Polymer Cancerostatics Targeted with an Antibody Fragment Bound via a Coiled Coil Motif: In Vivo Therapeutic Efficacy against Murine BCL1 Leukemia
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- cancer therapy, coiled coil, drug targeting, hydrophilic polymer, scFv,
- MeSH
- Acrylamides chemistry MeSH
- Molecular Targeted Therapy MeSH
- Cyclin D1 antagonists & inhibitors immunology MeSH
- Immunoglobulin Fragments administration & dosage immunology MeSH
- Immunoconjugates administration & dosage chemistry MeSH
- Leukemia immunology pathology therapy MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Antibodies, Monoclonal chemistry immunology MeSH
- Mice MeSH
- Drug Carriers administration & dosage chemistry MeSH
- Peptides chemistry immunology MeSH
- Polymers administration & dosage chemistry MeSH
- Click Chemistry MeSH
- Drug Delivery Systems MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acrylamides MeSH
- Cyclin D1 MeSH
- Immunoglobulin Fragments MeSH
- Immunoconjugates MeSH
- Antibodies, Monoclonal MeSH
- N-(2-hydroxypropyl)methacrylamide MeSH Browser
- Drug Carriers MeSH
- Peptides MeSH
- Polymers MeSH
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.
References provided by Crossref.org
