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Stiffness of targeted layer-by-layer nanoparticles impacts elimination half-life, tumor accumulation, and tumor penetration [Applied Biological Sciences]
Proceedings of the National Academy of Sciences of the United States of America ( IF 11.1 ) Pub Date : 2021-10-19 , DOI: 10.1073/pnas.2104826118
Stephanie M Kong 1, 2 , Daniel F Costa 1 , Anna Jagielska 3 , Krystyn J Van Vliet 3, 4 , Paula T Hammond 2, 5
Affiliation  

Nanoparticle (NP) stiffness has been shown to significantly impact circulation time and biodistribution in anticancer drug delivery. In particular, the relationship between particle stiffness and tumor accumulation and penetration in vivo is an important phenomenon to consider in optimizing NP-mediated tumor delivery. Layer-by-layer (LbL) NPs represent a promising class of multifunctional nanoscale drug delivery carriers. However, there has been no demonstration of the versatility of LbL systems in coating systems with different stiffnesses, and little is known about the potential role of LbL NP stiffness in modulating in vivo particle trafficking, although NP modulus has been recently studied for its impact on pharmacokinetics. LbL nanotechnology enables NPs to be functionalized with uniform coatings possessing molecular tumor-targeting properties, independent of the NP core stiffness. Here, we report that the stiffness of LbL NPs is directly influenced by the mechanical properties of its underlying liposomal core, enabling the modulation and optimization of LbL NP stiffness while preserving LbL NP outer layer tumor-targeting and stealth properties. We demonstrate that the stiffness of LbL NPs has a direct impact on NP pharmacokinetics, organ and tumor accumulation, and tumor penetration—with compliant LbL NPs having longer elimination half-life, higher tumor accumulation, and higher tumor penetration. Our findings underscore the importance of NP stiffness as a design parameter in enhancing the delivery of LbL NP formulations.



中文翻译:

靶向逐层纳米粒子的刚度影响消除半衰期、肿瘤积累和肿瘤穿透 [应用生物科学]

纳米颗粒 (NP) 刚度已被证明显着影响抗癌药物递送中的循环时间和生物分布。特别是,粒子刚度与体内肿瘤积累和穿透之间的关系是优化 NP 介导的肿瘤递送时需要考虑的重要现象。逐层(LbL)NPs代表了一类有前途的多功能纳米级药物递送载体。然而,没有证明 LbL 系统在具有不同刚度的涂层系统中的多功能性,并且关于 LbL NP 刚度在调节体内颗粒运输中的潜在作用知之甚少,尽管最近研究了 NP 模量对药代动力学。LbL 纳米技术使 NP 能够通过具有分子肿瘤靶向特性的均匀涂层功能化,而与 NP 核心刚度无关。在这里,我们报告 LbL NPs 的刚度直接受其底层脂质体核心的机械性能影响,从而能够调节和优化 LbL NP 刚度,同时保持 LbL NP 外层肿瘤靶向和隐身特性。我们证明了 LbL NPs 的刚度对 NP 药代动力学、器官和肿瘤积累以及肿瘤穿透具有直接影响——顺从的 LbL NPs 具有更长的消除半衰期、更高的肿瘤积累和更高的肿瘤穿透性。我们的研究结果强调了 NP 刚度作为设计参数在增强 LbL NP 配方输送方面的重要性。我们报告说,LbL NPs 的刚度直接受到其底层脂质体核心的机械特性的影响,从而能够在保持 LbL NP 外层肿瘤靶向和隐身特性的同时调节和优化 LbL NP 刚度。我们证明了 LbL NPs 的刚度对 NP 药代动力学、器官和肿瘤积累以及肿瘤穿透具有直接影响——顺从的 LbL NPs 具有更长的消除半衰期、更高的肿瘤积累和更高的肿瘤穿透性。我们的研究结果强调了 NP 刚度作为设计参数在增强 LbL NP 配方输送方面的重要性。我们报告说,LbL NPs 的刚度直接受到其底层脂质体核心的机械特性的影响,从而能够在保持 LbL NP 外层肿瘤靶向和隐身特性的同时调节和优化 LbL NP 刚度。我们证明了 LbL NPs 的刚度对 NP 药代动力学、器官和肿瘤积累以及肿瘤穿透具有直接影响——顺从的 LbL NPs 具有更长的消除半衰期、更高的肿瘤积累和更高的肿瘤穿透性。我们的研究结果强调了 NP 刚度作为设计参数在增强 LbL NP 配方输送方面的重要性。能够调节和优化 LbL NP 刚度,同时保留 LbL NP 外层肿瘤靶向和隐身特性。我们证明了 LbL NPs 的刚度对 NP 药代动力学、器官和肿瘤积累以及肿瘤穿透具有直接影响——顺从的 LbL NPs 具有更长的消除半衰期、更高的肿瘤积累和更高的肿瘤穿透性。我们的研究结果强调了 NP 刚度作为设计参数在增强 LbL NP 配方输送方面的重要性。能够调节和优化 LbL NP 刚度,同时保留 LbL NP 外层肿瘤靶向和隐身特性。我们证明了 LbL NPs 的刚度对 NP 药代动力学、器官和肿瘤积累以及肿瘤穿透具有直接影响——顺从的 LbL NPs 具有更长的消除半衰期、更高的肿瘤积累和更高的肿瘤穿透性。我们的研究结果强调了 NP 刚度作为设计参数在增强 LbL NP 配方输送方面的重要性。

更新日期:2021-10-15
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