Starlike vs. classic macromolecular prodrugs: two different antibody-targeted HPMA copolymers of doxorubicin studied in vitro and in vivo as potential anticancer drugs
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu srovnávací studie, časopisecké články, práce podpořená grantem
PubMed
14620507
DOI
10.1023/a:1026170830782
Knihovny.cz E-zdroje
- 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
- protinádorová antibiotika chemie farmakokinetika 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
- doxorubicin MeSH
- hydroxypropyl methacrylate MeSH Prohlížeč
- methakryláty MeSH
- monoklonální protilátky MeSH
- prekurzory léčiv MeSH
- protinádorová antibiotika MeSH
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.
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