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Turkish Journal of Biology

Abstract

Breast cancer is the most common cancer type and the major cause of death in females worldwide. For effective breast cancer treatment, systems with promising delivery of anticancer agents is an important strategy. Peptide 18 (P18), a tumor homing peptide, shows high binding affinity towards breast cancer cells. Nanoliposomes are known to have enhanced accumulation ability in tumors with longer systemic circulation. Poly (2-ethyl-2-oxazoline) (PEtOx) polymers conjugated with DOPE were used to prepare PEtOx-DOPE nanoliposomes. BikDD is a mutant form of Bik gene, a member of the BH3-only proapoptotic genes, mimics the constitutively phosphorylated form of the gene. To the best of our knowledge, this study presents a novel approach by investigating P18-conjugated PEtOX-DOPE nanoliposomes (P18-PEtOx-DOPE) for the targeted delivery of the BikDD gene to the AU565 breast cancer model. Site-directed mutated BikDD gene was loaded into P18-PEtOx-DOPE nanoliposome and then the targeted drug delivery system was assessed in vitro and in vivo breast cancer models for efficiency, safety and efficacy. The increased Bik mRNA expression levels in AU565 cells suggest high effectiveness of the targeting PEtOx-DOPE nanoliposomes. Following in vitro studies, the delivery of BikDD gene by P18-PEtOx-DOPE nanoliposomes were analyzed in CD-1 nude mice models. The animal study showed no significant difference in tumor volume of CD-1 nude mice treated with P18-PEtOx-DOPE-BikDD nanoliposomes when compared to the free delivery of BikDD gene. Our preclinical studies suggest that P18-PEtOx-DOPE-BikDD nanoliposomes may be promising gene carriers used in targeted breast cancer therapy. Thus, further studies should be carried out to determine the prolonged usage of this drug delivery system in breast cancer therapy.

Author ORCID Identifier

ZEYNEP BOLAT: 0000-0002-9216-6336

AYÇA NEZİR: 0000-0001-8229-1865

ONGUN SAKA: 0000-0002-8726-6391

ITIR ZEMHERİ: 0000-0003-0247-0332

SEVGİ GÜLYÜZ: 0000-0002-2576-3085

UMUT ÖZKÖSE: 0000-0003-4807-6322

ÖZGÜR YILMAZ: 0000-0003-3892-2775

ASUMAN BOZKIR: 0000-0002-2782-3280

DİLEK TELCİ: 0000-0002-2793-6533

FİKRETTİN ŞAHİN: 0000-0003-1503-5567

DOI

10.55730/1300-0152.2706

Keywords

Breast cancer, BikDD gene, Targeted therapy, Gene delivery, Nanoliposomes

First Page

299

Last Page

307

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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