Daunomycin Nanocarriers with High Therapeutic Payload for the Treatment of Childhood Leukemia.

IF 5.5 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Rosa M Giráldez-Pérez, Elia M Grueso, Antonio J Montero-Hidalgo, Cristina Muriana-Fernández, Edyta Kuliszewska, Raúl M Luque, Rafael Prado-Gotor
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Abstract

Background/Objectives: Malignant neoplasms in children include leukemias. The main types are B-cell acute lymphoblastic leukemia (B-ALL) and acute myeloid leukemia (AML). Treatments are expensive, which is a particular problem in low-income countries. The main objective of this work was to develop specific nanosystems with small amounts of drug, allowing for affordable treatments. To this end, we designed ternary gold nanosystems (Au@16-Ph-16/DNA-Dauno) composed of daunomycin, a DNA biopolymer as a stabilizer, and the cationic surfactant gemini (TG) as a compacting agent for the DNA-daunomycin complex. Methods: Fluorescence, UV-visible, and CD spectroscopy, DLS and zeta potential, cell viability assays, TEM, AFM, and confocal microscopy were used to characterize and optimize nanocomposites. Results: The nanoparticles (Au@TG) obtained were small, stable, and highly charged in solution, allowing for optimal absorption and efficacy, capable of inducing the aggregation of the ternary nanosystem upon entering the cell, further enhancing its anticancer effect. Using nanoparticles, treatments can be redirected to the site of action, increasing the solubility and stability of the drug, minimizing the side effects of traditional treatments, and helping to overcome resistance to chemotherapy Conclusions: A significant decrease in the growth of pediatric B-ALL-derived cell lines (SEM and SUP-B15), constituting a potential and more affordable therapy for this type of pathology.

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高有效载荷纳米载体治疗儿童白血病的研究。
背景/目的:儿童恶性肿瘤包括白血病。主要类型有b细胞急性淋巴细胞白血病(B-ALL)和急性髓性白血病(AML)。治疗费用昂贵,这在低收入国家是一个特别的问题。这项工作的主要目标是开发具有少量药物的特定纳米系统,从而允许负担得起的治疗。为此,我们设计了三元金纳米系统(Au@16-Ph-16/DNA- dauno),该系统由DNA生物聚合物道诺霉素作为稳定剂,阳离子表面活性剂gemini (TG)作为DNA-道诺霉素复合物的密密剂组成。方法:采用荧光、紫外可见、CD光谱、DLS和zeta电位、细胞活力测定、TEM、AFM和共聚焦显微镜对纳米复合材料进行表征和优化。结果:获得的纳米颗粒(Au@TG)体积小、稳定性好,在溶液中电荷高,具有最佳的吸收和功效,能在进入细胞后诱导三元纳米体系聚集,进一步增强其抗癌作用。使用纳米颗粒,治疗可以重定向到作用部位,增加药物的溶解度和稳定性,最大限度地减少传统治疗方法的副作用,并有助于克服化疗耐药性。结论:儿童b - all来源的细胞系(SEM和SUP-B15)的生长显著减少,为这类病理提供了一种潜在的、更经济的治疗方法。
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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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