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纳米医学治疗脑癌和与年龄相关的神经退行性疾病的益处和局限性。

Benefits and limitations of nanomedicine treatment of brain cancers and age-dependent neurodegenerative disorders.

机构信息

Institute of Physiologically Active Compounds of the Russian Academy of Sciences, 1, Severnii pr., Chernogolovka 142432, Russia.

School of Health Sciences, Flinders University of South Australia, Bedford Park, SA 5042, Australia.

出版信息

Semin Cancer Biol. 2022 Nov;86(Pt 2):805-833. doi: 10.1016/j.semcancer.2022.06.011. Epub 2022 Jun 30.

Abstract

The treatment of central nervous system (CNS) malignancies, including brain cancers, is limited by a number of obstructions, including the blood-brain barrier (BBB), the heterogeneity and high invasiveness of tumors, the inaccessibility of tissues for early diagnosis and effective surgery, and anti-cancer drug resistance. Therapies employing nanomedicine have been shown to facilitate drug penetration across the BBB and maintain biodistribution and accumulation of therapeutic agents at the desired target site. The application of lipid-, polymer-, or metal-based nanocarriers represents an advanced drug delivery system for a growing group of anti-cancer chemicals. The nanocarrier surface is designed to contain an active ligand (cancer cell marker or antibody)-binding structure which can be modified to target specific cancer cells. Glioblastoma, ependymoma, neuroblastoma, medulloblastoma, and primary CNS lymphomas were recently targeted by easily absorbed nanocarriers. The metal- (such as transferrin drug-loaded systems), polymer- (nanocapsules and nanospheres), or lipid- (such as sulfatide-containing nanoliposomes)-based nano-vehicles were loaded with apoptosis- and/or ferroptosis-stimulating agents and demonstrated promising anti-cancer effects. This review aims to discuss effective nanomedicine approaches designed to overcome the current limitations in the therapy of brain cancers and age-dependent neurodegenerative disorders. To accent current obstacles for successful CNS-based cancer therapy, we discuss nanomedicine perspectives and limitations of nanodrug use associated with the specificity of nervous tissue characteristics and the effects nanocarriers have on cognition.

摘要

中枢神经系统(CNS)恶性肿瘤的治疗,包括脑癌,受到多种障碍的限制,包括血脑屏障(BBB)、肿瘤的异质性和高侵袭性、组织早期诊断和有效手术的不可及性,以及抗癌药物耐药性。纳米医学治疗方法已被证明可以促进药物穿透血脑屏障,并维持治疗剂在所需靶部位的生物分布和积累。基于脂质、聚合物或金属的纳米载体的应用代表了一组不断增长的抗癌化学物质的先进药物传递系统。纳米载体表面设计包含一个活性配体(癌细胞标志物或抗体结合结构),可以进行修饰以靶向特定的癌细胞。胶质母细胞瘤、室管膜瘤、神经母细胞瘤、髓母细胞瘤和原发性中枢神经系统淋巴瘤最近成为易于吸收的纳米载体的靶标。基于金属(如转铁蛋白载药系统)、聚合物(纳米胶囊和纳米球)或脂质(如含硫脂的纳米脂质体)的纳米载体装载了凋亡和/或铁死亡刺激剂,并表现出有前途的抗癌效果。本综述旨在讨论旨在克服脑癌和与年龄相关的神经退行性疾病治疗当前局限性的有效纳米医学方法。为了强调基于中枢神经系统的癌症治疗成功的当前障碍,我们讨论了纳米医学的观点和纳米药物使用的局限性,这些与神经组织特征的特异性以及纳米载体对认知的影响有关。

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