Nanomedicine drug delivery systems are capable of transporting significant payloads to solid tumors. However, only a modest increase in antitumor efficacy relative to the standard of care has been observed. In this study, we demonstrate that a single dose of radiation or mild hyperthermia can substantially improve tumor uptake and distribution of nanotherapeutics, resulting in improved treatment efficacy. The delivery of nanomedicine was driven by a reduction in interstitial fluid pressure (IFP) and small perturbation of steady-state fluid flow. The transient effects on fluid dynamics in tumors with high IFP was also shown to dominate over immune cell endocytic capacity, another mechanism suspected of improving drug delivery. Furthermore, we demonstrate the specificity of this mechanism by showing that delivery of nanotherapeutics to low IFP tumors with high leukocyte infiltration does not benefit from pretreatment with radiation or heat. These results demonstrate that focusing on small perturbations to steady-state fluid dynamics, rather than large sustained effects or uncertain immune cell recruitment strategies, can impart a vulnerability to tumors with high IFP and enhance nanotherapeutic drug delivery and treatment efficacy.

中文翻译：

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辐射和热量通过调节瘤内流体动力学改善了纳米疗法的传递和功效。

纳米药物给药系统能够将大量有效载荷转运至实体瘤。然而，相对于护理标准，仅观察到抗肿瘤功效的适度增加。在这项研究中，我们证明了单剂量的放射疗法或轻度高温可以大大改善肿瘤吸收和纳米疗法的分布，从而提高治疗效果。纳米药物的输送是由组织间液压（IFP）的降低和稳态流体流动的较小扰动来驱动的。具有高IFP的肿瘤对流体动力学的短暂影响也显示出优于免疫细胞内吞能力，这是另一种改善药物传递的机制。此外，我们通过显示纳米治疗剂向具有高白细胞浸润的低IFP肿瘤的递送不会受益于辐射或热的预处理，证明了这种机制的特异性。这些结果表明，专注于对稳态流体动力学的小扰动，而不是持续的大作用或不确定的免疫细胞募集策略，可以使高IFP的肿瘤更加脆弱，并增强纳米治疗药物的递送和治疗功效。