Granted Patent
B2
US 12,594,347 · App. 17/272,887 · Granted Apr 7, 2026
Nanoparticulate drug delivery systems
Assignee:
Duke University
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Abstract
Described herein are compositions that include an assembly of self-assembling conjugates. The self-assembling conjugates may include a polypeptide having a transition temperature (17) above 50° C. when the polypeptide is not attached to the conjugate, an albumin binding domain (ABD) attached to a first end of the polypeptide, and at least one molecule attached to a second end of the polypeptide through a cysteine group, wherein the molecule has an octanol-water distribution coefficient (log D) of greater than or equal to 1.5 at a pH of 7.4 when the molecule is not attached to the conjugate. Also described herein are methods of using the compositions.
Claims (25)
1 . A composition comprising:
an assembly of self-assembling conjugates, each self-assembling conjugate comprising
a polypeptide having a transition temperature (T t ) above 50° C. when the polypeptide is not attached to the conjugate, wherein the polypeptide comprises an amino acid sequence of (X 1 GVPG) m (SEQ ID NO: 3), wherein X 1 is A or V: A: G at a ratio of 1:7:8 and m is 160 and wherein the polypeptide comprises an amino acid sequence of (CGG), (SEQ ID NO:4) at its C-terminus, wherein z is 1 to 40;
an albumin binding domain (ABD) attached to a first end of the polypeptide's N-terminus, wherein the ABD comprises an amino acid sequence of SEQ ID NO: 6; and
at least one molecule attached to a thiol group of an individual cysteine of SEQ ID NO:4 through a linker, wherein the molecule is a chemotherapeutic or an imaging agent, and wherein the molecule has an octanol-water distribution coefficient (logD) of greater than or equal to 1.5 at a pH of 7.4 when the molecule is not attached to the conjugate,
wherein the conjugate has a T t above 40° C. at a concentration of 100 uM.
2 . A composition comprising:
an assembly of self-assembling conjugates, each self-assembling conjugate comprising
a polypeptide having a transition temperature (T t ) above 50° C. when the polypeptide is not attached to the conjugate, wherein the polypeptide comprises an amino acid sequence of (X 1 GVPG) m (SEQ ID NO: 3), wherein X 1 is A or V: A: G at a ratio of 1:7:8 and m is 160 and wherein the polypeptide comprises an amino acid sequence of (CGG), (SEQ ID NO:4) at its C-terminus, wherein z is 1 to 40;
an albumin binding domain (ABD) attached to the polypeptide's N-terminus, wherein the ABD attached to the polypeptide lowers the T t of the polypeptide no more than 5° C. relative to the polypeptide's T t when the polypeptide is not attached to the ABD or the conjugate, and wherein the ABD comprises an amino acid sequence of SEQ ID NO:6; and
at least one molecule attached to a thiol group of an individual cysteine of SEQ ID NO:4 through a linker, wherein the molecule is a chemotherapeutic or an imaging agent, and wherein the molecule has an octanol-water distribution coefficient (logD) of greater than or equal to 1.5 at a pH of 7.4 when the molecule is not attached to the conjugate.
3 . The composition of claim 1 , wherein the polypeptide comprises an amino acid sequence of (CGG) 8 (SEQ ID NO:5) at its C-terminus.
4 . The composition of claim 1 , wherein about 1 to about 15 molecules are attached to the polypeptide.
5 . The composition of claim 1 , wherein the assembly of self-assembling conjugates is a nanoparticle.
6 . The composition of claim 1 , wherein the molecule is located in a core of the nanoparticle.
7 . The composition of claim 5 , wherein the nanoparticle has an average hydrodynamic radius of about 10 nm to about 100 nm.
8 . The composition of claim 5 , wherein the nanoparticle is a micelle.
9 . A method of treating a cancer in a subject comprising administering to the subject the composition of claim 1 wherein the cancer is breast cancer, colon cancer or combination thereof.
10 . A method of localizing a molecule to a tissue or organ in a subject, the method comprising administering to the subject the composition of claim 1 , wherein following administration of the composition the amount of the molecule localized in the tissue or organ is decreased when compared to the molecule in a self-assembling conjugate without an albumin binding domain and wherein the tissue or organ is a kidney, liver, spleen or any combination thereof.
11 . The method of claim 10 , wherein the amount of the molecule localized in the tissue or organ is decreased at least two-fold.
12 . A method of localizing a molecule to a tumor in a subject, the method comprising administering to the subject the composition of claim 1 , wherein following administration of the composition the amount of the molecule localized to the tumor is increased when compared to the molecule in a self-assembling conjugate without an albumin binding domain.
13 . The method of claim 12 , wherein the amount of the molecule localized to the tumor is increased at least two-fold.
14 . The composition of claim 1 , wherein the linker comprises a haloacetyl, a maleimide, a hydrazide, an aziridines, an acryloyl, or a combination thereof.
15 . The composition of claim 1 , wherein the molecule is a chemotherapeutic and the linker is a pH dependent linker.
16 . The composition of claim 15 , wherein the chemotherapeutic is attached to the linker through a hydrazone linkage.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 2, 2021
From: YOUSEFPOUR, PARISA; CHILKOTI, ASHUTOSH
To: DUKE UNIVERSITY
Reel/Frame 055464/0822 →
Continuity (2)
Provisional Application
62728582
· Sep 7, 2018
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