Mphages and the Blood-Brain Barrier: A Review

Tomáš Maľarik, K. Bhide, Lea Talpašová, Mangesh Bhide
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Abstract

The blood-brain barrier (BBB) is a protective barrier that prevents most substances from entering the brain from the bloodstream, including bacteria and viruses. Unfortunately, this restriction also applies to 99.9 % of therapeutics, posing significant challenges in the treatment of brain diseases. Overcoming this barrier is critical for effective treatment of neurological disorders. Several drug delivery systems are being developed to improve transport of therapeutic agent across the BBB. For example, nanoparticles (liposomes, polymeric nanoparticles, dendrimers), nanocarriers (micelles, nanogels), protein-based delivery (penetrating peptides, exosomes), focused ultrasound, and most recently, a filamentous phage based nanocarriers. Filamentous bacteriophages are viruses that infect bacteria and are not designed to infect eukaryotic cells. Recent evidence suggests that filamentous bacteriophages, such as M13, can cross BBB and enter the central nervous system (CNS). Researchers have been investigating the potential use of M13 as drug carriers, including the delivery of therapeutic agents to the brain. This entails modifying the bacteriophages to carry payloads such as drugs and using them as a delivery system. The BBB’s complexity and the potential risks associated with changing it necessitate careful consideration in the development of such strategies. M13 nanocarrier development is ongoing, and advancements may lead to new therapeutic options for treating infections in the CNS. However, it is important to note that this field is still in its infancy, and more research is needed to assess the feasibility and safety of using modified bacteriophages to cross the BBB. This brief review attempts to compile current research on the potential use of bacteriophages for drug transport across the BBB.
噬菌体与血脑屏障:回顾
血脑屏障(BBB)是一道保护屏障,可阻止大多数物质(包括细菌和病毒)从血液进入大脑。不幸的是,这一限制也适用于 99.9% 的治疗药物,这给脑部疾病的治疗带来了巨大挑战。克服这一障碍对于有效治疗神经系统疾病至关重要。目前正在开发几种给药系统,以改善治疗药物通过 BBB 的运输。例如,纳米颗粒(脂质体、聚合物纳米颗粒、树枝状聚合物)、纳米载体(胶束、纳米凝胶)、基于蛋白质的给药(穿透肽、外泌体)、聚焦超声,以及最近出现的基于丝状噬菌体的纳米载体。丝状噬菌体是一种感染细菌的病毒,并不是用来感染真核细胞的。最近的证据表明,丝状噬菌体(如 M13)可以穿过 BBB 进入中枢神经系统(CNS)。研究人员一直在研究 M13 作为药物载体的潜在用途,包括向大脑输送治疗药物。这就需要对噬菌体进行改造,使其携带药物等有效载荷,并将其用作输送系统。由于 BBB 的复杂性以及改变 BBB 所带来的潜在风险,在开发此类战略时必须慎重考虑。M13 纳米载体的开发正在进行中,其进展可能会为治疗中枢神经系统感染带来新的治疗方案。但必须指出的是,这一领域仍处于起步阶段,需要更多的研究来评估使用改良噬菌体穿越 BBB 的可行性和安全性。这篇简短的综述试图梳理目前关于噬菌体跨 BBB 转运药物的潜在用途的研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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