Department of Experimental and Clinical Medicine, University "Magna Græcia" of Catanzaro Campus Universitario-Germaneto, Viale Europa, 88100, Catanzaro, Italy.
Department of Cardiac, Thoracic and Vascular Science and Public Health, University of Padova, 35128, Padua, Italy.
Drug Deliv Transl Res. 2023 Dec;13(12):3154-3168. doi: 10.1007/s13346-023-01378-9. Epub 2023 Jun 26.
Despite the efforts and advances done in the last few decades, cancer still remains one of the main leading causes of death worldwide. Nanomedicine and in particular extracellular vesicles are one of the most potent tools to improve the effectiveness of anticancer therapies. In these attempts, the aim of this work is to realize a hybrid nanosystem through the fusion between the M1 macrophages-derived extracellular vesicles (EVs-M1) and thermoresponsive liposomes, in order to obtain a drug delivery system able to exploit the intrinsic tumor targeting capability of immune cells reflected on EVs and thermoresponsiveness of synthetic nanovesicles. The obtained nanocarrier has been physicochemically characterized, and the hybridization process has been validated by cytofluorimetric analysis, while the thermoresponsiveness was in vitro confirmed through the use of a fluorescent probe. Tumor targeting features of hybrid nanovesicles were in vivo investigated on melanoma-induced mice model monitoring the accumulation in tumor site through live imaging and confirmed by cytofluorimetric analysis, showing higher targeting properties of hybrid nanosystem compared to both liposomes and native EVs. These promising results confirmed the ability of this nanosystem to combine the advantages of both nanotechnologies, also highlighting their potential use as effective and safe personalized anticancer nanomedicine.
尽管在过去几十年中已经做出了努力和进展，但癌症仍然是全球主要死亡原因之一。纳米医学，特别是细胞外囊泡，是提高抗癌疗法效果的最有力工具之一。在这些尝试中，这项工作的目的是通过将 M1 巨噬细胞衍生的细胞外囊泡 (EVs-M1) 与热响应脂质体融合，实现一种混合纳米系统，以获得一种能够利用免疫细胞内在的肿瘤靶向能力的药物输送系统，这种能力反映在 EVs 上，同时也利用合成纳米囊泡的热响应性。已经对所得纳米载体进行了物理化学表征，并通过细胞荧光分析验证了杂交过程，而通过使用荧光探针在体外证实了热响应性。通过活体成像监测肿瘤部位的积累，在黑色素瘤诱导的小鼠模型中对杂交纳米囊泡的肿瘤靶向特征进行了体内研究，并通过细胞荧光分析进行了证实，与脂质体和天然 EVs 相比，杂交纳米系统显示出更高的靶向特性。这些有希望的结果证实了该纳米系统结合两种纳米技术优势的能力，还突出了其作为有效和安全的个性化抗癌纳米医学的潜在用途。
