利用人体 H 铁蛋白纳米颗粒给药的挑战:突破生理限制。

Alberto Macone, Chiara Cappelletti, Alessio Incocciati, Roberta Piacentini, Sofia Botta, Alberto Boffi, Alessandra Bonamore
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引用次数: 0

摘要

在过去二十年里,铁蛋白已成为一种前景广阔的纳米给药颗粒,促进了众多能够封装多种治疗药物的原型的开发。这些基于铁蛋白的纳米颗粒对各种分子靶点具有选择性,并以其潜在的生物相容性、独特的对称结构和高度可控的尺寸而与众不同。铁蛋白纳米粒子内部中空,可有效封装各种治疗药物,提高药物的输送和疗效。尽管铁蛋白具有这些令人期待的特性,但预期的临床进展尚未完全实现。铁蛋白是一种生理蛋白质,在健康和疾病中都发挥着重要作用,因此在用作给药系统时会对生理学产生意想不到的影响。许多研究都没有彻底评估铁蛋白外壳在体内给药时的药代动力学特性,忽略了生物分布、清除、细胞贩运和免疫反应等关键方面。应对这些挑战对于实现从实验室到临床的理想过渡至关重要。生物分布研究需要考虑铁蛋白在特定器官(肝脏、脾脏和肾脏)的自然积累,这可能会导致脱靶效应。此外,还必须阐明清除和细胞贩运机制,以优化铁蛋白纳米颗粒的输送并降低其潜在毒性。此外,了解外源铁蛋白引起的免疫反应对于减轻不良反应和提高疗效也至关重要。全面了解这些生理限制因素以及创新的解决方案对于充分发挥铁蛋白纳米颗粒的治疗潜力至关重要,从而为其成功的临床转化铺平道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Challenges in Exploiting Human H Ferritin Nanoparticles for Drug Delivery: Navigating Physiological Constraints.

Over the past two decades, ferritin has emerged as a promising nanoparticle for drug delivery, catalyzing the development of numerous prototypes capable of encapsulating a wide array of therapeutic agents. These ferritin-based nanoparticles exhibit selectivity for various molecular targets and are distinguished by their potential biocompatibility, unique symmetrical structure, and highly controlled size. The hollow interior of ferritin nanoparticles allows for efficient encapsulation of diverse therapeutic agents, enhancing their delivery and effectiveness. Despite these promising features, the anticipated clinical advancements have yet to be fully realized. As a physiological protein with a central role in both health and disease, ferritin can exert unexpected effects on physiology when employed as a drug delivery system. Many studies have not thoroughly evaluated the pharmacokinetic properties of the ferritin protein shell when administered in vivo, overlooking crucial aspects such as biodistribution, clearance, cellular trafficking, and immune response. Addressing these challenges is crucial for achieving the desired transition from bench to bedside. Biodistribution studies need to account for ferritin's natural accumulation in specific organs (liver, spleen, and kidneys), which may lead to off-target effects. Moreover, the mechanisms of clearance and cellular trafficking must be elucidated to optimize the delivery and reduce potential toxicity of ferritin nanoparticles. Additionally, understanding the immune response elicited by exogenous ferritin is essential to mitigate adverse reactions and enhance therapeutic efficacy. A comprehensive understanding of these physiological constraints, along with innovative solutions, is essential to fully realize the therapeutic potential of ferritin nanoparticles paving the way for their successful clinical translation.

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