Porous nanoparticle supported lipid nanostructures

Abstract

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.

What is claimed is: 
     
         1 . A protocell nanostructure comprising:
 a porous particle core comprising a plurality of pores; and   at least one lipid bilayer surrounding the porous particle core to form a protocell, wherein the protocell is capable of loading one or more cargo components to the plurality of pores of the porous particle core and releasing the one or more cargo components from the porous particle core across the surrounding lipid bilayer.   
     
     
         2 . The nanostructure of  claim 1  further comprising a negatively charged porous particle core, a non-negatively charged lipid bilayer and a negatively charged cargo component. 
     
     
         3 . The nanostructure of  claim 1 , wherein each of the one or more cargo components comprises peptide, protein, antibody, DNA, RNA, fluorescent dye, inorganic nanoparticle cargo component, chemotherapeutic drug, or hydrophobic anti-cancer drug,
 wherein the inorganic nanoparticle cargo component comprises a gold nanoparticle, a magnetic nanoparticle or a quantum dot.   
     
     
         4 . The nanostructure of  claim 1 , wherein the porous particle core comprises a polymer hydrogel particle, or an inorganic particle. 
     
     
         5 . The nanostructure of  claim 1 , wherein the porous particle core is made of a material comprising polystyrene, silica, alumina, titania, or zirconia. 
     
     
         6 . The nanostructure of  claim 1 , wherein the porous particle core has a mean pore size ranging from about 2 nm to about 30 nm. 
     
     
         7 . The nanostructure of  claim 1 , wherein the porous particle core has a particle diameter ranging from about 30 nm to about 3000 nm. 
     
     
         8 . The nanostructure of  claim 1 , wherein the at least one lipid bilayer comprises a phospholipid comprising 1,2-Dioleoyl-3-Trimethylammonium-Propane (DOTAP), 1,2-Dioleoyl-sn-Glycero-3-Phosphocholine (DOPC) or a combination thereof. 
     
     
         9 . The nanostructure of  claim 1 , wherein the at least one lipid bilayer comprises a fluidic interface for a ligand display or for a multivalent targeting. 
     
     
         10 . A method for forming a loaded protocell comprising:
 providing a porous particle core, a lipid bilayer, and a cargo component; and   fusing the lipid bilayer to surround the porous particle core and synergistically loading the cargo component into one or more pores of the porous particle core to form a loaded protocell.   
     
     
         11 . The method of  claim 10  further comprising tuning a composition of the lipid bilayer to control the synergistic loading of the cargo component. 
     
     
         12 . The method of  claim 10  further comprising controlling one or more of an electrostatic charge, a surface wettability or a pore size of the porous particle core for the synergistic loading of the cargo component. 
     
     
         13 . The method of  claim 10  further comprising using excess amount of the lipid bilayer to improve colloidal stability of the loaded protocell. 
     
     
         14 . The method of  claim 10  further comprising forming the porous particle core by mixing water, HCl, ethanol, cetyltrimethylamonium bromide (CTAB), and tetraethyl orthosilicate (TEOS). 
     
     
         15 . The method of  claim 10  further comprising treating the porous particle core with ammonium hydroxide and hydrogen peroxide to provide a more hydrophilic surface. 
     
     
         16 . A method for delivering a cargo component using a protocell comprising:
 providing a porous particle core, a lipid bilayer, and one or more cargo components; wherein the lipid bilayer is fused onto the porous particle core and the one or more cargo components are synergistically loaded into one or more pores of the porous particle core to form a loaded protocell;   incubating a bioactive cell with the loaded protocell to internalize the loaded photocell within the bioactive cell; and   rupturing the lipid bilayer of the loaded photocell by applying a surfactant in preparation for transporting the one or more cargo components from the porous particle core into the bioactive cell.   
     
     
         17 . The method of  claim 16  further comprising:
 transporting the one or more cargo components into a targeted bioactive cell, wherein the lipid bilayer of the loaded protocell is modified with a targeting active species corresponding to the targeted bioactive cell. 
 
     
     
         18 . The method of  claim 16  further comprising releasing the cargo components from the porous particle core according to a pH value or an interaction of the porous particle core with the lipid bilayer. 
     
     
         19 . The method of  claim 16  further comprising releasing a doxocubicin cargo component into the bioactive cell through dissolution of a porous silica particle core. 
     
     
         20 . The method of  claim 16  further comprising releasing a calcein cargo component from the porous particle core by adjusting a pH value. 
     
     
         21 . The method of  claim 16  further comprising transporting a negatively charged DNA or a calcein dye into the bioactive cell. 
     
     
         22 . A delivery system according to the method of  claim 16 .