de Souza Marina Guedes Fonseca, de Jesus Guedes Fabrícia Nunes, Tebaldi Marli Luiza, do Nascimento Alencar Éverton, Amaral-Machado Lucas, do Egito Eryvaldo Sócrates Tabosa, de Barros André Luis Branco, Soares Daniel Crístian Ferreira
Bioengineering Laboratory, Federal University of Itajubá, Rua Irmã Ivone Drumond, 200, Distrito Industrial II, Itabira 35903-087, Brazil.
Laboratory of Dispersed Systems (LaSiD), Department of Pharmacy, Federal University of Rio Grande do Norte (UFRN), Rua Gal. Gustavo Cordeiro de Farias, s/n, Petropolis, Natal 59010-180, Brazil.
Pharmaceutics. 2021 May 13;13(5):712. doi: 10.3390/pharmaceutics13050712.
Liposomes have become successful nanostructured systems used in clinical practices. These vesicles are able to carry important drug loadings with noteworthy stability. The aim of this work was to develop iron oxide-loaded stealth liposomes as a prospective alternative for the treatment of lung cancer. In this study, citric acid iron oxide nanoparticles (IONPs-Ac) were synthesized and encapsulated in stealth liposomes. Their cytotoxicity and selectivity against lung tumor cells were assessed. Stealth liposomal vesicles, with relevant content of IONPs-Ac, named ferri-liposomes (SL-IONPs-Ac), were produced with an average size of 200 nm. They displayed important cytotoxicity in a human lung cancer cells model (A549 cells), even at low concentrations, whereas free IONPs-Ac displayed adequate biocompatibility. Nevertheless, the treatment at the same concentration of ferri-liposomes against HEK-293 cells, a normal human cell lineage, was not significantly cytotoxic, revealing a probable lung tumor selectiveness of the fabricated formulation. Furthermore, from the flow cytometry studies, it was possible to infer that ferri-liposomes were able to induce A549 tumor cells death through apoptosis/ferroptosis processes, evidenced by a significant reduction of the mitochondrial membrane potential.
脂质体已成为临床实践中成功应用的纳米结构系统。这些囊泡能够携带重要的药物负载量，并具有显著的稳定性。这项工作的目的是开发负载氧化铁的隐形脂质体，作为治疗肺癌的一种潜在替代方法。在本研究中，合成了柠檬酸氧化铁纳米颗粒（IONPs-Ac）并将其包封在隐形脂质体中。评估了它们对肺肿瘤细胞的细胞毒性和选择性。制备了具有相关IONPs-Ac含量的隐形脂质体囊泡，称为铁脂质体（SL-IONPs-Ac），平均尺寸为200nm。它们在人肺癌细胞模型（A549细胞）中表现出重要的细胞毒性，即使在低浓度下也是如此，而游离的IONPs-Ac表现出良好的生物相容性。然而，相同浓度的铁脂质体对正常人类细胞系HEK-293细胞的处理并没有显著的细胞毒性，这表明所制备的制剂可能具有肺肿瘤选择性。此外，通过流式细胞术研究可以推断，铁脂质体能够通过凋亡/铁死亡过程诱导A549肿瘤细胞死亡，线粒体膜电位的显著降低证明了这一点。
