IP Library › Granted Patent US 12,195,620
Granted Patent B2
US 12,195,620 · App. 18/253,766 · Granted Jan 14, 2025

Controlled entrapment and release of molecular cargo

Inventors: Faik Akif Tezcan (La Jolla, CA); Ling Zhang (La Jolla, CA); Youjeong Na (La Jolla, CA); Kenneth Han (San Diego, CA)
Assignee: The Regents of the University of California
C08L51/10A61K9/4833A61K38/47C08F292/00C12Y302/01017C08F2438/03
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Quick Facts
Patent No.
US 12,195,620
App. No.
18/253,766
Granted
Jan 14, 2025
Kind
B2
Abstract

Disclosed are reversibly-expandable polymer-integrated crystals (PIX) materials, devices, and methods for controllably encapsulating and releasing molecular cargo. The disclosed PIX materials are engineered crystalline materials with large pores that can entrap macromolecules, such as proteins and nanoparticles. The material expands and contracts reversibly, allowing controlled encapsulation and release of guest/cargo molecules.

Claims (50)

1. A reversibly-expandable polymer-integrated crystal (PIX) material for controllably entrapping and releasing a molecular cargo, comprising:

a crystal comprising ferritin molecules organized in a crystal lattice, wherein the ferritin molecules are conjugated with a reversible addition-fragmentation chain-transfer (RAFT) agent; and

a polymer matrix comprising polyacrylate formed within the crystal lattice of the crystal such that the polymer matrix encompasses the ferritin molecules,

wherein the polymer matrix is configured to cause the crystal lattice to expand in response to a first stimulus and configured to cause the crystal lattice to contract, when the crystal lattice is expanded, in response to a second stimulus which is different from the first stimulus,

wherein the PIX material is operable to capture the molecular cargo by loading molecules of the molecular cargo within the crystal lattice of the PIX material when the crystal lattice is expanded and is operable to entrap the molecules of the molecular cargo within the PIX material by contracting the crystal lattice with the loaded molecules of the molecular cargo contained within the crystal lattice, and

wherein the PIX material is operable to release the molecules of the molecular cargo, comprising re-expanding the crystal lattice after entrapment of the molecules of the molecular cargo within the PIX material.

2. The PIX material of claim 1 , wherein said loading the molecules of the molecular cargo within the crystal lattice of the PIX material when the crystal lattice is expanded comprises allowing the molecules of the molecular cargo to permeate the polymer matrix of the PIX material from an environment outside the PIX material.

3. The PIX material of claim 1 , wherein the polymer matrix includes a hydrogel.

4. The PIX material of claim 3 , wherein the hydrogel is a polyacrylate hydrogel.

5. The PIX material of claim 1 , wherein the RAFT agent is a maleimide-functionalized trithiocarbonate RAFT agent.

6. The PIX material of claim 1 , wherein the RAFT agent is a cysteine-specific RAFT agent.

7. The PIX material of claim 6 , wherein each molecule from the ferritin molecules includes a single set of surface-exposed cysteine residues at positions 157 flanking the ferritin C 4 symmetry axes.

8. The PIX material of claim 1 , wherein the crystal is an isotropic crystal.

9. The PIX material of claim 8 , wherein the crystal has a cubic symmetry.

10. The PIX material of claim 1 , wherein the crystal is an anisotropic crystal.

11. The PIX material of claim 10 , wherein the crystal has a rhombohedral or a trigonal symmetry.

12. The PIX material of claim 10 , wherein the PIX material is operable to expand anisotropically in response to the first stimulus.

13. The PIX material of claim 1 , wherein the PIX material is operable to reversibly expand in response to the first stimulus by more than 100% in volume.

14. The PIX material of claim 1 , wherein the molecular cargo includes a protein, a DNA, an RNA, or a nanoparticle.

15. The PIX material of claim 1 , wherein the first stimulus includes one or more of: (i) a change in ionic strength of an environment comprising the PIX material; (ii) a change in a pH of the environment; (iii) an addition of an organic solvent or a detergent to the environment; (iv) an addition of a metal chelating agent to the environment; and/or (v) a change in a temperature of the environment.

16. The PIX material of claim 1 , wherein the second stimulus includes one or more of: (i) a change in ionic strength of an environment comprising the PIX material; (ii) a change in a pH of the environment; (iii) an addition of an organic solvent or a detergent to the environment; (iv) an addition of a metal chelating agent to the environment; and/or (v) a change in a temperature of the environment.

