ROS—responsive liposomes for specific targeting
Provided herein are encapsulated liposomes comprising a lipid bilayer, a first polyethylene glycol (PEG) corona, a targeting molecule and a second PEG corona. The second, encapsulating PEG corona can be reversibly linked to the first PEG corona. Also provided are pharmaceutical compositions comprising the encapsulated liposomes and methods of treating a subject with a disease characterized by production of reactive oxygen species (ROS) with the compositions. Also provided are methods of making the encapsulated liposomes disclosed herein.
1. An encapsulated liposome comprising
(a) a lipid bilayer with a first polyethylene glycol (PEG) corona, wherein the first PEG corona further comprises a targeting molecule, and
(b) a second PEG corona reversibly linked to the first PEG corona, wherein the reversible links comprise a boronic ester bond.
2. The liposome of claim 1 , wherein the reversible links are oxidized and then hydrolyzed in the presence of reactive oxygen species and water.
3. The liposome of claim 1 , wherein at least a portion of the second PEG corona is released in the presence of reactive oxygen species and water.
4. The liposome of claim 3 , wherein release of the second PEG corona exposes the targeting molecule.
5. The liposome of claim 1 , wherein the targeting molecule is selected from the group consisting of a nucleic acid, polypeptide, lipid, carbohydrate, small molecule, and any combination thereof.
6. The liposome of claim 1 , wherein the lipid bilayer comprises lipids selected from the group consisting of phospholipids, sphingolipids, glycosphingolipids, saturated glycerides, steroids, synthetic phospholipids, and any combination thereof.
7. The liposome of claim 1 , wherein the liposome further comprises one or more active agents.
8. The liposome of claim 7 , wherein the one or more active agents are contained within the liposome, attached to the lipid bilayer, or any combination thereof.
9. The liposome of claim 7 , wherein the one or more active agents are released in the presence of reactive oxygen species.
10. The liposome of claim 7 , wherein the active agent is selected from the group consisting of a nucleic acid, polypeptide, antibody, small molecule, and any combination thereof.
11. A pharmaceutical composition comprising the liposome of claim 1 and a pharmaceutically acceptable carrier.
12. The liposome of claim 1 , wherein the boronic ester bond is formed from a linker selected from the group consisting of an aryl boronic acid, a phenylboronate, a pyridylboronate, and a cyclohexylboronate.
13. The liposome of claim 1 , wherein the boronic ester bond is formed from a linker selected from the group consisting of 4-bromomethylphenyl boronic acid pinacol ester, 3-(N,N-dimethylamino)phenyl boronic acid, 2,4-dichlorophenylboronic acid, 4-aminocarbonylphenylboronic acid, 3-chlorophenylboronic acid, 4-hydroxyphenylboronic acid, 4-propylphenylboronic acid, 3-[(E)-2-nitrovinyl)phenylboronic acid, 4-chlorocarbonylphenylboronic anhydride, cyclopenten-1-ylboronic acid, 2-bromopyridine-3-boronic acid, 2,4-ditert-butoxypyrimidin-5-ylboronic acid, 2,4-bis(benzyloxy)pyrimidine-5-boronic acid, 5-phenyl-2-thienylboronic acid, and 5-formylthiophene-3-boronic acid.