Recently hydrophilic poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) was used for BS-RNase modification to prevent its degradation in bloodstream or fast elimination. Polymer-conjugated BS-RNase preparations proved to be cytotoxic after intravenous or intraperitoneal application, whereas native BS-RNase was ineffective. Here RNase A unimer was conjugated with two HPMA polymers (classic and star) and their antitumor effects both in vitro and in vivo were compared with those of BS-RNase polymers. Surprisingly, the antitumor effect of RNase A conjugates was also pronounced. The RNase A conjugates (classic and star) injected intravenously to mice bearing melanoma tumor caused a significant reduction in tumor volume following ten doses of 5 and 1 mg/kg, respectively. Despite the antitumor activity observed in vivo, the in vitro tested cytotoxic activity of RNase A did not differ from that caused by native RNase A while native BS-RNase (50 microg/ml) totally inhibited DNA synthesis in treated cells. The experiments with 125I-labeled preparations demonstrated concentration-dependent internalization of native BS-RNase by tumor cells within an hour, whereas the polymer conjugate (S-BS) was not internalized. On the contrary, the in vivo experiments showed that whereas 40% of S-BS conjugate persisted in bloodstream for 24h after administration, 98% of the native BS-RNase was already eliminated. Improved antitumor activities of PHPMA-modified RNases in vivo might be ascribed to their prolonged retention in bloodstream, better proteolytic stability and resistance to the action of the ribonuclease inhibitor.
- MeSH
- endoribonukleasy aplikace a dávkování chemie terapeutické užití MeSH
- injekce intraperitoneální MeSH
- injekce intravenózní MeSH
- konformace proteinů MeSH
- kyseliny polymethakrylové aplikace a dávkování chemie MeSH
- lidé MeSH
- lymfocyty metabolismus MeSH
- melanom experimentální farmakoterapie patologie MeSH
- molekulární struktura MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buňky kultivované metabolismus MeSH
- nosiče léků MeSH
- pankreatická ribonukleasa aplikace a dávkování chemie terapeutické užití MeSH
- protinádorové látky aplikace a dávkování chemie terapeutické užití MeSH
- radioizotopy jodu MeSH
- skot MeSH
- vazebná místa fyziologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- xenogenní modely - testy protinádorové aktivity MeSH
- způsoby aplikace léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- skot MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- Duxon MeSH Prohlížeč
- endoribonukleasy MeSH
- kyseliny polymethakrylové MeSH
- nosiče léků MeSH
- pankreatická ribonukleasa MeSH
- protinádorové látky MeSH
- radioizotopy jodu MeSH
- ribonuclease SPL MeSH Prohlížeč
