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Formation of Functionalized Nanoparticles By Supramolecular Co-assembly
| Content Provider | The Lens |
|---|---|
| Description | La présente invention concerne des conjugués de nanoparticules intégrant le module d'auto-assemblage dipeptide diphénylalanine (FF) dans une fraction bioactive. Le conjugué s'assemble spontanément pour former des structures nanométriques distinctes, par exemple des nanosphères. La présente invention concerne en outre des nanoparticules formées par co-assemblage supramoléculaire des conjugués avec un dipeptide diphénylalanine (FF) ou un analogue correspondant, pour générer des nanostructures bioactives auto-assemblées. |
| Abstract | The present invention provides nanoparticle conjugates incorporating the self- assembling module diphenylalanine (FF) dipeptide into a bioactive moiety. The conjugate self-assembles to form distinct nanometric structures such as nanospheres. The present invention further provides nanoparticles formed by supramolecular co- assembly of the conjugates with a diphenylalanine (FF) dipeptide or analog thereof, to generate bioactive self-assembled nanostructures. |
| Related Links | https://www.lens.org/lens/patent/013-486-591-470-746/frontpage |
| Language | English |
| Publisher Date | 2017-07-27 |
| Access Restriction | Open |
| Alternative Title | Formation De Nanoparticules Fonctionnalisées Par Co-assemblage Supramoléculaire |
| Content Type | Text |
| Resource Type | Patent |
| Date Applied | 2017-01-19 |
| Agent | Webb, Cynthia Et Al. |
| Applicant | Ramot At Tel-aviv Univ Ltd Tel Hashomer Medical Res Infrastructure & Services Ltd |
| Application No. | 2017050080 |
| Claim | CLAIMS What is claimed is: A nanoparticle comprising a self- assembled conjugate of a diphenylalanine (FF) dipeptide or analog thereof, covalently bound, directly or through a linker, to a bioactive moiety selected from the group consisting of a therapeutically active agent, a biological substance, a cosmetic agent, a cell targeting moiety, a labelling moiety, a radioactive moiety, an imaging agent and a diagnostic agent. The nanoparticle according to claim 1 , wherein the diphenylalanine (FF) dipeptide or analog thereof is diphenylalanine (FF) or a protected diphenylalanine (FF). The nanoparticle according to claim 2, wherien the protected diphenylalanine is an amino -protected diphenylalanine (FF) selected from the group consisting of 9-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF), t-butoxycarbonyl- diphenylalanine (Boc-FF), benzyloxycarbonyl (Cbz) diphenylalanine (Cbz-FF), acyl-diphenylalanine (Ac-FF), and silyl phenylalanine (silyl-FF). The nanoparticle according to claim 1 , wherein the diphenylalanine (FF) dipeptide or analog thereof is conjugated to the bioactive moiety through a linker. The nanoparticle according to claim 4, wherein the linker is selected from the group consisting of: a linear or branched C1-C20 alkylene, C2-C20 alkenylene, C2-C20 alkynylene and arylene moiety, each of which optionally incoprorates one or more heteroatoms selected from O, N and S in the chain, and which is optionally substituted at either or both ends with a group selected from the group consisting of -NH-, -C(=0)-, -0-, -S-, -C(=0)-0-, -0-C(=0)-0-, - C(=0)-NH-, -NH-C(=0)-NH-, NH-C(=0)-0-, -S(=0)-, -S(=0)-0-, -PO(=0)- 0-, and any combination thereof. The nanoparticle according to claim 4 or 5, wherein the linker is derived from polyethylene glycol (PEG). The nanoparticle according to claim 6 , wherein the linker is represented by the structure: The nanoparticle according to claim 1, wherein the bioactive moiety is selected from the group consisting of hormones, drugs, peptides, polypeptides, proteins, enzymes, growth factors, nucleic acids, microorganisms, fluorescence compounds or moieties, phosphorescence compounds or moieties, radioactive compounds or moieties, inorganic nanoparticles useful for biological applications and any combinations thereof. The nanoparticle according to claim 1 , wherein the active moiety is an anticancer drug. The nanoparticle according to claim 8 or 9, wherein the active moiety a hormone or hormone analog. The nanoparticle according to claim 10, wherein the hormone analog is somatostatin or a somatostatin analog. The nanoparticle according to claim 1 , having a diameter between about 50 nm and about 250 nm. The nanoparticle according to any one of the preceding claims, which is in a form selected from the group consisting of nanospheres, nanotubes, nanofibrils and ribbon-like nanostructures. A nanoparticle formed by supramolecular co-assembly of the self-assembled conjugate according to claim 1 , and a diphenylalanine (FF) dipeptide or analog thereof. The nanoparticle according to claim 14, wherein the diphenylalanine (FF) dipeptide or analog thereof is co-assembled with the conjugate through non- covalent interactions. The nanoparticle according to claim 14, wherein the ratio between the conjugate and the diphenylalanine (FF) dipeptide or analog thereof is about 1 to about 10, preferably about 1 to about 4. The nanoparticle according to claim 14, wherein the diphenylalanine (FF) or analog thereof is diphenylalanine (FF) or a protected diphenylalanine (FF) selected from the group