Mechanical opening of lipid bilayers by molecular nanomachines

Patent metadata

Field	Value
Publication number	US-11565003-B2
Application number	US-202117233102-A
Country	US
Kind code	B2
Filing date	Apr 16, 2021
Priority date	Jul 14, 2016
Publication date	Jan 31, 2023
Grant date	Jan 31, 2023

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.

First claim

What is claimed is:

1. A method of causing cell death by opening a lipid bilayer of the cell, wherein the method comprises:
embedding the lipid bilayer with a molecular motor comprising at least a base component of the molecular motor, wherein the molecular motor comprises the base component capable of embedding with the lipid bilayer comprising three annulated rings or three annulated aromatic rings;
and a moving component capable of moving in response to an energy source and of the formula:

wherein the lipid bilayer is a component of a cell membrane, and exposing the lipid bilayer to an energy source,

wherein the exposing occurs after the embedding,
wherein the exposing causes the moving component of the embedded molecular motor to rotate,
wherein the rotation of the moving component facilitates the opening of the lipid bilayer; and the rotation is sufficient to lead to cell death.

2. The method of claim 1 , wherein the energy source comprises a wavelength of 355 nm or higher wavelength.

3. The method of claim 1 , wherein the energy source is selected from the group consisting of ultraviolet light, visible light, near-infra red light, a radio frequency energy source, a magnetic field, a two-photon energy source, an electric field, an electromagnetic field, and combinations thereof.

4. The method of claim 1 , wherein the moving component is capable of rotating after exposure to an energy source comprising a wavelength of 355 nm or higher wavelength.

5. The method of claim 1 , wherein the embedding occurs in vitro.

6. The method of claim 1 , wherein the embedding occurs in vivo in a subject.

7. The method of claim 6 , wherein the embedding comprises administering the molecular motor to the subject.

8. The method of claim 7 , wherein the molecular motor is co-administered with the energy source.

9. The method of claim 7 , wherein the molecular motor is co-administered with an active agent.

10. The method of claim 1 , wherein the molecular motor further comprises a targeting agent for directing the molecular motor to a desired lipid bilayer, a tracing agent for tracking the molecular motor, a solubilizing agent for maintaining the water solubility of the molecular motor, an active agent releasably associated with the molecular motor, or combinations thereof.

11. The method of claim 1 , wherein the molecular motor is capable of simultaneously interacting with the lipid bilayer and the external stimulus energy source.

12. The method of claim 1 , further comprising embedding wherein the moving component embeds with the lipid bilayer.

13. The method of claim 1 , wherein the molecular motor comprises 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, 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, and
wherein R 3 comprises the moving component.

14. The method of claim 4 , wherein the moving component is capable of rotating after exposure to an energy source comprising a wavelength of 400 nm or higher wavelength.

15. The method of claim 13 , wherein at least one of R 1 , R 2 or R 3 comprises an electron donating group.

16. The method of claim 1 , wherein the lipid bilayer is a component of a nuclear membrane, and wherein the opening of the nuclear membrane allows for the passage of materials through the nuclear membrane.

17. The method of claim 1 , wherein the lipid bilayer is a component of a cell membrane, a nuclear membrane, an organelle membrane, or any combination thereof.

18. The method of claim 1 , wherein the base component or the moving component further comprise one or more groups selected from: alkanes, alkenes, alkynes, carboxyl groups, ketone groups, alkoxy groups, ethers, nitro groups, nitriles, sulfates, sulfonates, halogens, amine groups, amide groups, alcohols, aromatic groups, annulated rings, and combinations thereof.

Assignees

• Univ Rice William M
• Univ Durham

Inventors

• Tour James M
• Pal Robert
• García López Victor
• Nilewski Lizanne

Classifications

• A61K49/0032 Primary

  Methine dyes, e.g. cyanine dyes · CPC title

• C09B57/00

  Other synthetic dyes of known constitution · CPC title

• A61K49/0021

  the fluorescent group being a small organic molecule · CPC title

• C09B23/04

  one >CH- group, e.g. cyanines, isocyanines, pseudocyanines · CPC title

• A61K41/00

  Medicinal preparations obtained by treating materials with wave energy or particle radiation {; Therapies using these preparations} · CPC title