17. The PIX material of claim 1 , wherein the crystal is a self-assembled protein crystal.

18. A method of controllably entrapping a molecular cargo within a material, comprising:

providing a reversibly-expandable polymer-integrated crystal (PIX) material in an environment containing molecules of the molecular cargo that includes a protein, a DNA, an RNA, or a nanoparticle, the reversibly-expandable polymer-integrated crystal (PIX) material, comprising:

a crystal comprising ferritin molecules organized in a crystal lattice, wherein the ferritin molecules are conjugated with a reversible addition-fragmentation chain-transfer (RAFT) agent; and

a polymer matrix comprising polyacrylate formed within the crystal lattice of the crystal such that the polymer matrix encompasses the ferritin molecules;

triggering an expansion of the PIX material by applying a first stimulus to the environment to cause the crystal lattice of the PIX material to expand;

loading the molecules of the molecular cargo within the expanded crystal lattice of the PIX material; and

entrapping the molecular cargo within the PIX material by triggering a contraction of the PIX material by applying a second stimulus to the environment to cause the crystal lattice of the PIX material to contract with the loaded molecules of the molecular cargo contained within the crystal lattice.

19. The method of claim 18 , wherein said loading the molecules of the molecular cargo within the expanded crystal lattice of the PIX material comprises allowing the molecules of the molecular cargo to permeate the polymer matrix of the PIX material from the environment.

20. The method of claim 18 , further comprising:

triggering another expansion of the PIX material by applying the first stimulus to the environment to cause the crystal lattice of the PIX material to re-expand; and

releasing the molecules of the molecular cargo from the re-expanded crystal lattice of the PIX material outside of the PIX material.

21. The method of claim 20 , wherein said releasing the molecules of the molecular cargo comprises allowing the molecules of the molecular cargo to diffuse from the PIX material into the environment.

22. The method of claim 20 , further comprising:

triggering another contraction of the PIX material by applying the second stimuli to the environment to cause the crystal lattice of the PIX material to re-contract.

23. The method of claim 18 , wherein the first stimulus and/or the second stimulus includes one or more of: (i) a change in ionic strength of an environment comprising the PIX material; (ii) a change in a pH of the environment; (iii) an addition of an organic solvent or a detergent to the environment; (iv) an addition of a metal chelating agent to the environment; and/or (v) a change in a temperature of the environment.

24. The method of claim 18 , wherein the second stimulus is different from the first stimulus.

25. A method of controllably entrapping a charged molecular cargo in a material, comprising:

providing a polymer-integrated crystal (PIX) material in an environment containing charged molecules of a molecular cargo that includes a protein, a DNA, an RNA, or a nanoparticle, the polymer-integrated crystal (PIX) material, comprising:

a crystal comprising ferritin molecules organized in a crystal lattice, wherein the ferritin molecules are conjugated with a reversible addition-fragmentation chain-transfer (RAFT) agent; and

a polymer matrix comprising polyacrylate formed within the crystal lattice of the crystal such that the polymer matrix encompasses the ferritin molecules,

wherein each molecule from the charged molecules has a first electric charge, and wherein the polymer matrix of the PIX material has a second electric charge having a sign opposite to a sign of the first electric charge;

keeping the PIX material in an environment for an amount of time without expanding the crystal lattice of the crystal of the PIX material; and

removing, without expanding the crystal lattice of the crystal of the PIX material, the PIX material from the environment immediately after said keeping the PIX material in the environment for the amount of time.

26. The method of claim 25 , wherein the protein includes at least one of lysozyme, cytochrome C, green fluorescent protein (GFP), bovine serum albumin (BSA), catalase, or streptavidin.

27. The method of claim 25 , wherein the polymer matrix includes a polyacrylate hydrogel.

28. The method of claim 25 , wherein the RAFT agent is a maleimide-functionalized trithiocarbonate RAFT agent.

29. The method of claim 18 , wherein the polymer matrix includes a polyacrylate hydrogel.

30. The method of claim 18 , wherein the RAFT agent is a maleimide-functionalized trithiocarbonate RAFT agent.

Assignments (2)
CONFIRMATORY LICENSE Recorded Aug 23, 2024
From: UNIVERSITY OF CALIFORNIA
To: U.S. DEPARTMENT OF ENERGY
Reel/Frame 068764/0239 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 31, 2023
From: TEZCAN, FAIK AKIF; ZHANG, LING; NA, YOUJEONG; HAN, KENNETH
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 064768/0943 →
Continuity (2)
Provisional Application 63116637 · Nov 20, 2020
Related Publication 20230331975A1 · Oct 19, 2023
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