Cell penetrating peptides for intracellular delivery of molecules

1. A 10 amino acid cell-penetrating peptide characterized in that it comprises an amino acid sequence consisting of a beta-alanine or a serine in the N-terminal position, linked to a sequence consisting of 9 consecutive amino acids from the sequence

(SEQ ID NO: 7)

RXWXRLWXRLR,

wherein X in position 2 is R or S and X in positions 4 and 8 are, independently from each other, W or F.

2. The cell-penetrating peptide of claim 1 , wherein the amino acid sequence is selected from the group consisting of:

(SEQ ID No: 1)

X 1 WWRLWWRLR,

(SEQ ID No: 2)

X 1 WFRLWFRLR,

(SEQ ID No: 3)

X 1 WFRLWWRLR,

(SEQ ID No: 4)

X 1 WWRLWFRLR,

(SEQ ID No: 5)

X 1 RWWRLWWRL,

and

(SEQ ID No: 6)

X 1 RSWFRLWFR,

wherein X 1 is beta-A or S.

3. The cell-penetrating peptide of claim 1 , further comprising, covalently linked to the N-terminal end of the amino acid sequence, one or several chemical entities selected from the group consisting of an acetyl, a fatty acid, a cholesterol, a poly-ethylene glycol, a nuclear localization signal, a nuclear export signal, an antibody, a polysaccharide and a targeting molecule.

4. The cell-penetrating peptide of claim 1 , further comprising, covalently linked to the C-terminal end of said amino acid sequence, one or several groups selected from the group consisting of a cysteamide, a cysteine, a thiol, an amide, an optionally substituted nitrilotriacetic acid, a carboxyl, a linear or branched optionally substituted C 1 -C 6 alkyl, a primary or secondary amine, an osidic derivative, a lipid, a phospholipid a fatty acid, a cholesterol, a poly-ethylene glycol, a nuclear localization signal, a nuclear export signal, an antibody, a polysaccharide and a targeting molecule.

5. A complex comprising a cell-penetrating peptide according to claim 1 and a cargo selected from the group consisting of proteins, nanobodies, peptides, peptide-analogues, uncharged oligonucleotides, PNAs and small hydrophobic molecules.

6. The complex of claim 5 , wherein said cargo is a molecule of at most 1.5 kDa.

7. The complex of claim 5 , wherein said cargo is an anticancer or an anti viral drug.

8. The complex of claim 5 , wherein said cargo is selected from the group consisting of amino acids, di- or tri- peptides, daunomycin, Paclitaxel, doxorubicin, AZT, porphyrin, fluorescently labelled nucleosides or nucleotides, hydrophobic maghemite and fluorescent dyes.

9. The complex of claim 5 , wherein said cargo is a cosmetic agent.

10. The complex of claim 5 , wherein the size of the complex is between 50 and 200 nm.

11. A nanoparticle comprising a complex according to claim 5 , coated by a layer of peripheral cell-penetrating peptides, wherein said peripheral cell-penetrating peptides have a peptide sequence different from SEQ ID Nos: 1 to 6.

12. A nanoparticle comprising a core which comprises a cargo complexed to a first entity selected from the group consisting of cell-penetrating peptides, liposomes, polycationic structures and carbon nanoparticles, wherein said core is coated by peripheral cell-penetrating peptides, and wherein the peripheral cell-penetrating peptides have the peptide sequence of a cell-penetrating peptide according to claim 1 .

13. The nanoparticle of claim 12 , wherein said first entity is a cell-penetrating peptide selected from the group consisting of VEPEP-3, VEPEP-6, VEPEP-9, CADY, MPG, PEP-1, PPTG1, and poly Arginine.

14. The nanoparticle of claim 12 , wherein the size of the nanoparticle is between 20 and 300 nm.

15. The nanoparticle of claim 12 , wherein the peripheral cell-penetrating peptides comprise a poly-ethylene glycol group covalently linked to their N-terminus, and/or a cysteamide group covalently linked to their C-terminus.

16. The nanoparticle of claim 12 , wherein at least some of the peripheral cell-penetrating peptides are bound to a targeting molecule.

17. The nanoparticle of claim 12 , for use as a medicament.

18. The nanoparticle of claim 12 , for use as a marker or an imaging agent.

19. A therapeutic, cosmetic or diagnostic composition comprising a nanoparticle according to claim 12 .

20. The composition of claim 19 , which is formulated for intravenous, intratumoral, topical, intrarectal, intranasal, transdermal, or intradermal administration, or for administration via a mouth spray, or for administration as a subcutaneous implant for slow release of a drug.

21. A method for delivering a molecule into a cell in vitro, comprising a step of putting said cell into contact with a nanoparticle according to claim 12 , wherein the cargo of the nanoparticle is said molecule.