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Self assembling molecules for targeted drug delivery

Inactive Publication Date: 2018-05-24
THE GENERAL HOSPITAL CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The invention is related to compositions and methods for treating cancer. The compositions comprise a protein, a first payload, and a first targeting agent that targets cancer cells. The first payload can be an anti-cancer agent or an imaging agent. The second compositions have the same components, but with the exception that they do not target cancer cells. The methods for treating cancer involve administering the composition to a subject in need and generating an image using the imaging agent. The technical effects of the invention include improved targeting of cancer cells and improved imaging of cancer cells.

Problems solved by technology

Many extremely useful chemotherapeutics lose their potential utility as effective cancer therapy due to their. systemic toxicity.
These agents have not achieved the versatility in chemical modification to provide for both long recirculation times and active targeting.
In addition, the use of targeted antibodies, immune-enhancing drugs, slow-release peptides, or polymers for targeted drug delivery results in extreme side-effects or low delivery efficiency (e.g, the delivery systems are not internalized by the cells).

Method used

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  • Self assembling molecules for targeted drug delivery
  • Self assembling molecules for targeted drug delivery
  • Self assembling molecules for targeted drug delivery

Examples

Experimental program
Comparison scheme
Effect test

example 1

n of Clathrin Heavy Chain

[0173]Clathrin human isoform 2 heavy chain was optimized for an E. coli expression system as follows:

(SEQ ID NO: 1):MAQILPIRFQEHLQLQNLGINPANIGFSTLTMESDKFICIREKVGEQAQVVIIDMNDPSNPIRRPISADSAIMNPASKVIALKAGKTLQIFNIEMKSKMKAHTMTDDVTFWKWISLNTVALVTDNAVYHWSMEGESQPVKMFDRHSSLAGCQIINYRTDAKQKWLLLTGISAQQNRVVGAMQLYSVDRKVSQPIEGHAASFAQFKMEGNAEESTLFCFAVRGQAGGKLHIIEVGTPPTGNQPFPKKAVDVFFPPEAQNDFPVAMQISEKHDVVFLITKYGYIHLYDLETGTCIYMNRISGETIFVTAPHEATAGIIGVNRKGQVLSVCVEEENIIPYITNVLQNPDLALRMAVRNNLAGAEELFARKFNALFAQGNYSEAAKVAANAPKGILRTPDTIRRFQSVPAQPGQTSPLLQYFGILLDQGQLNKYESLELCRPVLQQGRKQLLEKWLKEDKLECSEELGDLVKSVDPTLALSVYLRANVPNKVIQCFAETGQVQKIVLYAKKVGYTPDWIFLLRNVMRISPDQGQQFAQMLVQDEEPLADITQIVDVFMEYNLIQQCTAFLLDALKNNRPSEGPLQTRLLEMNLMHAPQVADAILGNQMFTHYDRAHIAQLCEKAGLLQRALEHFTDLYDIKRAVVHTHLLNPEWLVNYFGSLSVEDSLECLRAMLSANIRQNLQICVQVASKYHEQLSTQSLIELFESFKSFEGLFYFLGSIVNFSQDPDVHFKYIQAACKTGQIKEVERICRESNCYDPERVKNFLKEAKLTDQLPLIIVCDRFDFVHDLVLYLYRNNLQKYIEIYVQKVNPSRLPVVIGGLLDVDCSEDVIKNLILVVRGQFSTDELVAEVEKRNRLK...

example 2

n of Clathrin Light Chain

[0175]Clathrin light chain (below) was expressed in E. coli:

