Polymer/magnetite carriers functionalized by HER2-DARPin: Avoiding lysosomes during internalization and controlled toxicity of doxorubicin by focused ultrasound induced release

IF 4.7 4区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
M.V. Novoselova PhD , E.I. Shramova PhD , O.V. Sergeeva PhD , E.Y. Shcherbinina MSc , S.V. Perevoschikov MSc , P. Melnikov PhD , O.Yu. Griaznova BSc , I.S. Sergeev MSc , E.V. Konovalova MSc , A.A. Schulga PhD , G.M. Proshkina PhD , T.S. Zatsepin PhD , S.M. Deyev DSc , D.A. Gorin DSc
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引用次数: 1

Abstract

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.

Abstract Image

HER2-DARPin功能化的聚合物/磁铁矿载体:在阿霉素内化过程中避免溶酶体并通过聚焦超声诱导释放控制其毒性
在过去的十年中,纳米医学已经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。在这项研究中,阿霉素和磁铁矿纳米颗粒通过冷冻诱导负载被包裹,包被带有两层聚精氨酸/葡聚糖硫酸盐的聚合物外壳,最后用her2特异性DARPin蛋白修饰。我们证明,与CHO (HER2−)细胞相比,SKOV-3 (HER2+)细胞主要增强了这些纳米载体的细胞摄取,同时使用低强度聚焦超声(LIFU)控制DOX释放。此外,还证实了DARPin+胶囊在肿瘤中具有良好的蓄积能力,并有可能与LIFU联合治疗。所获得的纳米载体对LIFU的相对高敏感性及其与癌细胞线粒体的优先相互作用使这些载体成为癌症治疗的有希望的候选者,包括克服耐药性的新方法。
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来源期刊
CiteScore
8.10
自引率
3.60%
发文量
104
审稿时长
4.6 months
期刊介绍: Nanomedicine: Nanotechnology, Biology and Medicine (NBM) is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
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