Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
Université Grenoble Alpes, Etablissement Français du Sang, IAB, Inserm U1209 & CNRS UMR5309, Grenoble, France.
Nanomedicine. 2018 Aug;14(6):1853-1865. doi: 10.1016/j.nano.2018.05.001. Epub 2018 May 17.
One of the major factors limiting the effectiveness of cancer chemotherapy is inefficient drug delivery. Systems enabling efficient delivery and enhanced intracellular uptake appear particularly promising in this respect. Virus-like particle, adenoviral dodecahedron (Dd), employs receptor-mediated endocytosis for cell penetration and is able to deliver intracellularly dozens of cargo molecules attached to one particle. We focused on studying Dd properties in the context of cancer treatment, showing that intratumoral injection of Dd, assessed in mouse xenograft model, results in vector accumulation in tumor without spreading in off-target organs. Moreover, we demonstrated that Dd is a promising vector targeting leukocytes and drug-resistant cancer cells. Dd uptake by human blood cells analyzed in vitro indicated the preference for leukocytes in comparison to red blood cells and platelets. Furthermore, internalization of Dd-doxorubicin conjugate by drug-resistant cells leads to increased nuclear accumulation of doxorubicin and significant enhancement of cytotoxicity against target cancer cells.
限制癌症化疗效果的主要因素之一是药物递送效率低下。在这方面，能够实现有效递送和增强细胞内摄取的系统似乎特别有前景。病毒样颗粒、腺病毒十二面体 (Dd) 通过受体介导的内吞作用穿透细胞，并能够将数十个附着在一个颗粒上的货物分子递送至细胞内。我们专注于研究 Dd 在癌症治疗中的特性，表明在小鼠异种移植模型中评估的肿瘤内注射 Dd 会导致载体在肿瘤中积累，而不会在非靶器官中扩散。此外，我们证明 Dd 是一种有前途的靶向白细胞和耐药癌细胞的载体。体外分析人血细胞对 Dd 的摄取表明，与红细胞和血小板相比，白细胞对 Dd 的摄取具有偏好性。此外，耐药细胞对 Dd-阿霉素缀合物的内化导致阿霉素在核内的积累增加，并显著增强对靶癌细胞的细胞毒性。
