PL3 CendR peptide shows specific uptake in cultured Y79 retinoblastoma cells with nucleolar accumulation

IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY European Journal of Pharmaceutical Sciences Pub Date : 2024-07-25 DOI:10.1016/j.ejps.2024.106866
Sonja Korhonen , Stef Bosch , Antero Erkinheimo , Tatu Lajunen , Kirsi Rilla , Tambet Teesalu , Astrid Subrizi , Marika Ruponen , Arto Urtti , Mika Reinisalo
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Abstract

Retinoblastoma is the most common pediatric intraocular malignant tumor affecting 1:15 000–1:20 000 live births. Even though the survival rate in developed countries is over 90 %, more efficient treatment options are needed for better vision salvage and reduction of the adverse effects. Therefore, we investigated fluorescein-labeled PL3 peptide targeting properties towards the Y79 retinoblastoma cell line in vitro. Through the application of cellular imaging and flow cytometry techniques, the PL3 peptide exhibited a rapid and specific internalization within Y79 cells, with subsequent translocation to the cell nuclei, showcasing notable accumulation in the nucleoli. This phenomenon was not present in other investigated cell lines and was not observable with similarly charged and length control peptide. However, the exact mechanism behind this Y79 cell line-specific nuclear and nucleolar targeting pattern remains elusive. In the future, this targeting process could facilitate specific treatment modalities of retinoblastoma with PL3 peptide-coupled drug delivery technologies.

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PL3 CendR 肽在培养的 Y79 视网膜母细胞瘤细胞中显示出特异性摄取,并伴有核小体聚集。
视网膜母细胞瘤是最常见的小儿眼内恶性肿瘤,发病率为 1:15 000-1:20 000。尽管发达国家的存活率超过 90%,但仍需要更有效的治疗方案来挽救视力和减少不良反应。因此,我们在体外研究了荧光素标记的 PL3 肽对 Y79 视网膜母细胞瘤细胞系的靶向特性。通过应用细胞成像和流式细胞术技术,PL3 肽在 Y79 细胞内表现出快速和特异性的内化,随后转位到细胞核,并在核小体中显著聚集。这种现象在其他被研究的细胞系中并不存在,带类似电荷和长度的对照肽也无法观察到。然而,Y79 细胞系特异性的细胞核和核小体靶向模式背后的确切机制仍不清楚。未来,这种靶向过程将有助于利用PL3肽耦合给药技术对视网膜母细胞瘤进行特定治疗。
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来源期刊
CiteScore
9.60
自引率
2.20%
发文量
248
审稿时长
50 days
期刊介绍: The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.
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