Polymer nanomedicines with anti-tumor activity should exhibit sufficient stability during systemic circulation to the target tissue; however, they should release the active drug selectively in the tumor. Thus, choice of a tumor-specific stimuli-sensitive spacer between the drug and the carrier is critical. Here, a series of polymer conjugates of anti-cancer drugs doxorubicin and pirarubicin covalently bound to copolymers based on N-(2-hydroxypropyl)methacrylamide via various enzymatically cleavable oligopeptide spacers were prepared and characterized. The highest rate of the drug release from the polymer carriers in presence of the lysosomal protease cathepsin B was determined for the copolymers with Val-Cit-Aba spacer. Copolymers containing pirarubicin were more cytotoxic and showed higher internalization rate than the corresponding doxorubicin counterparts. The conjugates containing GFLG and Val-Cit-Aba spacers exhibited the highest anti-tumor efficacy in vivo against murine sarcoma S-180, the highest rate of the enzymatically catalyzed drug release, and the highest cytotoxicity in vitro.

Faculty of Pharmaceutical Sciences Sojo University Ikeda 4 22 1 Nishi ku Kumamoto 860 0082 Japan

Institute of Macromolecular Chemistry Czech Academy of Sciences Heyrovského nám 2 162 06 Prague 6 Czech Republic

School of Pharmacy Queen's University Belfast 97 Lisburn Road Belfast BT9 7BL UK

References provided by Crossref.org

Polymer-Antimicrobial Peptide Constructs with Tailored Drug-Release Behavior