Delivery of doxorubicin loaded P18 conjugated-poly (2-ethyl-oxazoline)-DOPE nanoliposomes for targeted therapy of breast cancer

Bolat Z. B., Nezir A. E., DEVRİM GÖKBERK B., Zemheri E., Gulyuz S., Ozkose U. U., ...Daha Fazla

TOXICOLOGY AND APPLIED PHARMACOLOGY, cilt.428, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 428
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1016/j.taap.2021.115671
  • Dergi Adı: TOXICOLOGY AND APPLIED PHARMACOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: Breast cancer, Doxorubicin, Drug Delivery, Nanoliposomes, Peptide 18, Targeted therapy, TUMOR-CELL LINES, DRUG-DELIVERY, POLYMERIC NANOPARTICLES, LIPOSOMAL DOXORUBICIN, CARDIOTOXICITY, MICELLES, PROFILE, GROWTH
  • Ankara Üniversitesi Adresli: Evet

Özet

Breast cancer, a heterogeneous disease, has the highest incidence rate and is a major cause of death in females worldwide. Drug delivery by using nanotechnology has shown great promise for improving cancer treatment. Nanoliposomes are known to have enhanced accumulation ability in tumors due to prolonged systemic circulation. Peptide 18 (P18), a tumor homing peptide targeting keratin-1 (KRT-1), was previously shown to have high binding affinity towards breast cancer cells. In this study, we investigate the ability of P18 conjugated PEtOxDOPE nanoliposomes (P18-PEtOx-DOPE) for the targeted delivery of doxorubicin to AU565 breast cancer model. Toxicology studies of PEtOx-DOPE nanoliposomes performed on normal breast epithelial cells (MCF10A), showed minimal toxicity. Doxorubicin delivery by P18-PEtOx-DOPE to AU565 cells induces cytotoxicity in a dose and time dependent manner causing mitotic arrest in G2/M phase at 24 h. Anti-cancer activity of P18-PEtOxDOPE-DOX nanoliposomes on AU565 cells was detected by Annexin V/PI apoptosis assay. In terms of in vivo antitumor efficacy, P18-PEtOx-DOPE-DOX nanoliposomes administration to AU565 CD-1 nu/nu mice model showed significant decrease in tumor volume suggesting that DOX delivered by these nanoliposomes elicited a strong antitumor response comparable to the free delivery of doxorubicin. Overall, our results offered preclinical proof for the use of P18-PEtOx-DOPE-DOX nanoliposomes in KRT-1+ breast cancer therapy.