胶质母细胞瘤管理的纳米治疗药物递送选择综述

W. H. Pentz, Vincenzo J. Pizzuti, Matthew E. Halbert, Tritan J. Plute, P. Lockman, S. Sprowls
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摘要

胶质母细胞瘤是最常见的原发性恶性脑肿瘤,由于其极端的细胞异质性、治疗耐药性和复发,几乎在所有病例中都是致命的。对脑肿瘤进行治疗的主要障碍是血脑屏障(BBB),这是脑实质和体循环之间严格调节的血管屏障,阻止了原本有益的化疗药物向中枢神经系统肿瘤的分布。为了克服血脑屏障之外的药物传递障碍,纳米颗粒制剂已经走到了前沿,在临床前观察中取得了成功,但尚未很好地转化为临床环境。总之,这篇综述文章讨论了脑屏障引起的脑肿瘤和药物递送的挑战,探讨了纳米颗粒配方对脑肿瘤递送的好处,描述了这些配方所具有的使其具有吸引力的治疗策略的特征,并提供了在胶质瘤治疗方案中实施纳米颗粒的临床前示例。此外,我们探讨了与临床翻译相关的陷阱,并总结了针对克服这些问题的评论。
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An Overview of Nanotherapeutic Drug Delivery Options for the Management of Glioblastoma
Glioblastoma is the most common primary, malignant brain tumor that remains uniformly lethal in nearly all cases as a result of extreme cellular heterogeneity, treatment resistance, and recurrence. A major hurdle in therapeutic delivery to brain tumors is the blood–brain barrier (BBB), which is the tightly regulated vascular barrier between the brain parenchyma and systemic circulation that prevents distribution of otherwise beneficial chemotherapeutics to central nervous system tumors. To overcome the obstacle of drug delivery beyond the BBB, nanoparticle formulations have come to the forefront, having demonstrated success in preclinical observations, but have not translated well into the clinical setting. In summary, this review article discusses brain tumors and challenges for drug delivery caused by the BBB, explores the benefits of nanoparticle formulations for brain tumor delivery, describes the characteristics these formulations possess that make them attractive therapeutic strategies, and provides preclinical examples that implement nanoparticles within glioma treatment regimens. Additionally, we explore the pitfalls associated with clinical translation and conclude with remarks geared toward overcoming these issues.
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