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Polymer Cancerostatics Targeted with an Antibody Fragment Bound via a Coiled Coil Motif: In Vivo Therapeutic Efficacy against Murine BCL1 Leukemia
- Source :
- Macromolecular Bioscience. 18:1700173
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
Abstract
- A BCL1 leukemia-cell-targeted polymer-drug conjugate with a narrow molecular weight distribution consisting of an N-(2-hydroxypropyl)methacrylamide copolymer carrier and the anticancer drug pirarubicin is prepared by controlled radical copolymerization followed by metal-free click chemistry. A targeting recombinant single chain antibody fragment (scFv) derived from a B1 monoclonal antibody is attached noncovalently to the polymer carrier via a coiled coil interaction between two complementary peptides. Two pairs of coiled coil forming peptides (abbreviated KEK/EKE and KSK/ESE) are used as linkers between the polymer-pirarubicin conjugate and the targeting protein. The targeted polymer conjugate with the coiled coil linker KSK/ESE exhibits 4× better cell binding activity and 2× higher cytotoxicity in vitro compared with the other conjugate. Treatment of mice with established BCL1 leukemia using the scFv-targeted polymer conjugate leads to a markedly prolonged survival time of the experimental animals compared with the treatment using the free drug and the nontargeted polymer-pirarubicin conjugate.
- Subjects :
- Immunoconjugates
Polymers and Plastics
Polymers
Stereochemistry
Bioengineering
02 engineering and technology
010402 general chemistry
01 natural sciences
Biomaterials
Mice
chemistry.chemical_compound
Drug Delivery Systems
In vivo
Materials Chemistry
Animals
Humans
Methacrylamide
Cyclin D1
Molecular Targeted Therapy
Immunoglobulin Fragments
Coiled coil
Acrylamides
Drug Carriers
Leukemia
Chemistry
Antibodies, Monoclonal
021001 nanoscience & nanotechnology
0104 chemical sciences
Disease Models, Animal
Targeted drug delivery
Click chemistry
Click Chemistry
Peptides
0210 nano-technology
Drug carrier
Linker
Biotechnology
Conjugate
Subjects
Details
- ISSN :
- 16165187
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Macromolecular Bioscience
- Accession number :
- edsair.doi.dedup.....2fb8683fdc38cd25725216bafed86b51