Amphiphilic polynucleotides
Compositions and methods disclosed herein can help provide improved delivery of non-natural therapeutic nucleotides for the treatment of diseases such as cancer. An example composition includes an assembly of amphiphilic polynucleotides, where each amphiphilic polynucleotide includes an aptamer portion, a first nucleotide portion, and a second nucleotide portion.
1. A composition comprising an assembly of amphiphilic polynucleotides, each amphiphilic polynucleotide being single-stranded and comprising, in a 5′ to 3′ direction,
an aptamer portion;
a first nucleotide portion comprising a nucleotide sequence of (FdUTP) m (SEQ ID NO:9), wherein m is 100 to 2,000; and
a second nucleotide portion comprising a nucleotide sequence of (Y 1 ) n (SEQ ID NO:11), wherein Y 1 is a non-natural hydrophobic nucleotide including a base having a Log P≥1.95, and n is 2 to 10.
2. The composition of claim 1 , wherein the aptamer portion comprises about 15 to about 100 nucleotides.
3. The composition of claim 1 , wherein the aptamer portion is capable of binding to a surface protein overexpressed in a cancer cell.
4. The composition of claim 1 , wherein the aptamer portion comprises an aptamer and a linker.
5. The composition of claim 4 , wherein the aptamer is selected from the group consisting of (SEQ ID NO:1), (SEQ ID NO:2), (SEQ ID NO:3), (SEQ ID NO:4), (SEQ ID NO:5), and (SEQ ID NO:6).
6. The composition of claim 1 , wherein m is 300 to 1,000.
7. The composition of claim 1 , wherein the first nucleotide portion further comprises a nucleotide sequence of (Z 1 ) p (SEQ ID NO:10), wherein Z 1 is a non-natural nucleotide having an amino group, an alkynyl group, an azide group, or a combination thereof, and p is 5 to 80.
8. The composition of claim 1 , wherein the non-natural hydrophobic nucleotide is selected from the group consisting of Atto-dUTP, BODIPY-dUTP, and a combination thereof.
9. The composition of claim 1 , wherein the first nucleotide portion and the second nucleotide portion are included at a ratio (number of nucleotides of the first nucleotide portion: number of nucleotides of the second nucleotide portion) of about 20:1 to about 60:1.
10. The composition of claim 1 , wherein the amphiphilic polynucleotide comprises about 300 to about 600 nucleotides.
11. The composition of claim 1 , wherein the amphiphilic polynucleotide has a critical micelle concentration of ≤0.1 μM.
12. The composition of claim 1 , wherein the assembly is stable in a mixture of about 50% fetal bovine serum for about 30 minutes to about 1 day.
13. The composition of claim 1 , wherein the assembly of amphiphilic polynucleotides is a nanoparticle.
14. The composition of claim 13 , wherein the nanoparticle has an average hydrodynamic radius of about 20 nm to about 125 nm.
15. The composition of claim 13 , wherein the nanoparticle is a micelle.