Prostate cancer cell-specific BikDDA delivery by targeted polymersomes
- PDF / 1,994,978 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 24 Downloads / 176 Views
ORIGINAL ARTICLE
Prostate cancer cell‑specific BikDDA delivery by targeted polymersomes Umut Can Oz1,2 · Zeynep Busra Bolat3 · Alessandro Poma2 · Lijuan Guan2 · Dilek Telci3 · Fikrettin Sahin3 · Giuseppe Battaglia2,4,5 · Asuman Bozkır1 Received: 7 January 2020 / Accepted: 11 February 2020 © King Abdulaziz City for Science and Technology 2020
Abstract 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(OEG10MA)20-PDPA100) 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(OEG10MA)20-PDPA100 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(OEG10MA)20-PDPA100 copolymer or attaching a maleimide-modified targeting peptide onto a thiol-terminated P(OEG10MA)20-PDPA100 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. Keywords Polymersomes · BikDDA · Gene delivery · Non-viral vector · Prostate cancer
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13204-020-01287-0) contains supplementary material, which is available to authorized users. * Giuseppe Battaglia [email protected] * Asuman Bozkır [email protected] 1
Department of Pharmaceutical Technology, Faculty of Pharmacy, Ankara University, 06560 Ankara, Turkey
2
Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK
3
Department of Genetics and Bioengineering, Yeditepe University, 34755 Istanbul, Turkey
4
Catalan Institution for Research and Advanced Studies, ICREA, Barcelona 08010, Spain
5
Institute of Physics of Living Systems, University College London, London, UK
Prostate cancer is the second most common type of cancer amongst men, with 1.1 million cases recorded worldwide (International Agency for Research on Cancer 2012). Depending on the patient’s condition, the treatment of
Data Loading...
