We designed and synthesized a new delivery system for the anticancer drug doxorubicin based on a biocompatible hydrophilic poly(2-ethyl-2-oxazoline) (PEtOx) carrier with linear architecture and narrow molar mass distribution. The drug is connected to the polymer backbone via an acid-sensitive hydrazone linker, which allows its triggered release in the tumor. The in vitro studies demonstrate successful cellular uptake of conjugates followed by release of the cytostatic cargo. In vivo experiments in EL4 lymphoma bearing mice revealed prolonged blood circulation, increased tumor accumulation and enhanced antitumor efficacy of the PEtOx conjugate having higher molecular weight (40 kDa) compared to the lower molecular weight (20 kDa) polymer. Finally, the in vitro and in vivo anti-cancer properties of the prepared PEtOx conjugates were critically compared with those of the analogous system based on the well-established PHPMA carrier. Despite the relatively slower intracellular uptake of PEtOx conjugates, resulting also in their lower cytotoxicity, there are no substantial differences in in vivo biodistribution and anti-cancer efficacy of both classes of polymer-Dox conjugates. Considering the synthetic advantages of poly(2-alkyl-2-oxazoline)s, the presented study demonstrates their potential as a versatile alternative to well-known PEO- or PHPMA-based materials for construction of drug delivery systems.

• Klíčová slova
• Doxorubicin, Drug delivery, Hydrazone bond, Nanomedicine, Poly(2-oxazoline),
• MeSH
• akrylamidy chemie   MeSH
• doxorubicin chemie   terapeutické užití   MeSH
• HeLa buňky MeSH
• konfokální mikroskopie MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nanomedicína metody   MeSH
• nosiče léků chemie   MeSH
• polyaminy chemie   MeSH
• polymery chemie   MeSH
• průtoková cytometrie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• akrylamidy MeSH
• doxorubicin MeSH
• N-(2-hydroxypropyl)methacrylamide MeSH Prohlížeč
• nosiče léků MeSH
• poly(2-ethyl-2-oxazoline) MeSH Prohlížeč
• polyaminy MeSH
• polymery MeSH

Poly(2-alkyl-2-oxazoline)s are biocompatible polymers with polypeptide-isomeric structures that are attracting increasing interest as biomaterials for drug, gene, protein, and radionuclide delivery. They are, however, still relatively new in comparison to other classes of hydrophilic water-soluble polymers already established for such use, including poly(ethylene oxide), polyvinylpyrrolidone, and polymethacrylamides such as poly[N-(2-hydroxypropyl)methacrylamide]. This feature article critically compares the synthetic aspects and physicochemical and biological properties of poly(2-alkyl-2-oxazoline)s and these commonly studied polymers in terms of their suitability for biomedical applications.

• MeSH
• biokompatibilní materiály chemie   MeSH
• hydrofobní a hydrofilní interakce MeSH
• nosiče léků chemie   MeSH
• oxazoly chemická syntéza   chemie   MeSH
• polymery chemie   MeSH
• roztoky chemie   MeSH
• voda chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biokompatibilní materiály MeSH
• nosiče léků MeSH
• oxazoly MeSH
• poly(2-oxazoline) MeSH Prohlížeč
• polymery MeSH
• roztoky MeSH
• voda MeSH