PURPOSE: Two different monoclonal antibody-targeted HPMA copolymer-doxorubicin conjugates, classic and starlike, were synthesized to be used for site-specific cancer therapy. The anti-mouse Thy-1.2 (IgG3) and two anti-human CD71/A (IgG1) and CD71/B (IgG2a) monoclonal antibodies were used as targeting structures. METHODS: Their binding and cytotoxic activity in vitro, body distribution, and anticancer activity in vivo were evaluated. RESULTS: The results of flow cytometric analysis showed comparable binding of classic and starlike conjugates to the target cells. The in vitro cytotoxic effect was 10-fold higher if cancer cells were exposed to the starlike conjugate compared to the classic one. Biodistribution studies showed that the starlike conjugate remained in a relatively high concentration in blood, whereas the classic conjugate was found in a 6.5-times lower amount. In contrast to the low antitumor activity of free doxorubicin and nontargeted HPMA copolymer-doxorubicin conjugate, both anti-Thy-1.2 targeted conjugates (classic and starlike) cured all mice bearing T-cell lymphoma EL4. On the other hand, starlike conjugates containing anti-CD71/A or anti-CD71/B monoclonals as targeting structures were more effective against human colorectal cancer SW 620 than the classic one. CONCLUSIONS: We have shown that the starlike conjugates are more effective systems for targeted drug delivery and cancer treatment than classic conjugates.

• MeSH
• antibiotika antitumorózní chemie   farmakokinetika   farmakologie   MeSH
• buněčné dělení účinky léků   MeSH
• doxorubicin chemie   farmakokinetika   farmakologie   MeSH
• kolorektální nádory farmakoterapie   MeSH
• lidé MeSH
• lymfom T-buněčný farmakoterapie   MeSH
• methakryláty chemie   farmakologie   MeSH
• molekulární struktura MeSH
• monoklonální protilátky chemie   metabolismus   MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• prekurzory léčiv chemie   farmakologie   MeSH
• techniky in vitro MeSH
• tkáňová distribuce MeSH
• transplantace nádorů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• antibiotika antitumorózní MeSH
• doxorubicin MeSH
• hydroxypropyl methacrylate MeSH Prohlížeč
• methakryláty MeSH
• monoklonální protilátky MeSH
• prekurzory léčiv MeSH