Short-chain cationic polyamino acid and use thereof

1. A cationic polyamino acid capable of associating with a nucleic acid, the cationic polyamino acid comprising:

1 to 20 units of one or more cationic amino acid residue(s) having a cationic group in a side chain; and

a plurality of hydrophobic amino acid residues having a hydrophobic group in a side chain,

wherein the cationic polyamino acid has the following formula (1):

where: R 1 is a hydroxyl group or an unsubstituted or substituted linear or branched alkyloxy group having 1 to 12 carbon atoms, an unsubstituted or substituted linear or branched alkenyloxy group having 2 to 12 carbon atoms, an unsubstituted or substituted linear or branched alkynyloxy group having 2 to 12 carbon atoms, or an unsubstituted or substituted linear or branched alkyl-substituted imino group having 1 to 12 carbon atoms;

R 2 is a hydrogen atom, an unsubstituted or substituted linear or branched alkyl group having 1 to 12 carbon atoms, or an unsubstituted or substituted linear or branched alkylcarbonyl group having 1 to 24 carbon atoms;

R 3a , R 3b , R 4a , and R 4b are each independently a methylene group or an ethylene group;

R 5a and R 5b are each independently —O— or —NH—;

R 6a and R 6b are each independently a saturated or unsaturated linear or branched aliphatic hydrocarbon group having 6 to 27 carbon atoms, an aromatic hydrocarbon group having 6 to 27 carbon atoms, or a sterol group derived from a sterol;

R 7a and R 7b are each independently selected from the group consisting of:

—NH—(CH 2 ) p1 —[NH—(CH 2 ) q1 —] r1 NH 2 (i);

—NH—(CH 2 ) p2 —N[—(CH 2 ) q2 —NH 2 ] 2 (ii);

—NH—(CH 2 ) p3 —N{[—(CH 2 ) q3 —NH 2 ][—(CH 2 ) q4 —NH—] r2 H} (iii); and

—NH—(CH 2 ) p4 —N{—(CH 2 ) q5 —N[—(CH 2 ) q6 —NH 2 ] 2 } 2 (iv),

where: p1 to p4, q1 to q6, and r1 and r2 are each independently an integer of 1 to 5;

R 8 is a side chain of an amino acid selected from the group consisting of lysine, ornithine, arginine, homoarginine, and histidine;

m is an integer of 5 to 80;

n is an integer of 0 to m;

x is an integer of 1 to 20;

y is an integer of 0 to x; and

z is an integer of 0 to 20,

with the proviso that:

1≦x+z≦20,

repeating units having the groups R 6a , R 6b , R 7a , and R 7b and R 8 may be bound to each other in any order, and

each of R 6a , R 6b , R 7a , R 7b and R 8 is arbitrarily selectable for each respective amino acid residue of the cationic polyamino acid.

2. The cationic polyamino acid according to claim 1 , wherein the cationic polyamino acid is a block polymer including a segment formed of a plurality of the cationic amino acid residue(s) and a segment formed of a plurality of the hydrophobic amino acid residues.

3. A polymer particle composition comprising a plurality of the cationic polyamino acids according to claim 1 bound to each other.

4. A complex comprising the cationic polyamino acid according to claim 1 bound to a nucleic acid.

5. The complex according to claim 4 , wherein the nucleic acid is siRNA.

6. The polymer particle composition according to claim 3 , further comprising a nucleic acid encapsulated within the polymer particle composition.

7. The polymer particle composition according to claim 6 , wherein the nucleic acid is siRNA.

8. A block copolymer capable of associating with a nucleic acid, the block copolymer comprising:

1 to 20 units of one or more cationic amino acid residue(s) having a cationic group in a side chain; and

a plurality of hydrophobic amino acid residues having a hydrophobic group in a side chain,

wherein the block copolymer has the following formula (1):

wherein: R 1 is a hydrophilic polymer chain segment;

R 2 is a hydrogen atom, an unsubstituted or substituted linear or branched alkyl group having 1 to 12 carbon atoms, or an unsubstituted or substituted linear or branched alkylcarbonyl group having 1 to 24 carbon atoms;

R 3a , R 3b , R 4a , and R 4b are each independently a methylene group or an ethylene group;

R 5a and R 5b are each independently —O— or —NH—;

R 6a and R 6b are each independently a saturated or unsaturated linear or branched aliphatic hydrocarbon group having 6 to 27 carbon atoms, an aromatic hydrocarbon group having 6 to 27 carbon atoms, or a sterol group derived from a sterol;

R 7a and R 7b are each independently selected from the group consisting of:

—NH—(CH 2 ) p1 —[NH—(CH 2 ) q1 —] r1 NH 2 (i);

—NH—(CH 2 ) p2 —N[—(CH 2 ) q2 —NH 2 ] 2 (ii);

—NH—(CH 2 ) p3 —N{[—(CH 2 ) q3 —NH 2 ][—(CH 2 ) q4 —NH—] r2 H} (iii); and

—NH—(CH 2 ) p4 —N{—(CH 2 ) q5 —N[—(CH 2 ) q6 —NH 2 ] 2 } 2 (iv),

wherein: p1 to p4, q1 to q6, and r1 and r2 are each independently an integer of 1 to 5;

R 8 is a side chain of an amino acid selected from the group consisting of lysine, ornithine, arginine, homoarginine, and histidine;

m is an integer of 5 to 80;

n is an integer of 0 to m;

x is an integer of 1 to 20;

y is an integer of 0 to x; and

z is an integer of 0 to 20,

with the proviso that:

1≦x+z≦20,

repeating units having the groups R 6a , R 6b , R 7a , and R 7b and R 8 may be bound to each other in any order, and

each of R 6a , R 6b , R 7a , R 7b and R 8 is arbitrarily selectable for each respective amino acid residue of the block copolymer acid.

