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Polymer therapeutics with a coiled coil motif targeted against murine bcl1 leukemia
- Source :
- Biomacromolecules. 14(3)
- Publication Year :
- 2013
-
Abstract
- The specificity of polymer conjugates based on N-(2-hydroxypropyl)methacrylamide (HPMA) bearing cytostatic drugs for cancer cells could be significantly increased by the incorporation of a suitable targeting ligand, such as a monoclonal antibody (mAb). However, direct binding of the protein to the polymer carrier could cause considerable problems, such as decreasing the binding capacity of mAb to its target. Here, we introduce a novel strategy of joining a targeting moiety to a polymeric conjugate with cytostatic drug. The scFv of B1 mAb (specific for BCL1 leukemia cells) was tagged with peptide K ((VAALKEK)4). Peptide E ((VAALEKE)4), which forms a stable coiled coil structure heterodimer with peptide K, was assembled with the HPMA copolymers bearing doxorubicin. Such targeted polymeric conjugates possess very selective and high binding activity toward BCL1 cells. Similarly, targeted polymeric conjugates exert approximately 100 times higher cytostatic activity toward BCL1 cells in comparison to nontargeted conjugates in vitro. At the same time, the conjugates have comparable and rather low cytostatic activity for 38C13 cells, which are used as a negative control, in vitro.
- Subjects :
- Polymers and Plastics
medicine.drug_class
Polymers
Recombinant Fusion Proteins
Bioengineering
Peptide
Biocompatible Materials
Monoclonal antibody
Biomaterials
chemistry.chemical_compound
Mice
Cell Line, Tumor
Materials Chemistry
medicine
Moiety
Methacrylamide
Animals
Doxorubicin
Cell Proliferation
chemistry.chemical_classification
Coiled coil
Acrylamides
Drug Carriers
Mice, Inbred BALB C
Antibiotics, Antineoplastic
Leukemia
Antibodies, Monoclonal
Cytostatic Agents
Molecular biology
chemistry
Cancer cell
Biophysics
Methacrylates
Conjugate
medicine.drug
Subjects
Details
- ISSN :
- 15264602
- Volume :
- 14
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Biomacromolecules
- Accession number :
- edsair.doi.dedup.....d332a4b4b7040aa05ec177c15a40e663