Application of Gold Nanoparticles for Improvement of Electroporation-Assisted Drug Delivery and Bleomycin Electrochemotherapy.

IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Barbora Lekešytė, Eglė Mickevičiūtė, Paulina Malakauskaitė, Anna Szewczyk, Eivina Radzevičiūtė-Valčiukė, Veronika Malyško-Ptašinskė, Augustinas Želvys, Natalija German, Almira Ramanavičienė, Julita Kulbacka, Jurij Novickij, Vitalij Novickij
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引用次数: 0

Abstract

Background/Objectives: Electrochemotherapy (ECT) is a safe and efficient method of targeted drug delivery using pulsed electric fields (PEF), one that is based on the phenomenon of electroporation. However, the problems of electric field homogeneity within a tumor can cause a diminishing of the treatment efficacy, resulting only in partial response to the procedure. This work used gold nano-particles for electric field amplification, introducing the capability to improve available elec-trochemotherapy methods and solve problems associated with field non-homogeneity. Methods: We characterized the potential use of gold nanoparticles of 13 nm diameter (AuNPs: 13 nm) in combination with microsecond (0.6-1.5 kV/cm × 100 μs × 8 (1 Hz)) and nanosecond (6 kV/cm × 300-700 ns × 100 (1, 10, 100 kHz and 1 MHz)) electric field pulses. Finally, we tested the most prominent protocols (microsecond and nanosecond) in the context of bleomycin-based electrochemotherapy (4T1 mammary cancer cell line). Results: In the nano-pulse range, the synergistic effects (improved permeabilization and electrotransfer) were profound, with increased pulse burst frequency. Addi-tionally, AuNPs not only reduced the permeabilization thresholds but also affected pore resealing. It was shown that a saturated cytotoxic response with AuNPs can be triggered at significantly lower electric fields and that the AuNPs themselves are non-toxic for the cells either separately or in combination with bleomycin. Conclusions: The used electric fields are considered sub-threshold and/or not applicable for electrochemotherapy, however, when combined with AuNPs results in successful ECT, indicating the methodology's prospective applicability as an anticancer treatment method.

应用金纳米粒子改进电穿孔辅助给药和博莱霉素电化学疗法
背景/目的:电化学疗法(ECT)是一种利用脉冲电场(PEF)进行靶向给药的安全有效的方法,它以电穿孔现象为基础。然而,肿瘤内的电场均匀性问题会导致疗效降低,从而使治疗过程仅产生部分反应。这项研究利用金纳米粒子进行电场放大,从而改进了现有的电化学疗法方法,并解决了电场不均匀性带来的问题。方法我们研究了直径为 13 nm 的金纳米粒子(AuNPs:13 nm)与微秒(0.6-1.5 kV/cm × 100 μs × 8 (1 Hz))和纳秒(6 kV/cm × 300-700 ns × 100 (1, 10, 100 kHz and 1 MHz))电场脉冲结合使用的潜力。最后,我们在基于博莱霉素的电化学疗法(4T1 乳腺癌细胞系)中测试了最主要的方案(微秒和纳秒)。测试结果在纳秒脉冲范围内,随着脉冲爆发频率的增加,协同效应(改善通透性和电转移)非常显著。此外,AuNPs 不仅降低了通透阈值,还影响了孔隙的再封闭。研究表明,使用 AuNPs 可以在明显较低的电场下触发饱和细胞毒性反应,而且 AuNPs 本身无论是单独使用还是与博莱霉素一起使用都不会对细胞产生毒性。结论所使用的电场被认为是亚阈值电场和/或不适用于电化学疗法,然而,当与 AuNPs 结合使用时,则可成功实现 ECT,这表明该方法有望成为一种抗癌治疗方法。
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来源期刊
Pharmaceutics
Pharmaceutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
7.90
自引率
11.10%
发文量
2379
审稿时长
16.41 days
期刊介绍: Pharmaceutics (ISSN 1999-4923) is an open access journal which provides an advanced forum for the science and technology of pharmaceutics and biopharmaceutics. It publishes reviews, regular research papers, communications,  and short notes. Covered topics include pharmacokinetics, toxicokinetics, pharmacodynamics, pharmacogenetics and pharmacogenomics, and pharmaceutical formulation. Our aim is to encourage scientists to publish their experimental and theoretical details in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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