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Prostate cancer cell-specific BikDDA delivery by targeted polymersomes

Oz, UC; Bolat, ZB; Poma, A; Guan, L; Telci, D; Sahin, F; Battaglia, G; (2020) Prostate cancer cell-specific BikDDA delivery by targeted polymersomes. Applied Nanoscience , 10 pp. 3389-3401. 10.1007/s13204-020-01287-0. Green open access

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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.

Type: Article
Title: Prostate cancer cell-specific BikDDA delivery by targeted polymersomes
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s13204-020-01287-0
Publisher version: https://doi.org/10.1007/s13204-020-01287-0
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Polymersomes, BikDDA, Gene delivery, Non-viral vector, Prostate cancer
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Eastman Dental Institute
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/10100654
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