Dual-targeted therapeutic peptide for nasopharyngeal carcinoma, nanoparticles carrying same and uses thereof

• US 9,371,364 B2
• Filed: 06/07/2013
• Issued: 06/21/2016
• Est. Priority Date: 06/07/2012
• Status: Active Grant

• Current Assignee: Huazhong University of Science & Technology
• Original Assignee: Huazhong University of Science & Technology
• Inventors: Luo, Qingming, Zhang, Zhihong, Luo, Haiming
• Primary Examiner(s): Russel, Jeffrey E
• Application Number:
  US14/406,399
• Publication Number:
  US 20150344525A1
• Time in Patent Office: 1,110 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/12 Ketones
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 38/10 Peptides having 12 to 20 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/16 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: A61K 47/6425 the peptide or protein in the drug conjugate being a receptor, e.g. CD4, a cell surface antigen, i.e. not a peptide ligand targeting the antigen, or a cell surface determinant, i.e. a part of the surface of a cell
• CPC Class Codes: A61K 47/65 Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
• CPC Class Codes: A61K 47/66 the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells
• CPC Class Codes: A61K 47/6929 the form being a nanoparticle, e.g. an immuno-nanoparticle
• CPC Class Codes: A61K 49/0093 Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle
• CPC Class Codes: A61K 9/5123 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5169 Proteins, e.g. albumin, gelatin
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/04 for throat disorders
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/4747 Apoptosis related proteins
• CPC Class Codes: C07K 14/4748 Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/33 fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
• CPC Class Codes: C07K 7/08 : having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68
• CPC Class Codes: G01N 33/57407 : Specifically defined cancers
• CPC Class Codes: G01N 33/582 : with fluorescent label

Abstract

Disclosed is a dual-targeted therapeutic peptide for nasopharyngeal carcinoma formed by covalently linking a targeted therapeutic peptide for nasopharyngeal carcinoma, a peptide linker and a targeted therapeutic peptide with an α-helical structure for nasopharyngeal carcinoma. Also disclosed is a nanoparticle containing the peptide. The peptide and the nanoparticle can be used to treat nasopharyngeal carcinoma.

Claims

1. A peptide for nasopharyngeal carcinoma, wherein the peptide for nasopharyngeal carcinoma is formed by covalently linking FAEKFKEAVKDYFAKFWD (SEQ ID NO:

2), a peptide linker and LTVSPWYLTVSPWY (SEQ ID NO;

3) in sequence.

2. The peptide for nasopharyngeal carcinoma according to claim 1, wherein the amino acid sequence of the peptide for nasopharyngeal carcinoma is:

3. A nanoparticle for nasopharyngeal carcinoma consisting of:

a peptide for nasopharyngeal carcinoma formed by covalently linking FAEKFKEAVKDYFAKFWD (SEQ ID NO;

2), a peptide linker and LTVSPWYLTVSPWY (SEQ ID NO;

3) in sequence;

a phospholipid;

a cholesteryl ester; and

a cargo.

4. The nanoparticle for nasopharyngeal carcinoma according to claim 3, wherein the cargo is an imaging contrast agent, a drug, or combinations thereof.

5. The nanoparticle for nasopharyngeal carcinoma according to claim 4, wherein the imaging contrast agent is a fluorescent dye modified with cholesteryl ester.

6. The nanoparticle for nasopharyngeal carcinoma according to claim 5, wherein the fluorescent dye is DiR-BOA or Fluo-BOA.

7. The nanoparticle for nasopharyngeal carcinoma according to claim 4, wherein the drug is paclitaxel or curcumin.

8. The nanoparticle for nasopharyngeal carcinoma according to claim 3, wherein the phospholipid is DMPC (1 ,2-dimyri stoyl-sn-glycero-3 -phosphocholine).

9. A method for diagnosis or treatment of nasopharyngeal carcinoma, comprising,

administering to a subject in need thereof a nanoparticle for nasopharyngeal carcinoma consisting of:

a peptide for nasopharyngeal carcinoma formed by covalently linking FAEKFKEAVKDYFAKFWD (SEQ ID NO;

2), a peptide linker and LTVSPWYLTVSPWY (SEQ ID NO;

3) in sequence;

a phospholipid;

a cholesteryl ester; and

a cargo.