9. The block copolymer according to claim 8 , wherein R 1 is poly(ethylene glycol), polysaccharide, poly(vinylpyrrolidone), poly(vinyl alcohol), poly(acrylic amide), poly(acrylic acid), poly(methacrylic amide), poly(methacrylic acid), poly(methacrylic acid ester), poly(acrylic acid ester), polyamino acid, poly(malic acid), or a derivative thereof.

10. A polymer particle composition comprising a plurality of the block copolymers according to claim 8 bound to each other.

11. A complex comprising the block copolymer according to claim 8 bound to a nucleic acid.

12. The complex according to claim 11 , wherein the nucleic acid is siRNA.

13. The polymer particle composition according to claim 10 , further comprising a nucleic acid encapsulated within the polymer particle composition.

14. The polymer particle composition according to claim 13 , wherein the nucleic acid is siRNA.

15. A block copolymer capable of associating with a nucleic acid, the block copolymer having a formula selected from the group consisting of the following formula (2) and formula (3):

wherein: R 1 is a hydroxyl group or an unsubstituted or substituted linear or branched alkyloxy group having 1 to 12 carbon atoms, an unsubstituted or substituted linear or branched alkenyloxy group having 2 to 12 carbon atoms, an unsubstituted or substituted linear or branched alkynyloxy group having 2 to 12 carbon atoms, or an unsubstituted or substituted linear or branched alkyl-substituted imino group having 1 to 12 carbon atoms;

R 2 is a hydrogen atom, an unsubstituted or substituted linear or branched alkyl group having 1 to 12 carbon atoms, or an unsubstituted or substituted linear or branched alkylcarbonyl group having 1 to 24 carbon atoms;

R 3a , R 3b , R 4a , and R 4b are each independently a methylene group or an ethylene group;

R 5a and R 5b are each independently —O— or —NH—;

R 6a and R 6b are each independently a saturated or unsaturated linear or branched aliphatic hydrocarbon group having 6 to 27 carbon atoms, an aromatic hydrocarbon group having 6 to 27 carbon atoms, or a steryl group derived from a sterol;

R 7a and R 7b are each independently selected from the group consisting of:

—NH—(CH 2 ) p1 —[NH—(CH 2 ) q1 —] r1 NH 2 (i);

—NH—(CH 2 ) p2 —N[—(CH 2 ) q2 —NH 2 ] 2 (ii);

—NH—(CH 2 ) p3 —N{[—(CH 2 ) q3 —NH 2 ][—(CH 2 ) q4 —NH—] r2 H} (iii); and

—NH—(CH 2 ) p4 —N{—(CH 2 ) q5 —N[—(CH 2 ) q6 —NH 2 ] 2 } 2 (iv),

wherein: p1 to p4, q1 to q6, and r1 and r2 are each independently an integer of 1 to 5;

R 8 is a side chain of an amino acid selected from the group consisting of lysine, ornithine, arginine, homoarginine, and histidine;

L 1 and L 3 are each independently —S—S— or a valence bond;

L 2 is —NH—, —O—, —O(CH 2 ) p1 —NH—, or —L 2a —(CH 2 ) q1 —L 2b —, wherein p1 and q1 are each independently an integer of 1 to 5, L 2a is OCO, OCONH, NHCO, NHCOO, NHCONH, CONH, or COO, and L 2b is NH or O;

L 4 is —OCO—(CH 2 ) p2 —CO—, —NHCO—(CH 2 ) p3 —CO—, or —L 4a —(CH 2 ) q2 —CO—, wherein p2, p3, and q2 are each independently an integer of 1 to 5 and L 4a is OCONH, —CH 2 NHCO—, NHCOO, NHCONH, CONH, or COO;

R 9 and R 10 are each independently a hydrogen atom or an unsubstituted or substituted linear or branched alkyl group having 1 to 12 carbon atoms;

k is an integer of 30 to 20,000;

m is an integer of 5 to 80;

n is an integer of 0 to m;

x is an integer of 1 to 20;

y is an integer of 0 to x; and

z is an integer of 0 to 20,

with the proviso that:

1≦x+z≦20,

repeating units having the groups R 6a , R 6b , R 7a , and R 7b and R 8 may be bound to each other in any order, and

each of R 6a , R 6b , R 7a , R 7b and R 8 is arbitrarily selectable for each respective amino acid residue of the block copolymer acid.

16. A polymer particle composition comprising a plurality of the block copolymers according to claim 15 bound to each other.

17. A complex comprising the block copolymer according to claim 15 bound to a nucleic acid.

18. The complex according to claim 17 , wherein the nucleic acid is siRNA.

19. The polymer particle composition according to claim 16 , further comprising a nucleic acid encapsulated within the polymer particle composition.

20. The polymer particle composition according to claim 19 , wherein the nucleic acid is siRNA.

21. A method of treating cancer, rheumatoid arthritis or retinitis, comprising:

intravenously administering to a patient in need thereof a therapeutically effective amount of the complex of claim 17 .

22. A method of treating cancer, rheumatoid arthritis or retinitis, comprising:

intravenously administering to a patient in need thereof a therapeutically effective amount of the complex of claim 11 .

23. A method of treating cancer, rheumatoid arthritis or retinitis, comprising:

intravenously administering to a patient in need thereof a therapeutically effective amount of the complex of claim 4 .