Polymeric anticancer drugs with pH-controlled activation.
The paper is dealing with the synthesis and properties of new, nontargeted or antibody-targeted pH-sensitive polymer-doxorubicin (DOX) conjugates designed as anticancer drugs facilitating site-specific therapy. These conjugates are stable and inactive during transport in the body but activate inside target cells as a result of pH changes outside and inside the cells. Cytotoxicity of the conjugates depends on the detailed structure of the polymer and of the spacer between the drug and polymer carrier. In both protective and therapeutic regimes of drug administration, the in vivo antitumor activity of the pH-sensitive conjugates containing DOX was significantly enhanced (T-cell lymphoma EL 4, C57BL/16 mice) in comparison with the free DOX or classic PK1, the PHPMA-DOX conjugate clinically tested at present.
Ulbrich
K
K
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovský Sq. 2, 162 06 Prague 6, Czech Republic. ulbrich@imc.cas.cz
Etrych
T
T
Chytil
P
P
Pechar
M
M
Jelinkova
M
M
Rihova
B
B
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016399:Lymphoma, T-Cell / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011108:Polymers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000970:Antineoplastic Agents; D011108:Polymers; D011109:Polymethacrylic Acids; C055176:doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate; D004317:Doxorubicin