Nuclear targeting peptide-modified, DOX-loaded, PHBV nanoparticles enhance drug efficacy by targeting to Saos-2 cell nuclear membranes

Sahin A., Eke G., Buyuksungur A., Hasirci N., HASIRCI V. N.

JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION, vol.29, no.5, pp.507-519, 2018 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 29 Issue: 5
  • Publication Date: 2018
  • Doi Number: 10.1080/09205063.2018.1423812
  • Journal Name: JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.507-519
  • Keywords: PHBV, biodegradable nanoparticles, nuclear drug delivery, doxorubicin, nuclear localization signal, PLGA NANOPARTICLES, POLY(LACTIDE-CO-GLYCOLIDE) NANOPARTICLES, DOXORUBICIN DELIVERY, CANCER-THERAPY, DISTINCT MODES, TUMOR-CELLS, APOPTOSIS, NANOTECHNOLOGY, MICRO/NANOPARTICLES, RELEASE
  • Middle East Technical University Affiliated: Yes

Abstract

The aim of this study was to target nano sized (266 +/- 25nm diameter) poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) particles carrying Doxorubicin (DOX), an anticancer agent, to human osteosarcoma cells (Saos-2). A nuclear targeting molecule (Nuclear Localization Signal, NLS), a 17 a.a. peptide, was attached onto the doxorubicin loaded nanoparticles. NLS conjugated nanoparticles surrounded the cell nuclei, but did not penetrate them. Free doxorubicinand doxorubicin loadednanoparticles entered the cytoplasm and were evenly distributed within the cytoplasm. The localization of the NLS-targetedparticles around the nuclear membrane caused a significantly higher decrease in the cancer cell numbers due to apoptosis or necrosis than the untargeted and free doxorubicin formulations showing the importance of targeting the nanoparticles to the nuclear membrane in the treatment of cancer.