Novoselova M V, Shramova E I, Sergeeva O V, Shcherbinina E Y, Perevoschikov S V, Melnikov P, Griaznova O Yu, Sergeev I S, Konovalova E V, Schulga A A, Proshkina G M, Zatsepin T S, Deyev S M, Gorin D A
Skolkovo Institute of Science and Technology, Moscow 121205, Russia.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow 117997, Russia.
Nanomedicine. 2023 Jan;47:102612. doi: 10.1016/j.nano.2022.102612. Epub 2022 Oct 13.
Nanomedicine has revolutionized the available treatment options during the last decade, but poor selectivity of targeted drug delivery and release is still poses a challenge. In this study, doxorubicin (DOX) and magnetite nanoparticles were encapsulated by freezing-induced loading, coated with polymeric shell bearing two bi-layers of polyarginine/dextran sulphate and finally modified with HER2-specific DARPin proteins. We demonstrated that the enhanced cellular uptake of these nanocarriers predominantly occurs by SKOV-3 (HER2+) cells, in comparison to CHO (HER2-) cells, together with the controlled DOX release using low intensity focused ultrasound (LIFU). In addition, a good ability of DARPin+ capsules to accumulate in the tumor and the possibility of combination therapy with LIFU were demonstrated. A relatively high sensitivity of the obtained nanocarriers to LIFU and their preferential interactions with mitochondria in cancer cells make these carriers promising candidates for cancer treatment, including novel approaches to overcome drug resistance.
在过去十年中，纳米医学彻底改变了现有的治疗选择，但靶向药物递送和释放的选择性差仍然是一个挑战。在本研究中，通过冷冻诱导负载将阿霉素（DOX）和磁铁矿纳米颗粒封装起来，用带有两层聚精氨酸/硫酸葡聚糖的聚合物外壳进行包被，最后用HER2特异性DARPin蛋白进行修饰。我们证明，与CHO（HER2-）细胞相比，这些纳米载体在SKOV-3（HER2+）细胞中的细胞摄取增强，同时使用低强度聚焦超声（LIFU）可实现DOX的可控释放。此外，还证明了DARPin+胶囊在肿瘤中积累的良好能力以及与LIFU联合治疗的可能性。所获得的纳米载体对LIFU具有较高的敏感性，并且它们与癌细胞中的线粒体具有优先相互作用，这使得这些载体成为癌症治疗的有前景的候选者，包括克服耐药性的新方法。
