Assessment of the Toxicity of Free and PLGA-Encapsulated Phospholipase A2 CB: An In Vitro Approach.

IF 3.5 4区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current medicinal chemistry Pub Date : 2025-04-10 DOI:10.2174/0109298673274499250327053516

Vanessa Barbosa Pinheiro Gonçalves, Gabriel Acácio de Moura, João Pedro Viana Rodrigues, Javier Martinez Latorre, Vicente Candela-Nogueira, Paula M Soriano-Teruel, Alba García-Fernández, Ramón Martínez Máñez, Marlos de Medeiros Chaves, Claudia do Ó Pessoa, Anderson Maciel de Lima, Andreimar Martins Soares, Roberto Nicolete

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引用次数: 0

Abstract

Background: The use of bioactive molecules isolated from rattlesnake venom and other poisons has been ongoing for years. Among these bioactive compounds present in snake venom, crotoxin (CTX) stands out as a β-heterodimeric neurotoxin isolated from the venom of Crotalus durissus terrificus. Research on this toxin for its applicability to tumor inhibition has advanced to clinical trials in recent years. Consequently, concerns regarding the use of a toxin as a treatment and the search for dose control that does not trigger extreme toxicity have emerged. Thus, it is necessary to investigate alternatives for controlled delivery and targeted toxin administration.

Method: This study aimed to evaluate the in vitro toxic action of CTX and its phospholipase A2 CB (PLA2CB) component, both free and encapsulated in polymeric nanoparticles. The inhibitory concentration value of 50% tumor growth (IC50) for CTX and PLA2CB was determined in an initial screening against six tumor cell lines. After identifying the lowest inhibitory concentration value of 0.8 μM observed in human melanoma (SK-MEL-103), this cell line was chosen.

Results: The cell death mechanism triggered by CTX and PLA2CB exhibited characteristics associated with the necrotic process. However, polymeric nanoparticles containing PLA2CB (NP-PLA2CB) demonstrated apoptosis-like cell death processes in flow cytometry. PLGA polymeric nanoparticles containing PLA2CB were synthesized using microfluidics, resulting in NP-PLA2CB with a diameter of 91 ± 2.9 nm and a zeta potential of -21.8 ± 3.2 mV. The encapsulation efficiency of PLA2CB was approximately 70% (protein content).

Conclusion: It was concluded that using the phospholipase component of the toxin in a polymeric-controlled delivery and targeted system may be an alternative solution to the issues in advancing this bioactive molecule in clinical-oncological studies. However, further studies are still being conducted for targeted treatment involving this nanotechnological approach.

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游离和plga包封的磷脂酶A2 CB的体外毒性评价。

背景：从响尾蛇毒液和其他毒物中分离出的生物活性分子的使用已经进行了多年。在这些存在于蛇毒中的生物活性化合物中，响尾蛇毒素（Crotalus durissus terrificus）是一种从响尾蛇毒液中分离出来的β-异二聚体神经毒素。近年来，对该毒素肿瘤抑制作用的研究已进入临床试验阶段。因此，人们开始关注使用某种毒素作为一种治疗方法，以及寻求不引发极端毒性的剂量控制。因此，有必要研究控制递送和靶向给药的替代方法。方法：本研究旨在评价CTX及其磷脂酶A2CB （PLA2CB）组分（游离和包封于聚合物纳米颗粒中）的体外毒性作用。初步筛选CTX和PLA2CB对6种肿瘤细胞系的50%肿瘤生长抑制浓度值（IC50）。在人类黑色素瘤（SK-MEL-103）中观察到的最低抑制浓度值为0.8 μM后，选择了该细胞系。结果：CTX和PLA2CB触发的细胞死亡机制表现出与坏死过程相关的特征。然而，含有PLA2CB的聚合纳米颗粒（NP-PLA2CB）在流式细胞术中显示出凋亡样细胞死亡过程。采用微流控技术合成了含有PLA2CB的PLGA聚合物纳米颗粒，得到了直径为91±2.9 nm， ζ电位为-21.8±3.2 mV的NP-PLA2CB。PLA2CB的包封率约为70%（蛋白质含量）。结论：利用毒素的磷脂酶组分在聚合物控制的递送和靶向系统中可能是在临床肿瘤研究中推进该生物活性分子问题的另一种解决方案。然而，涉及这种纳米技术方法的靶向治疗的进一步研究仍在进行中。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current medicinal chemistry 医学-生化与分子生物学

CiteScore

8.60

自引率

2.40%

发文量

468

审稿时长

3 months

期刊介绍： Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.