consisting of an amino-protected diphenylalanine (FF), a carboxy-protected diphenylalanine (FF), an amino-protected, carboxy- protected diphenylalanine (FF), and combinations thereof. The nanoparticle according to claim 17, wherein the amino-protected diphenylalanine is selected from the group consisting of t-butoxycarbonyl- diphenylalanine (Boc-FF), 9-fiuorenylmethoxycarbonyl diphenylalanine (Fmoc-FF), benzyloxycarbonyl (Cbz) diphenylalanine (Cbz-FF), acyl- diphenylalanine (Ac-FF), and silyl phenylalanine (silyl-FF). The nanoparticle according to claim 14, having a diameter between about 50 nm to about 250 nm. The nanoparticles according to any one of claims 14 to 19, which is in a form selected from the group consisting of nanospheres, nanotubes, nanofibrils ribbon-like nanostructures. A pharmaceutical composition comprising the nanoparticle according to any one of the preceding claims, and a pharmaceutically or cosmetically acceptable carrier. A nanoparticle according to any one of the preceding claims, for use for the delivery of drugs. A nanoparticle according to any one of the preceding claims, for use as a targeting agent for delivery of anti-cancer drugs to a target tumor. A nanoparticle according to any one of the preceding claims, for use as an imaging agent. Use of diphenylalanine (FF) or an analog thereof, for assembling a peptide, polypeptide or protein into a nanometric structure so as to enhance the half-life of said peptide, polypeptide or protein in a biological sample. The use according to claim 25, wherein the diphenylalanine (FF) or analog thereof is Fmoc-FF or Boc-FF, which is used to enhance the half- life of a protein in the body of a subject. A nanoparticle according to claim 1 , comprising somatostatin or a somatostatin analog covalently conjugated to a FF dipeptide or FF dipeptide analog, directly or through a linker. The nanoparticle according to claim 27, which is represented by the structure: FF-(PEG) 2 -PTR wherein PTR is somatostatin or analog thereof, FF is diphenylalanine or analog ker represented by the structure The nanoparticle according to claim 28, which is represented by the structure depicted in Figure la. Fmoc-FF-(PEG) 2 -PTR wherein PTR is somatostatin or analog thereof, Fmoc-FF is 9- fluorenylmethox 2 is a linker represented by the structure The nanoparticle according to claim 30, which is represented by the structure depicted in Figure lb. The nanoparticle according to any one of claims 27 to 31, for use as a delivery system of chemotherapy to a target tumor. The nanoparticle according to claim 32, for use as a delivery system of chemotherapy in pancreatic cancer. A nanoparticle according to claim 27, co -assembled with FF or a FF analog. The nanoparticle according to claim 34, which is represented by the structure: Fmoc-FF-(PEG) 2 -PTR:Boc-FF (1 :4) wherein PTR is somatostatin or analog thereof, Fmoc-FF is 9- fluorenylmethoxycarbonyl diphenylalanine, Boc-FF is t-butoxycarbonyl diphenylalanine, and (PEG)2 is a linker derived from polyethylene glycol having the structu , and wherein Fmoc- FF-(PEG)2-PTR is represented by the structures as depicted in Figure lb. The nanoparticle according to claim 34 or 35, for use as a delivery system of chemotherapy to a target tumor. The nanoparticle according to claim 36, for use as a delivery system of chemotherapy in pancreatic cancer. A method of preparing the nanoparticle according to claim 1 , the method comprising the step of covalently conjugating a bioactive moiety, directly or through a linker, to diphenylalanine (FF) dipeptide or analog thereof, under conditions sufficient to form a self-assembled conjugate. A method of preparing the nanoparticle according to claim 14, the method comprising the steps of: (a) covalently conjugating said active moiety, directly or through a linker, to diphenylalanine (FF) dipeptide or analog thereof, under conditions sufficient to form a self-assembled conjugate; and (b) contacting the product of step (a) with diphenylalanine (FF) dipeptide or analog thereof, under conditions sufficient to form a supramolecular structure, wherein the diphenylalanine (FF) or analog thereof is co-assembled with the conjugate of step (a) through non-covalent interactions. |
| CPC Classification | Preparations For Medical; Dental Or Toiletry Purposes SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES;MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES;MANUFACTURE OR TREATMENT OF NANOSTRUCTURES PEPTIDES Specific Therapeutic Activity Of Chemical Compounds Or Medicinal Preparations |
| Extended Family | 013-486-591-470-746 177-047-018-911-169 001-165-243-852-147 045-737-357-065-843 121-072-066-755-263 130-739-162-919-749 |
| Patent ID | 2017125933 |
| Inventor/Author | Shekhter Zahavi Talia Gazit Ehud Herman-oron Mor Kostenich Genady Orenstein Arie |
| IPC | B82Y5/00 A61K9/14 A61K47/42 C07K5/00 C07K11/02 |
| Status | Pending |
| Simple Family | 013-486-591-470-746 177-047-018-911-169 001-165-243-852-147 045-737-357-065-843 121-072-066-755-263 130-739-162-919-749 |
| CPC (with Group) | A61K47/64 A61K47/6935 B82Y5/00 B82Y40/00 C07K5/06078 A61K47/6929 A61K38/31 A61K47/60 A61P35/00 |
| Issuing Authority | United States Patent and Trademark Office (USPTO) |
| Kind | Patent Application Publication |
