Controlled release nanoparticles and methods of use
Provided herein are nanoparticles that include a lipid layer and a compartment surrounded by the lipid layer. The lipid layer may include a lipid and a lipoprotein. The lipid may include a POPE lipid covalently attached to a hydrophilic polymer by a disulfide bond. The lipoprotein may include a trigger protein. The concentration of the first lipid may be between 1 mol % and 30 mol %. The disulfide bond of the first lipid is stable under conditions that include 10% human serum and is broken under conditions that include 50 micromolar glutathione. The hydrophilic polymer may include a PEG molecule. The trigger protein may include an amino acid repeat region, such as (GPX)n. The trigger protein may include a peptide bond that is cleaved by a gelatinase (e.g., gelatinase-B protease), or a member of the ADAM family of proteases (e.g., ADAM10 protease). Also provided are methods of using the nanoparticles.
1. A nanoparticle comprising a lipid layer and a compartment surrounded by the lipid layer,
wherein the lipid layer comprises (i) a first lipid, the first lipid comprising a POPE lipid covalently attached to a hydrophilic polymer by a disulfide bond, and (ii) a lipoprotein, the lipoprotein comprising a trigger protein,
wherein the concentration of the first lipid is between 1 mole percent (mol %) and 30 mol %, and
wherein the disulfide bond of the first lipid is stable under conditions comprising 10% human serum and is broken under conditions comprising 50 micromolar glutathione.
2. The nanoparticle of claim 1 wherein the trigger protein comprises an amino acid repeat region.
3. The nanoparticle of claim 2 wherein the amino acid repeat region comprises (GPX)n, wherein X is 4-hydroxyproline or proline, and n is at least 3.
4. The nanoparticle of claim 2 wherein the trigger protein comprises a peptide bond that is cleaved by a gelatinase or a member of the ADAM family of proteases.
5. The nanoparticle of claim 4 wherein the gelatinase is gelatinase-B protease.
6. The nanoparticle of claim 4 wherein the member of the ADAM family of proteases is ADAM10 protease.
7. The nanoparticle of claim 6 wherein the trigger protein comprises an amino acid sequence GPL GLA RKG (GPO) 4 (SEQ ID NO:15).
8. The nanoparticle of claim 1 wherein the compartment comprises a compound.
9. The nanoparticle of claim 8 wherein the compound is an inhibitor of a gelatinase or a member of the ADAM family of proteases.
10. The nanoparticle of claim 8 wherein the compound is a therapeutic agent.
11. The nanoparticle of claim 8 wherein the compound is a non-therapeutic agent.
12. A nanoparticle comprising a lipid layer and a compartment surrounded by the lipid layer,
wherein the lipid layer comprises (i) a first lipid, the first lipid covalently attached to a hydrophilic polymer by a disulfide bond, and (ii) a lipoprotein, the lipoprotein comprising a trigger protein, wherein the trigger protein comprises a peptide bond that is cleaved by a member of the ADAM family of proteases,
wherein the concentration of the first lipid is between 1 mole percent (mol %) and 30 mol %, and
wherein the disulfide bond of the first lipid is stable under conditions comprising 10% human serum and is broken under conditions comprising 50 micromolar glutathione.
13. The nanoparticle of claim 12 wherein the member of the ADAM family of proteases is ADAM10 protease.
14. The nanoparticle of claim 13 wherein the trigger protein comprises an amino acid sequence GPL GLA RKG (GPO) 4 (SEQ ID NO:15).
15. The nanoparticle of claim 12 wherein the compartment comprises a compound.
16. The nanoparticle of claim 15 wherein the compound is an inhibitor of a member of the ADAM family of proteases.
17. The nanoparticle of claim 15 wherein the compound is a therapeutic agent.
18. The nanoparticle of claim 15 wherein the compound is a non-therapeutic agent.
19. A method for delivering a compound to an environment, the method comprising:
providing the nanoparticle of claim 1 , wherein the compartment comprises a compound;
exposing the nanoparticle to an environment comprising (i) a reducing agent at a concentration sufficient to break the disulfide bond of the first lipid, and (ii) an enzyme that cleaves a peptide bond of the trigger protein, wherein exposure of the nanoparticle to the environment results in release of the compound from the compartment.