(SEQ ID NO: 4):MAELDPFGAPAGAPGGPALGNGVAGAGEEDPAAAFLAQQESEIAGIENDEAFAILDGGAPGPQPHGEPPGGPDAVDGVMNGEYYQESNGPTDSYAAISQVDRLQSEPESIRKWREEQMERLEALDANSRKQEAEWKEKAIKELEEWYARQDEQLQKTKANNRVADEAFYKQPFADVIGYVTNINHPCYSLEQAAEEAFVNDIDESSPGTEWERVARLCDFNPKSSKQAKDVSRMRSVLISLKQAPLVH(SEQ ID NO: 5):ATGGCGGAACTGGACCCGTTCGGCGCTCCGGCAGGCGCACCGGGCGGTCCGGCGCTGGGTAACGGCGTTGCGGGTGCTGGTGAAGAAGACCCGGCAGCAGCGTTCCTGGCGCAGCAGGAATCTGAAATCGCAGGTATCGAAAACGATGAAGCGTTCGCGATCCTGGACGGTGGTGCTCCGGGTCCGCAGCCGCACGGTGAACCGCCGGGTGGTCCGGATGCGGTTGACGGTGTTATGAACGGCGAGTACTACCAGGAGTCTAACGGTCCGACCGATTCTTACGCGGCAATTAGCCAGGTTGATCGTCTGCAaTCCGAACCGGAATCTATCCGTAAATGGCGTGAGGAGCAGATGGAACGCCTGGAAGCTCTGGACGCGAACTCTCGCAAACAGGAGGCGGAATGGAAAGAAAAAGCGATCAAAGAGCTGGAAGAATGGTATGCGCGTCAGGACGAACAGCTGCAaAAAACCAAAGCGAACAACCGTGTGGCGGACGAAGCATTCTACAAACAGCCGTTTGCGGACGTTATCGGTTACGTTACCAACATCAACCATCCGTGCTACTCTCTGGAGCAGGCAGCGGAAGAAGCgTTCGTGAACGACATCGACGAATCTAGCCCaGGcACCGAATGGG...

example 3

f Self-Assembled Protein

[0188]The self-assembled protein was loaded with a fluorescent compound to assess its ability to self-assembling following loading.

[0189]Recombinant clathrin heavy chain (HC) and light chain (LC) were diluted at 300 μg / mL and 800 μL / mL, respectively in 10 mM Tris-HCl (pH 7.9). A fluoresceinated test compound (FTC) was diluted at 500 μg / mL in the same buffer. Assembly of 100 μL in a 96-well assay plate was initiated by adding 4 μL of 1 M 2-(N-morpholino)ethanesulfonic acid (MES) buffer, pH 6.5 supplemented with 10 mM ethylene glycol tetraacetic acid (EGTA) and 75 mM CaCl2. A control was used with pH 7 MES buffer. OD320 nm readings were measured using the SpectraMax M3 (molecular devices) and the results were plotted by the software provided by the equipment.

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Abstract

Described herein are self-assembling protein molecules for delivering a payload, for example, a toxic anti-cancer agent, a cancer immunotherapy, a toxic anti-cancer agent and a cancer immunotherapy, or an imaging agent, to specific tissues. Examples of self-assembled proteins include clathrin and derivatives of clathrin.

Description

RELATED APPLICATIONS[0001]This application claims the benefit of priority to U.S. Provisional Patent Application Ser. No. 62 / 140,696, filed Mar. 31, 2015, the contents of which are hereby incorporated by reference.BACKGROUND[0002]Many extremely useful chemotherapeutics lose their potential utility as effective cancer therapy due to their. systemic toxicity. As a result, drug delivery systems have been a significant focus of research in the anti-cancer arena. For example, large particulate assemblies of biologically compatible materials, such as liposomes, have been used as carriers for administration of drugs and paramagnetic contrast agents. For example, liposome compositions containing an entrapped agent, such as a drug, are known; these compositions are engineered to control biodistribution and recirculatory half-life.[0003]In order to provide a therapeutic effect, a sufficient concentration of an active agent must be delivered to a targeted site. So, there is a need for recircul...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K9/50A61K31/337A61K31/7068A61K31/473A61K39/39A61K47/68A61P35/00A61K51/12A61K49/18A61K49/00
CPCA61K47/6949A61K47/6925A61K9/5052A61K31/337A61K31/7068A61K31/473A61K39/39A61K47/6849A61P35/00A61K51/1268A61K51/1251A61K49/189A61K49/1821A61K49/0091A61K49/0069A61K9/5169A61K47/62
Inventor ELMALEH, DAVID R.TAKAHASHI, KAZUE
Owner THE GENERAL HOSPITAL CORP
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