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用于三阴性乳腺癌细胞高效体外药物递送的自推进、蛋白质结合磁性纳米机器人。

Self-propelling, protein-bound magnetic nanobots for efficient in vitro drug delivery in triple negative breast cancer cells.

作者信息

Naikwadi Neha, Paul Milan, Biswas Swati, Chitlange Sohan, Wavhale Ravindra

机构信息

Department of Pharmaceutical Chemistry, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, India.

Nanomedicine Research Laboratory, Department of Pharmacy, Birla Institute of Technology &, Science-Pilani, Hyderabad Campus, Medchal, Hyderabad, 500078, Telangana, India.

出版信息

Sci Rep. 2024 Dec 28;14(1):31547. doi: 10.1038/s41598-024-83393-5.

Abstract

The emergence of self-propelling magnetic nanobots represents a significant advancement in the field of drug delivery. These magneto-nanobots offer precise control over drug targeting and possess the capability to navigate deep into tumor tissues, thereby addressing multiple challenges associated with conventional cancer therapies. Here, Fe-GSH-Protein-Dox, a novel self-propelling magnetic nanobot conjugated with a biocompatible protein surface and loaded with doxorubicin for the treatment of triple-negative breast cancer (TNBC), is reported. The self-propulsion of magnetic nanobots occurs due to a catalytic interaction between FeO nanoparticles and hydrogen peroxide. This interaction results in generation of O bubbles and high-speed propulsion in blood serum. Cell entry kinetic studies confirmed higher internalization of the drug into TNBC cells with Fe-GSH-Protein-Dox nanobots, resulting in a lower observed IC and higher potential to kill cancer cells compared to free doxorubicin. Moreover, fluorescence imaging studies confirmed an increase in the production of reactive oxygen species, leading to maximum cellular damage. Endocytosis studies elucidate the mechanism of cellular internalization, revealing clathrin-mediated endocytosis, while the cell cycle study demonstrates significant cell cycle arrest in the G2-M phase. Thus, the designed protein-conjugated self-propelling magnetic nanobots have the potential to develop into a novel drug delivery platform for clinical applications.

摘要

自推进式磁性纳米机器人的出现代表了药物递送领域的一项重大进展。这些磁纳米机器人可对药物靶向进行精确控制,并具备深入肿瘤组织的导航能力,从而应对传统癌症治疗相关的多重挑战。在此,报道了一种新型的自推进式磁性纳米机器人Fe-GSH-蛋白质-阿霉素,其表面结合了生物相容性蛋白质并负载阿霉素用于治疗三阴性乳腺癌(TNBC)。磁性纳米机器人的自推进是由于FeO纳米颗粒与过氧化氢之间的催化相互作用所致。这种相互作用导致在血清中产生氧气泡并实现高速推进。细胞摄取动力学研究证实,与游离阿霉素相比,Fe-GSH-蛋白质-阿霉素纳米机器人使药物进入TNBC细胞的内化作用更强,导致观察到的半数抑制浓度更低且杀死癌细胞的潜力更高。此外,荧光成像研究证实活性氧的产生增加,导致最大程度的细胞损伤。内吞作用研究阐明了细胞内化的机制,揭示了网格蛋白介导的内吞作用,而细胞周期研究表明在G2-M期有明显的细胞周期阻滞。因此,所设计的蛋白质共轭自推进式磁性纳米机器人有潜力发展成为一种用于临床应用的新型药物递送平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf80/11682353/c496555aa713/41598_2024_83393_Fig1_HTML.jpg

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