipid bilayer can be modified with targeting ligands or other ligands to achieve targeted delivery of cargo components that are loaded within the protocell to a target cell, e.g., a type of cancer. Shielding materials can be conjugated to the surface of the lipid bilayer to reduce undesired non-specific binding.
1. A protocell comprising:
a porous silica nanoparticle core comprising a plurality of pores, said nanoparticle core being formed from an aqueous precursor mixture comprising tetraethylorthosilicate (TEOS) and an amine-modified silane precursor, said porous silica nanoparticle core having an average particle size ranging from about 30 nm to about 3000 nm; and
a supported lipid bilayer encasing the porous particle core and supported by the porous particle core,
wherein said lipid bilayer consists essentially of a zwitterionic phosphoholipid selected from the group consisting of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), dipalmitoylphosphatidylcholine (DPPC) and a mixture thereof, and wherein said protocell, after administration to a subject, decreases non-specific binding of said protocells in said subject when compared to protocells which are encased with a lipid bilayer comprising positively or negatively charged phospholipids.
2. The protocell according to claim 1 wherein said amine-modified silane precursor is selected from the group consisting of 3-2[2-(2-aminoethylamino)ethylamino]propyltrimethoxysilane (AEPTMS), 3-aminopropyltrimethoxysilane (APTMS)nanostructure and a mixture thereof and said amine-modified silane precursor comprises about 5% to about 30% by weight of said precursor mixture.
3. The protocell according to claim 1 wherein the lipid bilayer is fused to the porous particle core and has a melting transition temperature T m which is less than that of a corresponding lipid bilayer which is unsupported or supported without fusion.
4. The protocell according to claim 1 wherein said zwitterionic phospholipid is DOPC or a mixture of DOPC and DPPC.
5. The protocell according to claim 1 wherein said zwitterionic phospholipid is DOPC.
6. The protocell according to claim 1 wherein the plurality of pores has an average pore size ranging from about 2 nm to about 30 nm.
7. The protocell according to claim 4 wherein the plurality of pores has an isotropic wormlike nanoporosity.
8. The protocell according to claim 1 , wherein said lipid bilayer has a thickness ranging from about 1 nm to about 5 nm.
9. The protocell according to claim 1 further comprising one or more cargo components is disposed within the porous particle core and a targeting ligand attached to the lipid bilayer for increasing selective binding of said protocell to a target cell; and an optional shielding material attached to the lipid bilayer for reducing non-specific binding to the target cell and non-target cells.
10. The protocell according to claim 1 wherein a fusogenic peptide is attached to the lipid bilayer, the fusogenic peptide comprising a histidine-rich fusogenic peptide H5WYG having a sequence of SEQ ID NO:1.
11. The protocell according to claim 9 wherein a fusogenic peptide is attached to the lipid bilayer, the fusogenic peptide comprising a histidine-rich fusogenic peptide H5WYG having a sequence of SEQ ID NO:1.
12. The protocell according to claim 9 wherein said one or more cargo components are selected from the group consisting of protein toxins, plasmid DNAs, siRNAs, nanoparticles, diphtheria toxins, doxorubicins, 5-fluorouracils, cisplatins and mixtures thereof.
13. The protocell according to claim 9 wherein said shielding material is selected from the group consisting of polyethylene glycol, cholesterol and mixtures thereof.
14. The protocell according to claim 9 wherein said one or more cargo components is DNA or RNA.
15. The protocell according to claim 14 wherein said cargo component is DNA.
16. The protocell according to claim 14 wherein said cargo component is RNA.
17. The protocell according to claim 1 wherein said amine-modified silane precursor is selected from the group consisting of 3[2-(2-aminoethylamino)ethylamino]propyltrimethoxysilane (AEPTMS), 3-aminopropyltriethoxysilane (APTES) and a mixture thereof and said amine-modified silane precursor comprises about 5% to about 30% by weight of said precursor mixture.