Abstract Nanoscale drug delivery systems (NDDS) have shown great potential in tumor treatment due to its unique advantages, especially its unique enhanced permeability and retention effect (EPR) in solid tumors. Therefore, NDDS have been extensively explored in recent years. However, current NDDS did not achieve satisfied clinical therapeutic effect against to tumor treatment. This is mainly ascribed to two reasons. One is that nanocarriers would inevitably encounter a series of physiological and pathological barriers in vivo , leading to low drug transport efficiency. The other is that tumor stroma pose a huge obstruction to tumor therapy, nanotherapeutics just focus on the tumor cells themselves are insufficient for complete tumor eradication. Here in this review, we first outlining sequential biological obstacles encountered by nanocarriers from three levels of blood, tumor tissue and tumor cells. Then, we give a detailed discussion of the role of tumor stroma, and highlight the therapeutic resistances mediated by tumor stroma. In light of these formidable barriers, we provide promising approaches to overcome each barrier or remodel stroma through innovative NDDS design. Finally, we give proposals and considerations of NDDS design, and then discuss several existing challenges and further opportunities of NDDS in clinical application. This review seeks to provide guidelines for optimizing NDDS design through mitigation of biological barriers to efficient tumor therapy.

中文翻译：

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基于体内复杂生物屏障的纳米载体设计用于肿瘤治疗

摘要 纳米药物递送系统（NDDS）由于其独特的优势，尤其是其在实体瘤中独特的增强渗透性和保留效应（EPR），在肿瘤治疗中显示出巨大的潜力。因此，近年来对NDDS进行了广泛的探索。然而，目前的NDDS对肿瘤的治疗并没有达到满意的临床治疗效果。这主要归因于两个原因。一个是纳米载体在体内不可避免地会遇到一系列生理和病理障碍，导致药物转运效率低下。二是肿瘤基质对肿瘤治疗构成巨大阻碍，纳米治疗仅针对肿瘤细胞本身不足以彻底根除肿瘤。在这篇评论中，我们首先从血液、肿瘤组织和肿瘤细胞三个层面概述了纳米载体遇到的连续生物学障碍。然后，我们详细讨论了肿瘤基质的作用，并强调了肿瘤基质介导的治疗耐药性。鉴于这些巨大的障碍，我们提供了有前途的方法来克服每个障碍或通过创新的 NDDS 设计改造基质。最后，我们给出了 NDDS 设计的建议和考虑，然后讨论了 NDDS 在临床应用中的几个现有挑战和进一步的机会。本综述旨在为通过减轻有效肿瘤治疗的生物障碍来优化 NDDS 设计提供指南。并强调由肿瘤基质介导的治疗耐药性。鉴于这些巨大的障碍，我们提供了有前途的方法来克服每个障碍或通过创新的 NDDS 设计改造基质。最后，我们给出了 NDDS 设计的建议和考虑，然后讨论了 NDDS 在临床应用中的几个现有挑战和进一步的机会。本综述旨在为通过减轻有效肿瘤治疗的生物障碍来优化 NDDS 设计提供指南。并强调由肿瘤基质介导的治疗耐药性。鉴于这些巨大的障碍，我们提供了有前途的方法来克服每个障碍或通过创新的 NDDS 设计改造基质。最后，我们给出了 NDDS 设计的建议和考虑，然后讨论了 NDDS 在临床应用中的几个现有挑战和进一步的机会。本综述旨在为通过减轻有效肿瘤治疗的生物障碍来优化 NDDS 设计提供指南。然后讨论 NDDS 在临床应用中的几个现有挑战和进一步机遇。本综述旨在为通过减轻有效肿瘤治疗的生物障碍来优化 NDDS 设计提供指南。然后讨论 NDDS 在临床应用中的几个现有挑战和进一步机遇。本综述旨在为通过减轻有效肿瘤治疗的生物障碍来优化 NDDS 设计提供指南。