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针对胶质母细胞瘤多形性的 miRNA 治疗药物的靶向递送。

Targeted delivery of miRNA based therapeuticals in the clinical management of Glioblastoma Multiforme.

机构信息

Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P. O. Box 1982, Dammam 31441, Saudi Arabia.

Department of Pharmaceutics, School of Pharmaceutical Education and Research (SPER), Jamia Hamdard, New-Delhi, India; School of Pharmaceutical Sciences, Apeejay Stya University, Gurugram, Haryana, India.

出版信息

Semin Cancer Biol. 2021 Feb;69:391-398. doi: 10.1016/j.semcancer.2020.04.001. Epub 2020 Apr 14.

DOI:10.1016/j.semcancer.2020.04.001
PMID:32302695
Abstract

Glioblastoma multiforme (GBM) is the most aggressive (WHO grade IV) form of diffuse glioma endowed with tremendous invasive capacity. The availability of narrow therapeutic choices for GBM management adds to the irony, even the post-treatment median survival time is roughly around 14-16 months. Gene mutations seem to be cardinal to GBM formation, owing to involvement of amplified and mutated receptor tyrosine kinase (RTK)-encoding genes, leading to dysregulation of growth factor signaling pathways. Of-late, the role of different microRNAs (miRNAs) in progression and proliferation of GBM was realized, which lead to their burgeon potential applications for diagnostic and therapeutic purposes. miRNA signatures are intricately linked with onset and progression of GBM. Although, progression of GBM causes significant changes in the BBB to form BBTB, but still efficient passage of cancer therapeutics, including antibodies and miRNAs are prevented, leading to low bioavailability. Recent developments in the nanomedicine field provide novel approaches to manage GBM via efficient and brain targeted delivery of miRNAs either alone or as part of cytotoxic pharmaceutical composition, thereby modulating cell signaling in well predicted manner to promise positive therapeutic outcomes.

摘要

多形性胶质母细胞瘤(GBM)是最具侵袭性的弥漫性神经胶质瘤(WHO 分级 IV)。由于涉及扩增和突变的受体酪氨酸激酶(RTK)编码基因,导致生长因子信号通路失调,GBM 的形成似乎与基因突变密切相关。最近,人们意识到不同 microRNAs(miRNAs)在 GBM 的进展和增殖中的作用,这为其在诊断和治疗目的方面的潜在应用提供了依据。miRNA 特征与 GBM 的发生和进展密切相关。尽管 GBM 的进展会导致 BBB 发生显著变化,形成 BBTB,但仍会阻止包括抗体和 miRNAs 在内的癌症治疗药物的有效通过,导致其生物利用度低。纳米医学领域的最新进展为通过单独或作为细胞毒性药物组合物的一部分,通过有效的脑靶向 miRNA 传递来管理 GBM 提供了新的方法,从而以可预测的方式调节细胞信号,以保证积极的治疗效果。

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