Optimizing Jasplakinolide delivery in rhabdomyosarcoma cells using pulsed electric fields (PEFs) for enhanced therapeutic impact

IF 4.5 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioelectrochemistry Pub Date : 2025-10-01 Epub Date: 2025-03-12 DOI:10.1016/j.bioelechem.2025.108969

Anna Szewczyk , Nina Rembiałkowska , Marta Migocka-Patrzałek , Wojciech Szlasa , Agnieszka Chwiłkowska , Małgorzata Daczewska , Vitalij Novickij , Julita Kulbacka

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Abstract

This study explores the combination of jasplakinolide with electroporation (JSP + EP), a method enhancing targeted molecule delivery. CHO-K1 (Chinese hamster ovarian), C2C12 (mouse myoblast), and RD (rhabdomyosarcoma) cells were treated with jasplakinolide (50 nM) in HEPES buffer and exposed to electrical pulses (0.8–1.2 kV/cm). Cell viability was measured via the MTS assay, cytoskeleton structure was assessed with confocal microscopy, and docking studies examined jasplakinolide-actin interactions. The combination of jasplakinolide and electric pulses synergistically affected RMS cells (Rhabdomyosarcoma), causing significant cytoskeletal changes and reduced viability. Docking studies revealed that jasplakinolide interacts with both monomeric and filamentous actin, highlighting a dual mechanism. Confocal imaging showed substantial actin cytoskeleton disruption in cancer cells, with minimal effects on normal cells. Jasplakinolide combined with electric pulses can specifically target cancer cells with less cytotoxicity to normal cells, potentially reducing side effects following the clinical procedure.

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利用脉冲电场（pef）优化Jasplakinolide在横纹肌肉瘤细胞中的传递，以增强治疗效果

本研究探讨了jasplinolide与电穿孔（JSP + EP）的结合，这是一种增强靶向分子递送的方法。将CHO-K1（中国仓鼠卵巢）、C2C12（小鼠成肌细胞）和RD（横纹肌肉瘤）细胞在HEPES缓冲液中用jasplakinolide （50 nM）处理，并暴露于0.8-1.2 kV/cm的电脉冲下。通过MTS法测定细胞活力，用共聚焦显微镜评估细胞骨架结构，对接研究检测茉莉烯内酯-肌动蛋白相互作用。jasplinolide和电脉冲的组合协同影响RMS细胞（横纹肌肉瘤），引起显著的细胞骨架变化和活力降低。对接研究表明，茉莉烯内酯与单体和丝状肌动蛋白相互作用，突出了双重机制。共聚焦成像显示癌细胞中肌动蛋白骨架的破坏，对正常细胞的影响很小。茉莉烯内酯结合电脉冲可以特异性靶向癌细胞，对正常细胞的细胞毒性较小，潜在地减少临床治疗后的副作用。

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来源期刊

Bioelectrochemistry 生物-电化学

CiteScore

9.10

自引率

6.00%

发文量

238

审稿时长

38 days

期刊介绍： An International Journal Devoted to Electrochemical Aspects of Biology and Biological Aspects of Electrochemistry Bioelectrochemistry is an international journal devoted to electrochemical principles in biology and biological aspects of electrochemistry. It publishes experimental and theoretical papers dealing with the electrochemical aspects of: • Electrified interfaces (electric double layers, adsorption, electron transfer, protein electrochemistry, basic principles of biosensors, biosensor interfaces and bio-nanosensor design and construction. • Electric and magnetic field effects (field-dependent processes, field interactions with molecules, intramolecular field effects, sensory systems for electric and magnetic fields, molecular and cellular mechanisms) • Bioenergetics and signal transduction (energy conversion, photosynthetic and visual membranes) • Biomembranes and model membranes (thermodynamics and mechanics, membrane transport, electroporation, fusion and insertion) • Electrochemical applications in medicine and biotechnology (drug delivery and gene transfer to cells and tissues, iontophoresis, skin electroporation, injury and repair). • Organization and use of arrays in-vitro and in-vivo, including as part of feedback control. • Electrochemical interrogation of biofilms as generated by microorganisms and tissue reaction associated with medical implants.