Nejvíce citovaný článek - PubMed ID 31098602
Unexpected therapeutic effects of cisplatin
Stimuli-responsive hyaluronic acid carriers face limitations due to limited carboxyl groups, which are divided between drug conjugation and functional modifications. Thermoresponsive nanogels based on selectively oxidized hyaluronan (2,3-dicarboxy hyaluronate, DCH) grafted with poly(N-isopropyl acrylamide) (pNIPAM) were developed for phenanthriplatin (PhPt) delivery. Sequential oxidation after pNIPAM grafting introduced additional carboxylic groups, enabling a more efficient drug loading and controlled release. Compared to nonoxidized pNIPAM-modified HA, this approach achieved 3 times higher loading efficacy and significantly slower drug release. Upon PhPt loading, DCH-pNIPAM conjugates self-assembled into nanogels, with the drug binding mode (ionic vs covalent) influencing particle rearrangement and drug release behavior. Covalently bound PhPt showed reduced release compared to nonthermoresponsive controls. In vitro studies on ovarian cancer cell lines, including cisplatin-resistant variants, demonstrated up to an 18-fold increase in cytotoxicity versus free PhPt. These nanogels offer a promising strategy for enhancing drug efficacy, reducing off-target effects, and overcoming resistance in cancer therapy.
- MeSH
- akrylové pryskyřice chemie MeSH
- chemorezistence * účinky léků MeSH
- cisplatina * farmakologie MeSH
- kyselina hyaluronová * chemie MeSH
- lékové transportní systémy MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory vaječníků * farmakoterapie patologie MeSH
- nanogely chemie MeSH
- nosiče léků chemie MeSH
- organoplatinové sloučeniny * farmakologie chemie aplikace a dávkování MeSH
- protinádorové látky * farmakologie chemie aplikace a dávkování MeSH
- uvolňování léčiv MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- akrylové pryskyřice MeSH
- cisplatina * MeSH
- kyselina hyaluronová * MeSH
- nanogely MeSH
- nosiče léků MeSH
- organoplatinové sloučeniny * MeSH
- poly-N-isopropylacrylamide MeSH Prohlížeč
- protinádorové látky * MeSH