Tumor cell-specific responsive self-assembling drug nanoconjugate

Patent metadata

Field	Value
Publication number	US-10610602-B2
Application number	US-201815925830-A
Country	US
Kind code	B2
Filing date	Mar 20, 2018
Priority date	Sep 20, 2017
Publication date	Apr 7, 2020
Grant date	Apr 7, 2020

Abstract

Disclosed is a drug conjugate as a prodrug that is degraded by cathepsin B specifically expressed in tumor tissues to release doxorubicin. The drug conjugate can form self-assembled nanoparticles. In addition, the drug conjugate specifically responds to and is activated in tumor cells. Therefore, the use of the drug conjugate eliminates the incidence of side effects (for example, cell damage and apoptosis) during the course of cancer prevention or treatment.

First claim

What is claimed is:

1. A low molecular weight drug conjugate, consisting of:
an amphiphilic peptide having the sequence set forth in any one of SEQ ID NOS: 1 to 4; and
a hydrophobic drug,
wherein the amphiphilic peptide is directly conjugated to the hydrophobic drug without a linker,
wherein the hydrophobic drug is selected from the group consisting of taxol, bendamustine, busulfan, carmustine, chlorambucil, cyclophosphamide, dacarbazine, adriamycin, daunomycin, ifosfamide, melphalan, procarbazine, streptozocin, temozolomide, asparaginase, capecitabine, cytarabine, 5-fluorouracil, fludarabine, gemcitabine, methotrexate, pemetrexed, raltitrexed, actinomycin-D, bleomycin, daunorubicin, doxorubicin, pegylated liposomal doxorubicin, epirubicin, idarubicin, mitomycin, mitoxantrone, etoposide, docetaxel, irinotecan, paclitaxel, topotecan, vinblastine, vincristine, vinorelbine, carboplatin, cisplatin, oxaliplatin, alemtuzumab, BCG, bevacizumab, cetuximab, denosumab, erlotinib, gefitinib, imatinib, interferon, ipilimumab, lapatinib, panitumumab, rituximab, sunitinib, sorafenib, temsirolimus, trastuzumab, clodronate, ibandronic acid, pamidronate, and zoledronic acid, and
wherein the conjugate is cleavable by cathepsin B to release the hydrophobic drug.

2. The drug conjugate according to claim 1 , wherein the drug conjugate has a molecular weight of 800 to 3000 Da.

3. Spherical self-assembled nanoparticles spontaneously formed by the drug conjugate according to claim 1 in a solvent and having a structure in which hydrophobic moieties of the drug conjugate form a core and hydrophilic moieties of the drug conjugate are exposed to the outside of the core.

4. The self-assembled nanoparticles according to claim 3 , wherein the solvent is selected from the group consisting of distilled water, phosphate buffered solution (PBS), physiological saline, distilled water containing 0.5 to 1% NaCl, and phosphate buffered solution (PBS) containing 0.5 to 1% NaCl.

5. The self-assembled nanoparticles according to claim 3 , wherein the self-assembled nanoparticles have an average diameter of 50 to 500 nm.

Assignees

• Korea Inst Sci & Tech

Inventors

• Kim Kwangmeyung
• Kwon Ick Chan
• Park Juho

Classifications

• A61K31/704 Primary

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title

• A61K47/65

  Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers · CPC title

• A61K47/6929

  the form being a nanoparticle, e.g. an immuno-nanoparticle · CPC title

• A61K45/00

  Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00 · CPC title

• A61K47/67 Primary

  Enzyme prodrug therapy, e.g. gene directed enzyme drug therapy [GDEPT] or VDEPT · CPC title