Ávila-Ortega Alejandro, Villa-de la Torre Fabiola Elizabeth, Carrera-Figueiras Cristian, Martínez-Rizo Abril Bernardette, Talavera-Pech William Alejandro, Torres-Romero Julio César, Ceballos-Góngora Emanuel, García-Martínez Valeria, Pintor-Romero Valeria Guadalupe, Huchin-Chan Claribel, Vilchis-Nestor Alfredo Rafael, Arana-Argáez Víctor Ermilo
Cuerpo Académico de Química Fundamental y Aplicada, Facultad de Ingeniería Química, Universidad Autónoma de Yucatán, Mérida, Yucatán, México.
Laboratorio de Farmacología, Facultad de Química, Universidad Autónoma de Yucatán, Calle 43, No 613 X Calle 90, Col. Inalámbrica, CP. 97069, Mérida, Yucatán, México.
Naunyn Schmiedebergs Arch Pharmacol. 2025 May 14. doi: 10.1007/s00210-025-04244-2.
Chemotherapy drugs used in inflammatory disorders and some cancers, while effective, often cause diverse side toxic effects, prompting research into alternatives to ameliorate damage in healthy tissues. One strategy is to encapsulate doxorubicin (DOX) chemotherapeutic agents into nano-vehicles, such as organic-functionalized mesoporous nanoparticles, to reduce systemic leakage and adverse effects, such as inflammation. This study analyzes the toxicological and anti-inflammatory effects of a drug-delivered system (DDS) based on MCM-41 mesoporous silica nanoparticles modified with a pH-sensitive poly(β-amino ester) named MCM-41-PbAE. The effects of both blank nanoparticles (MCM-41-PbAE) and those with encapsulated DOX (MCM-41-PbAE-DOX) were evaluated in LPS-stimulated mouse macrophages and in an in vivo inflammation model. Characterization of nanoparticles was carried out through TEM, DLS, FTIR Z-potential, and thermogravimetric tests. Macrophages were treated with MCM-41-PbAE and MCM-41-PbAE-DOX particles at several concentrations, and the production of proinflammatory and anti-inflammatory cytokines, nitric oxide (NO), and hydrogen peroxide (HO) levels were determined. Toxicological evaluation was performed in BALB/c mice and the in vivo anti-inflammatory effect was evaluated in a carrageenan-induced paw edema model and the measuring serum levels of pro-inflammatory cytokines. Results indicated that MCM-41-PbAE-DOX significantly reduces NO and HO levels and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in dose-manner without affecting cell viability or causing toxicity in mice. Conversely, a reduction in carrageenan-induced paw edema and decreased levels of proinflammatory cytokines were noted, indicating the potential advantage of encapsulating DOX within MCM-41-PbAE nanoparticles, which could inhibit inflammation without compromising healthy cell viability.
用于炎症性疾病和某些癌症的化疗药物虽然有效，但常常会引起各种副作用，这促使人们研究替代方法以减轻对健康组织的损害。一种策略是将阿霉素（DOX）化疗药物封装到纳米载体中，如有机功能化介孔纳米颗粒，以减少全身渗漏和副作用，如炎症。本研究分析了一种基于用pH敏感的聚（β-氨基酯）修饰的MCM-41介孔二氧化硅纳米颗粒（称为MCM-41-PbAE）的药物递送系统（DDS）的毒理学和抗炎作用。在LPS刺激的小鼠巨噬细胞和体内炎症模型中评估了空白纳米颗粒（MCM-41-PbAE）和封装DOX的纳米颗粒（MCM-41-PbAE-DOX）的作用。通过透射电子显微镜（TEM）、动态光散射（DLS）、傅里叶变换红外光谱（FTIR）、Z电位和热重测试对纳米颗粒进行了表征。用几种浓度的MCM-41-PbAE和MCM-41-PbAE-DOX颗粒处理巨噬细胞，并测定促炎和抗炎细胞因子、一氧化氮（NO）和过氧化氢（HO）水平的产生。在BALB/c小鼠中进行了毒理学评估，并在角叉菜胶诱导的爪肿胀模型中评估了体内抗炎作用，并测量了促炎细胞因子的血清水平。结果表明，MCM-41-PbAE-DOX以剂量依赖方式显著降低NO和HO水平以及促炎细胞因子（IL-1β、IL-6和TNF-α），而不影响细胞活力或对小鼠产生毒性。相反，观察到角叉菜胶诱导的爪肿胀减轻和促炎细胞因子水平降低，这表明将DOX封装在MCM-41-PbAE纳米颗粒中的潜在优势，即可以在不损害健康细胞活力的情况下抑制炎症。
