Mechanical opening of lipid bilayers by molecular nanomachines

Abstract

Embodiments of the present disclosure pertain to methods of opening a lipid bilayer by associating the lipid bilayer with a molecule that includes a moving component capable of moving (e.g., rotating) in response to an external stimulus; and exposing the molecule to an external stimulus before, during or after associating the molecule with the lipid bilayer. The exposing causes the moving component of the molecule to move and thereby open the lipid bilayer (e.g., by pore formation). The external stimuli may include an energy source, such as ultraviolet light. The opened lipid bilayer may be a component of cell membranes in vitro or in vivo. The opening of the lipid bilayer may allow for the passage of various materials (e.g., active agents, such as peptide-based drugs) through the lipid bilayer and into cells. Additional embodiments of the present disclosure pertain to the aforementioned molecules for opening lipid bilayers.

1 . A molecule having the following structure: 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are each independently selected from the group consisting of hydrogen, alkanes, alkenes, alkynes, carboxyl groups, ketone groups, alkoxy groups, methoxy groups, ethers, nitro groups, nitriles, sulfates, sulfonates, halogens, amine groups, amide groups, alcohols, aromatic groups, aryl groups, phenyl groups, annulated rings, carbohydrates, polysaccharides, peptides, targeting agents, tracing agents, fluorophores, solubilizing agents, active agents, and combinations thereof; 
         wherein X is selected from the group consisting of S, CH 2 , and O, 
         wherein R 3  has one of the following structures: 
       
       
         
           
           
               
               
           
         
       
     
     
         2 . The molecule of  claim 1 , having the following structure: 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are each independently selected from the group consisting of hydrogen, alkanes, alkenes, alkynes, carboxyl groups, ketone groups, alkoxy groups, methoxy groups, ethers, nitro groups, nitriles, sulfates, sulfonates, halogens, amine groups, amide groups, alcohols, aromatic groups, aryl groups, phenyl groups, annulated rings, carbohydrates, polysaccharides, peptides, targeting agents, tracing agents, fluorophores, solubilizing agents, active agents, and combinations thereof. 
       
     
     
         3 . The molecule of  claim 1 , wherein R 1  and R 2  are each independently selected from the group consisting of hydrogen, alkanes, alkenes, alkynes, nitro groups, nitriles, amine groups, amide groups, annulated rings, carbohydrates, polysaccharides, peptides, targeting agents, tracing agents, fluorophores, solubilizing agents, active agents, and combinations thereof, and X is S. 
     
     
         4 . The molecule of  claim 3 , wherein R 1  and R 2  are each independently selected from the group consisting of hydrogen, alkanes, alkenes, alkynes, nitro groups, nitriles, amine groups, amide groups and combinations thereof. 
     
     
         5 . The molecule of  claim 1 , having the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The molecule of  claim 5 , selected from the group consisting of: 
       
         
           
           
               
               
           
         
         or combinations thereof. 
       
     
     
         7 . The molecule of  claim 1 , comprising a targeting agent for directing the molecule to a desired lipid bilayer, optimally wherein the targeting agent is selected from the group consisting of amino acids, peptides, proteins, aptamers, antibodies, small molecules, carbohydrates, polysaccharides, and combinations thereof. 
     
     
         8 . The molecule of  claim 1  comprising a tracing agent for tracking the molecule, optionally wherein the tracing agent is selected from the group consisting of fluorophores, chromophores, dyes, radio-labeled molecules, radioactive nuclei, high contrast agents, gadolinium, gallium, thallium, fluorinated compounds, and combinations thereof. 
     
     
         9 . The molecule of  claim 1  comprising a solubilizing agent for maintaining the water solubility of the molecule, optionally wherein the solubilizing agent is selected from the group consisting of peptides, glycols, alcohols, carboxylates, polysaccharides, salts, acids, polyethers, polyethylene glycols (PEGs), carbohydrates, and combinations thereof. 
     
     
         10 . The molecule of  claim 1  comprising an active agent, optionally wherein the active agent is releasably associated with the molecule, and/or optionally wherein the active agent is selected from the group consisting of drugs, peptides, polypeptides, nucleotides, DNA, RNA, siRNA, enzymes, and combinations thereof.