Methods and constructs for compound delivery

Patent metadata

Field	Value
Publication number	US-2016263137-A1
Application number	US-201415031151-A
Country	US
Kind code	A1
Filing date	Oct 20, 2014
Priority date	Oct 21, 2013
Publication date	Sep 15, 2016
Grant date	—

Abstract

A construct for selectively delivering a compound of interest to a cell, includes (a) a bioresorbable polymer shell; (b) a nucleic acid duplex contained in said shell, the duplex comprising (i) an ATP binding nucleic acid, and (ii) a complementary nucleic acid hybridized to the ATP binding nucleic acid; (c) a compound of interest intercalated in or caged by the nucleic acid duplex; (d) optionally, but in some embodiments preferably, a cationic polymer in said polysaccharide shell; and (e) optionally, but in some embodiments preferably, a cell targeting ligand coupled to the polymer shell. The polymer shell is degraded in a cell of interest, or in the extracellular matrix of a tissue carrying said cell of interest, to release said duplex therein. The wherein said duplex is destabilized by binding of ATP in the cell of interest to release the compound of interest therein.

First claim

1 . A construct for selectively delivering a compound of interest to a cell, comprising:
(a) a bioresorbabie polymer shell; (b) a nucleic acid duplex contained in said shell, said duplex comprising (i) an ATP binding nucleic acid, and (ii) a complementary nucleic acid hybridized to said ATP binding nucleic acid; (c) a compound of interest intercalated in or caged by said nucleic acid duplex; (d) optionally, a cationic polymer in said polysaccharide shell; and (e) optionally, a cell targeting ligand coupled to said polymer shell; wherein said polymer shell is degraded in a cell of interest, or in the extracellular matrix of a tissue carrying said cell of interest, to release said duplex therein; and wherein said duplex is destabilized by binding of ATP in said cell of interest to release said compound of interest therein.

2 . The construct of claim 1 , wherein said bioresorbable polymer shell comprises a crosslinked polymer or copolymer of a polyacrylic acid, polymethacrylic acid, polyethylene amine, a polysaccharide, alginic acid, a pectinic acid, carboxy methyl cellulose, hyaluronic acid, heparin, chitosan, carboxymethyl chitosan, carboxymethyl starch, carboxymethyl dextran, heparin sulfate, chondroitin sulfate, cationic starch, or salts thereof.

3 . The construct of claim 1 , wherein said bioresorbable polymer shell has an average diameter of from 1 or 10 nanometers to 500 or 1000 nanometers.

4 . The construct of claim 1 , wherein said ATP binding nucleic acid comprises, an ATP binding aptamer.

5 . The construct of claim 1 , wherein said complementary nucleic acid comprises DNA.

6 . The construct of claim 1 , wherein said compound of interest is a detectable compound or a cytotoxic compound.

7 . The construct of claim 1 , wherein said compound of interest comprises a DNA intercalating agent.

8 . The construct of claim 7 , wherein said intercalating agent comprises doxorubicin, daunorubicin, epirubicin, idarubicin, valrubicine, mitoxantrone, or a combination thereof.

9 . The construct of claim 1 , wherein said cationic polymer is present.

10 . The construct of claim 1 , wherein said cell-targeting ligand is present.

11 . A composition comprising a construct of claim 1 in a pharmaceutically acceptable carrier.

12 . A method of delivering a compound of interest to a cell, comprising the steps of:
(a) providing a construct of claim 1 ; and (b) contacting said construct to said cell or a tissue carrying said cell, under conditions in which said compound of interest is released therefrom.

13 . The method of claim 12 , wherein said cell or tissue comprises mammalian cell or tissue.

14 . The method of claim 12 , wherein said contacting step is carried out in vitro.

15 . The method of claim 12 , wherein said contacting step is carried out in vivo.

16 . A method of treating cancer in a subject in need thereof, comprising administering said subject a construct of claim 1 in a treatment effective amount, wherein said compound of interest comprises an anticancer or antineoplastic agent.

17 . The method of claim 16 , wherein said cancer is lung, skin, prostate, breast, ovarian, endometrial, colorectal, pancreatic, kidney, bladder, liver, or brain cancer, or leukemia or lymphoma.

18 - 37 . (canceled)

Assignees

• Univ North Carolina State

Inventors

• Gu Zhen
• Mo Ran
• Jiang Tianyue

Classifications

• A61K9/5123

  Organic compounds, e.g. fats, sugars · CPC title

• A61K9/5161

  Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin · CPC title

• A61K31/704 Primary

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title

• C12N2320/32

  Special delivery means, e.g. tissue-specific · CPC title

• C12N2320/31

  Combination therapy · CPC title