Self-assembled nanostructures of elastin- and resilin-based block copolypeptides with stimuli responsiveness and resilience for drug delivery system, tissue engineering and regenerative medicine and methods of preparing the same

1. A resilin-based polypeptide (RBP) exhibiting a phase transition behavior, which consists of the amino acid sequence of SEQ ID NO: 44.

2. The resilin-based polypeptide (RBP) according to claim 1 , which is encoded by the polynucleotide sequence of SEQ ID NO: 42.

3. A diblock polypeptide with a temperature responsiveness, represented by Formula 1, which consists of:

a resilin-based polypeptide block; and

an elastin-based polypeptide block exhibiting a phase transition behavior, which is connected to one end of the resilin-based polypeptide block:

[Formula 1]

[hydrophobic EBP] m -[RBP] n

wherein

n or m is independently an integer 1 or greater,

the [RBP] is a resilin-based polypeptide block consisting of the amino acid sequence of SEQ ID NO: 44, and

the [hydrophobic EBP] is an elastin-based polypeptide block selected from the group consisting of:

VPGXG VPGXG VPGXG VPGXG VPGXG VPGXG of SEQ ID NO: 1,

VPAXG VPAXG VPAXG VPAXG VPAXG VPAXG of SEQ ID NO: 2, and

IPAXG IPAXG IPAXG IPAXG IPAXG IPAXG of SEQ ID NO: 3; and

wherein:

i) when the [hydrophobic EBP] is the elastin-based polypeptide block of SEQ ID NO: 1, each X of the repeating pentapeptide consists of:

A (Ala), G (Gly) and I (Ile) at a ratio of 1:4:1;

K (Lys), G (Gly) and I (Ile) at a ratio of 1:4:1;

D (Asp), G (Gly) and I (Ile) at a ratio of 1:4:1;

E (Glu), G (Gly) and I (Ile) at a ratio of 1:4:1; or

G (Gly), A (Ala) and F (Phe) at a ratio of 1:3:2;

ii) when the [hydrophobic EBP] is the elastin-based polypeptide block of SEQ ID NO: 2, each X of the repeating pentapeptide consists of:

G (Gly), A (Ala) and F (Phe) at a ratio of 1:3:2;

K (Lys), A (Ala) and F (Phe) at a ratio of 1:3:2;

D (Asp), A (Ala) and F (Phe) at a ratio of 1:3:2;

K (Lys) and F (Phe) at a ratio of 3:3;

D (Asp) and F (Phe) at a ratio of 3:3;

H (His), A (Ala) and I (Ile) at a ratio of 3:2:1;

H (His) and G (Gly) at a ratio of 5:1; or

G (Gly), C(Cys) and F (Phe) at a ratio of 1:3:2; and

iii) when the [hydrophobic EBP] is the elastin-based polypeptide block of SEQ ID NO: 3, each X of the repeating pentapeptide consists of:

G (Gly), A (Ala) and F (Phe) at a ratio of 1:4:1; or

G (Gly), A (Ala) and F (Phe) at a ratio of 1:3:2.

4. The diblock polypeptide with a temperature responsiveness according to claim 3 , wherein when the [hydrophobic EBP] is a [VPGXG VPGXG VPGXG VPGXG VPGXG VPGXG] block of SEQ ID NO: 1, the [hydrophobic EBP] is SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 29, or SEQ ID NO: 31.

5. The diblock polypeptide with a temperature responsiveness according to claim 3 , wherein when the [hydrophobic EBP] is a [VPAXG VPAXG VPAXG VPAXG VPAXG VPAXG] block of SEQ ID NO: 2, the [hydrophobic EBP] is SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, or SEQ ID NO: 39.

6. The diblock polypeptide with a temperature responsiveness according to claim 3 , wherein when the [hydrophobic EBP] is an [IPAXG IPAXG IPAXG IPAXG IPAXG IPAXG] block of SEQ ID NO: 3, the [hydrophobic EBP] is SEQ ID NO: 40 or SEQ ID NO: 41.

7. The diblock polypeptide with a temperature responsiveness according to claim 3 , wherein the diblock polypeptide undergoes a dynamic change in response to temperature, and wherein

a [RBP] block core-[hydrophobic EBP] block shell micelle structure is formed through self-assembly at or below the lower critical solution temperature of the [hydrophobic EBP],

an aggregate is formed at or above the lower critical solution temperature of the [hydrophobic EBP], and

a [hydrophobic EBP] block core-[RBP] block shell micelle structure is formed at or above the upper critical solution temperature of the [RBP].

