1. Cell Uptake and Trafficking Behavior of Non-covalent, Coiled-coil Based Polymer-Drug Conjugates
- Author
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Apostolovic, Bojana, Deacon, Samuel P. E., Duncan, Ruth, and Klok, Harm-Anton
- Subjects
Pharmacology ,Design ,coiled coil ,polymer-drug conjugates ,synthesis ,Copolymers ,Proteins ,reversible addition fragmentation chain transfer ,Therapeutics ,poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) ,Methotrexate ,Enzymatically Degradable Bonds ,Peptide ,peptides ,Specificity ,Stability - Abstract
This paper reports on the cell uptake and trafficking properties of a series of non-covalent polymer-drug conjugates. These nanomedicines are composed of a poly(N-(2-hydroxypropyl)methacrylamide) backbone functionalized with multiple copies of a drug. The drug moieties are attached to the polymer via a non-covalent, so called coiled coil motif, which is formed by heterodimerization of two complementary peptide strands, one of which is attached to the polymer carrier and the other to the drug. Cytotoxicity and FACS experiments, which were carried out with model anticancer drug or fluorophore conjugates, provided insight into the cell uptake and trafficking behavior of these conjugates.