Folic Acid-Conjugated pH and Redox-Sensitive Ellipsoidal Hybrid Magnetic Nanoparticles for Dual-Triggered Drug Release


Birlik Demirel G., Aygul E., DAĞ A. , ATASOY S. , Cimen Z., Cetin B.

ACS Applied Bio Materials, cilt.3, sa.8, ss.4949-4961, 2020 (Diğer Kurumların Hakemli Dergileri) identifier

  • Cilt numarası: 3 Konu: 8
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1021/acsabm.0c00488
  • Dergi Adı: ACS Applied Bio Materials
  • Sayfa Sayıları: ss.4949-4961

Özet

© 2020 American Chemical Society.Stimuli-sensitive and multifunctional nanoparticles are highly desirable biomedical materials for triggered and targeted drug delivery applications. Here, we have designed pH- A nd redox-triggered magnetic lipid-polymer hybrid nanoparticles (MHNPs) with a core-shell structure. This design is composed of a silica-/mesoporous silica-coated ellipsoidal magnetic nanoparticle with multifunctionality: Carrying the anticancer drug (doxorubicin, DOX), the cancer cell targeting ligand (folic acid-conjugated poly(ethylene glycol), FA-PEG) polymer, and being coated with a biocompatible pH-/redox-responsive (poly-l-histidine-poly(ethylene glycol)-lipoic acid; PLH-PEG-LA) polymer. The lipoic acid units of the PLH-PEG-LA shell of the FA-MHNPs were cross-linked using 1,4-dithiothreitol (DTT). When the FA-MHNPs-DOX were exposed to an endolysosomal pH of 5.5 and 10 mM glutathione (GSH), the particles exhibited a very efficient DOX release profile within 24 h. In addition, cytotoxicity, uptake, and apoptosis assays were performed against breast cancer cell lines. These results showed that FA-MHNPs-DOX promote an enhanced uptake and cell morbidity compared to the nontargeted MHNPs-DOX against tested cell lines. Moreover, the FA-MHNPs-DOX exhibited very effective cytotoxicity and also decreased the cell viability through apoptosis against breast cancer cell lines. In conclusion, it can be said that the pH and redox dual-responsive hybrid FA-MHNPs-DOX has a great potential for controlled drug release.