Iessi Elisabetta, Logozzi Mariantonia, Lugini Luana, Azzarito Tommaso, Federici Cristina, Spugnini Enrico Pierluigi, Mizzoni Davide, Di Raimo Rossella, Angelini Daniela F, Battistini Luca, Cecchetti Serena, Fais Stefano
a Anti-Tumour Drugs Section, Department of Drug Research and Medicines Evaluation , National Institute of Health , Rome , Italy.
b SAFU Department , Regina Elena Cancer Institute , Rome , Italy.
J Enzyme Inhib Med Chem. 2017 Dec;32(1):648-657. doi: 10.1080/14756366.2017.1292263.
Specifically targeted drug delivery systems with low immunogenicity and toxicity are deemed to increase efficacy of cancer chemotherapy. Acridine Orange (AO) is an acidophilic dye with a strong tumoricidal action following excitation with a light source at 466 nm. However, to date the clinical use of AO is limited by the potential side effects elicited by systemic administration. The endogenous nanocarrier exosomes have been recently introduced as a natural delivery system for therapeutic molecules. In this article, we show the outcome of the administration to human melanoma cells of AO charged Exosomes (Exo-AO), in both monolayer and spheroid models. The results showed an extended drug delivery time of Exo-AO to melanoma cells as compared to the free AO, improving the cytotoxicity of AO. This study shows that Exo-AO have a great potential for a real exploitation as a new theranostic approach against tumors based on AO delivered through the exosomes.
具有低免疫原性和毒性的特异性靶向给药系统被认为可提高癌症化疗的疗效。吖啶橙(AO)是一种嗜酸性染料,在466nm光源激发后具有强大的杀肿瘤作用。然而,迄今为止,AO的临床应用受到全身给药引起的潜在副作用的限制。内源性纳米载体外泌体最近已被引入作为治疗分子的天然递送系统。在本文中,我们展示了在单层和球体模型中,将带电荷的AO外泌体(Exo-AO)施用于人黑色素瘤细胞的结果。结果表明,与游离AO相比,Exo-AO向黑色素瘤细胞的药物递送时间延长,提高了AO的细胞毒性。本研究表明,Exo-AO作为一种基于通过外泌体递送AO的新型肿瘤诊疗方法具有很大的实际应用潜力。