Prostate cancer cell-specific BikDDA delivery by targeted polymersomes

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Öz U. C., Bolat Z. B., Poma A., Guan L., Telci D., Şahin F., ...Daha Fazla

APPLIED NANOSCIENCE, cilt.10, sa.9, ss.3389-3401, 2020 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 10 Sayı: 9
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1007/s13204-020-01287-0
  • Dergi Adı: APPLIED NANOSCIENCE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.3389-3401
  • Anahtar Kelimeler: Polymersomes, BikDDA, Gene delivery, Non-viral vector, Prostate cancer, LOADED POLYMERSOMES, ENCAPSULATION, TUMOR, EXPRESSION, PACLITAXEL, PEPTIDES, VESICLES, DESIGN, DNA
  • Ankara Üniversitesi Adresli: Evet

Özet

In this paper, we report the polymersome-mediated intracellular delivery of pro-apoptotic BikDDA gene using two different peptide-copolymer covalent conjugation strategies specific for prostate cancer targeting. The BikDDA gene was used as a therapeutic agent on prostate cancer cells. The transfection efficiency of BikDDA-loaded poly[oligo(ethyleneglycol) methacrylate]-co-poly[2-(diisopropylamino) ethyl methacrylate] (P(OEG(10)MA)(20)-PDPA(100)) polymersomes revealed that they could serve as a suitable non-viral gene transfection tool. The targeted delivery of BikDDA into prostate cancer cells (LNCaP) using polymersomes was successfully carried out by conjugating the PSMA-targeting moiety (peptide 563) to P(OEG(10)MA)(20)-PDPA(100)copolymer using either succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC) as a bifunctional linker between the thiol-bearing targeting peptide and amino-bearing P(OEG(10)MA)(20)-PDPA(100)copolymer or attaching a maleimide-modified targeting peptide onto a thiol-terminated P(OEG(10)MA)(20)-PDPA(100)copolymer. The pH-responsive and biocompatible polymersomes, conjugated with peptide 563, exhibited an enhanced cellular uptake by LNCaP cells in comparison to the healthy prostate epithelial cell line PNT1A, thus indicating the cell-specific delivery. The increased Bik mRNA expression and cell death in these LNCaP cells indicates high effectiveness of the targeting polymersomes. According to these results, we believe more efficient gene delivery systems via specifically targeted pH-sensitive polymersomes can be a promising approach and promote the development of novel therapies against prostate cancer.