Targeted delivery of elesclomol using a magnetic mesoporous platform improves prostate cancer treatment both in vitro and in vivo.

Autor: Tarin M; Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran., Babaei M; Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran., Eshghi H; Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran., Matin MM; Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran; Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran. Electronic address: matin@um.ac.ir., Saljooghi AS; Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran; Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran. Electronic address: saljooghi@um.ac.ir.
Jazyk: angličtina
Zdroj: Talanta [Talanta] 2024 Apr 01; Vol. 270, pp. 125539. Date of Electronic Publication: 2023 Dec 11.
DOI: 10.1016/j.talanta.2023.125539
Abstrakt: Background: To improve the anticancer properties of elesclomol (ELC), targeted theranostic nanoparticles (NPs; APT-PEG-Au-MMNPs@ELC) were designed to increase the selectivity of the drug delivery system (DDS).
Materials and Methods: ELC was synthesized and entrapped in the open porous structure of magnetic mesoporous silica nanoparticles (MMNPs). The pore entrance of MMNPs was then blocked using gold gatekeepers. Finally, the external surfaces of the particles were grafted with functional polyethylene glycol (PEG) and EpCAM aptamer to generate biocompatible and targeted NPs. In the next step, the physicochemical properties of prepared NPs were fully evaluated and their anticancer potential was evaluated both in vitro and in vivo.
Results: The targeted NPs were successfully synthesized with a final size diameter of 81.13 ± 7.41 nm. The results indicated a pH-dependent release pattern, which sustained for 72 h despite an initial rapid release. Upon exposure to APT-PEG-Au-MMNPs@ELC, higher cytotoxicity was observed in human prostate cancer cells (PC-3) as compared with control Chinese hamster ovary (CHO) cells, indicating higher specificity of targeted NPs against EpCAM-positive cancerous cells. Moreover, APT-PEG-Au-MMNPs@ELC could induce apoptosis in PC-3 cells. In vivo results on a PC-3 xenograft tumor model demonstrated that targeted NPs could significantly inhibit tumor growth and diminish severe side effects of ELC, compared to the free drug.
Conclusion: Collectively, APT-PEG-Au-MMNPs@ELC could be considered a promising theranostic platform for the targeted delivery of ELC to improve its therapeutic effects in prostate cancer.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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