Nanoplatelets modified with RVG for targeted delivery of miR-375 and temozolomide to enhance gliomas therapy.

IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Nanobiotechnology Pub Date : 2024-10-15 DOI:10.1186/s12951-024-02895-6
Tingting Yang, Nan Zhang, Yuanyuan Liu, Ruyue Yang, Zhaoyi Wei, Futai Liu, Dan Song, Longwei Wang, Jiangyan Wei, Yuanpei Li, Deliang Shen, Gaofeng Liang
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Abstract

Gliomas are one of the most frequent primary brain tumors and pose a serious threat to people's lives and health. Platelets, a crucial component of blood, have been applied as drug delivery carriers for disease diagnosis and treatment. In this study, we designed engineered nanoplatelets for targeted delivery of therapeutic miR-375 and temozolomide (TMZ, a first-line glioma treatment agent) to enhance glioma therapy. Nanoplatelets were prepared through mild ultrasound, TMZ and miR-375 were co-loaded through ultrasound and electrostatic interactions, respectively, to combine chemotherapy with gene therapy against glioma. To improve the blood brain barrier (BBB) crossing efficiency and glioma targeting ability, the nanoplatelets were modified with central nervous system-specific rabies viral glycoprotein peptide (RVG) through thiol-maleimide click reaction. The RVG modified nanoplatelets co-loaded TMZ and miR-375 (NR/TMZ/miR-375) not only inherited the good stability and remarkable biocompatibility of platelets, but also promoted the cellular uptake and penetration of glioma tissues, and effectively induced cell apoptosis to enhance the therapeutic effect of drugs. In vivo studies showed that NR/TMZ/miR-375 significantly increased the circulation time of TMZ, and exhibited superior combined antitumor effects. In summary, this multifunctional 'natural' nanodrug delivery system provides a potent, scalable, and safety approach for platelet-based combined cancer chemotherapy and gene therapy.

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用 RVG 修饰的纳米颗粒可靶向输送 miR-375 和替莫唑胺,从而增强胶质瘤的治疗效果。
胶质瘤是最常见的原发性脑肿瘤之一,严重威胁着人们的生命和健康。血小板是血液的重要组成部分,已被用作疾病诊断和治疗的给药载体。在这项研究中,我们设计了用于靶向递送治疗药物 miR-375 和替莫唑胺(TMZ,一种一线胶质瘤治疗药物)的工程纳米小板,以提高胶质瘤的治疗效果。研究人员通过温和的超声波制备了纳米颗粒,并分别通过超声波和静电相互作用共同负载了TMZ和miR-375,从而将化疗和基因治疗结合起来,共同对抗胶质瘤。为了提高血脑屏障(BBB)穿越效率和胶质瘤靶向能力,纳米颗粒通过硫醇-马来酰亚胺点击反应修饰了中枢神经系统特异性狂犬病毒糖蛋白肽(RVG)。RVG修饰的共载TMZ和miR-375的纳米小板(NR/TMZ/miR-375)不仅继承了小板良好的稳定性和显著的生物相容性,还能促进胶质瘤组织的细胞摄取和穿透,有效诱导细胞凋亡,增强药物的治疗效果。体内研究表明,NR/TMZ/miR-375 能显著延长 TMZ 的循环时间,表现出卓越的联合抗肿瘤效果。总之,这种多功能 "天然 "纳米给药系统为基于血小板的癌症化疗和基因治疗联合疗法提供了一种有效、可扩展且安全的方法。
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来源期刊
Journal of Nanobiotechnology
Journal of Nanobiotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
13.90
自引率
4.90%
发文量
493
审稿时长
16 weeks
期刊介绍: Journal of Nanobiotechnology is an open access peer-reviewed journal communicating scientific and technological advances in the fields of medicine and biology, with an emphasis in their interface with nanoscale sciences. The journal provides biomedical scientists and the international biotechnology business community with the latest developments in the growing field of Nanobiotechnology.
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