8. The diblock polypeptide with a temperature responsiveness according to claim 7 , wherein the dynamic change is reversible in response to temperature.

9. A drug delivery composition comprising the diblock polypeptide according to claim 3 .

10. A triblock polypeptide with a temperature responsiveness, represented by Formula 2, which consists of:

a resilin-based polypeptide block; and

elastin-based polypeptide blocks exhibiting a phase transition behavior, which are connected to both ends of the resilin-based polypeptide block:

[Formula 2]

[hydrophobic EBP] m -[RBP] n -[hydrophobic EBP] m

wherein

n or m is independently an integer 1 or greater,

the [RBP] is a resilin-based polypeptide block consisting of the amino acid sequence of SEQ ID NO: 44, and

the [hydrophobic EBP] is an elastin-based polypeptide block selected from the group consisting of:

VPGXG VPGXG VPGXG VPGXG VPGXG VPGXG of SEQ ID NO: 1,

VPAXG VPAXG VPAXG VPAXG VPAXG VPAXG of SEQ ID NO: 2, and

IPAXG IPAXG IPAXG IPAXG IPAXG IPAXG of SEQ ID NO: 3; and

wherein:

i) when the [hydrophobic EBP] is the elastin-based polypeptide block of SEQ ID NO: 1, each X of the repeating pentapeptide consists of:

A (Ala), G (Gly) and I (Ile) at a ratio of 1:4:1;

K (Lys), G (Gly) and I (Ile) at a ratio of 1:4:1;

D (Asp), G (Gly) and I (Ile) at a ratio of 1:4:1;

E (Glu), G (Gly) and I (Ile) at a ratio of 1:4:1; or

G (Gly), A (Ala) and F (Phe) at a ratio of 1:3:2;

ii) when the [hydrophobic EBP] is the elastin-based polypeptide block of SEQ ID NO: 2, each X of the repeating pentapeptide consists of:

G (Gly), A (Ala) and F (Phe) at a ratio of 1:3:2;

K (Lys), A (Ala) and F (Phe) at a ratio of 1:3:2;

D (Asp), A (Ala) and F (Phe) at a ratio of 1:3:2;

K (Lys) and F (Phe) at a ratio of 3:3;

D (Asp) and F (Phe) at a ratio of 3:3;

H (His), A (Ala) and I (Ile) at a ratio of 3:2:1;

H (His) and G (Gly) at a ratio of 5:1; or

G (Gly), C(Cys) and F (Phe) at a ratio of 1:3:2; and

iii) when the [hydrophobic EBP] is the elastin-based polypeptide block of SEQ ID NO: 3, each X of the repeating pentapeptide consists of:

G (Gly), A (Ala) and F (Phe) at a ratio of 1:4:1; or

G (Gly), A (Ala) and F (Phe) at a ratio of 1:3:2.

11. The triblock polypeptide with a temperature responsiveness according to claim 10 , wherein when the [hydrophobic EBP] is a [VPGXG VPGXG VPGXG VPGXG VPGXG VPGXG] block of SEQ ID NO: 1, the [hydrophobic EBP] is SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 29, or SEQ ID NO: 31.

12. The triblock polypeptide with a temperature responsiveness according to claim 10 , wherein when the [hydrophobic EBP] is a [VPAXG VPAXG VPAXG VPAXG VPAXG VPAXG] block of SEQ ID NO: 2, the [hydrophobic EBP] is SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, or SEQ ID NO: 39.

13. The triblock polypeptide with a temperature responsiveness according to claim 10 , wherein when the [hydrophobic EBP] is an [IPAXG IPAXG IPAXG IPAXG IPAXG IPAXG] block of SEQ ID NO: 3, the [hydrophobic EBP] is SEQ ID NO: 40 or SEQ ID NO: 41.

14. A hydrogel prepared by a process comprising:

applying a temperature, which is at or above the lower critical solution temperature of the [hydrophobic EBP], to the triblock polypeptide according claim 10 , wherein the triblock polypeptide undergoes self-assembly and phase transition to form a physically crosslinked network.

15. The hydrogel according to claim 14 , wherein the hydrogel undergoes reversible sol-gel or gel-sol transition in response to temperature.

16. The hydrogel according to claim 14 , wherein the hydrogel has enhanced mechanical strength due to chemical crosslinkages between the tyrosine residues of the resilin-based polypeptide block.

17. A composition for drug delivery comprising the hydrogel according to claim 14 .

18. A scaffold for tissue engineering comprising the hydrogel according to claim 14 .

19. A kit for tissue or organ regeneration comprising the hydrogel according to claim 14 .