Overcoming key biological barriers to cancer drug delivery and efficacy.
Overcoming key biological barriers to cancer drug delivery and efficacy.
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DOI：
10.1016/j.jconrel.2017.09.016
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发表时间：
2017-12-10
期刊：
影响因子：
--
通讯作者：
Schnitzer JE
中科院分区：
文献类型：
--
作者：
Kim SM;Faix PH;Schnitzer JE
递送效率低下继续阻碍癌症疗法的有效性，这些疗法旨在使用不同的策略（例如纳米载体、靶向剂以及针对特定基因突变的匹配治疗）来破坏实体瘤。所有当代的全身抗癌药物都依赖于被动经血管机制来递送至实体瘤中。通过主动递送策略可以显着提高我们当前药物库的治疗效果。在这里，我们讨论血管内皮细胞层呈现的屏障和肿瘤血管的异常性质如何极大地阻碍药物输送和治疗效果。我们描述了分子穿过正常组织和实体瘤中的内皮细胞（EC）屏障的机制，包括实现被动或主动运输的细胞旁和跨细胞途径。我们还讨论了导致实体瘤难以治疗的药物输送的具体障碍，以及克服这些障碍和增强药物渗透的策略。最后，我们描述了小凹泵送系统，这是一种有前途的主动运输替代品，可以替代被动药物输送穿过内皮细胞屏障。每种策略都需要进一步测试来确定其治疗适用性和临床效用。
Poor delivery efficiency continues to hamper the effectiveness of cancer therapeutics engineered to destroy solid tumors using different strategies such as nanocarriers, targeting agents, and matching treatments to specific genetic mutations. All contemporary systemic anti-cancer agents are dependent upon passive transvascular mechanisms for their delivery into solid tumors. The therapeutic efficacies of our current drug arsenal could be significantly improved with an active delivery strategy. Here, we discuss how drug delivery and therapeutic efficacy are greatly hindered by barriers presented by the vascular endothelial cell layer and by the aberrant nature of tumor blood vessels in general. We describe mechanisms by which molecules cross endothelial cell (EC) barriers in normal tissues and in solid tumors, including paracellular and transcellular pathways that enable passive or active transport. We also discuss specific obstacles to drug delivery that make solid tumors difficult to treat, as well strategies to overcome them and enhance drug penetration. Finally, we describe the caveolae pumping system, a promising active transport alternative to passive drug delivery across the endothelial cell barrier. Each strategy requires further testing to define its therapeutic applicability and clinical utilities.
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DOI：
10.1073/pnas.76.12.6439
发表时间：
1979-01-01
影响因子：
11.1
作者：
BUNDGAARD, M;FROKJAERJENSEN, J;CRONE, C
通讯作者：
CRONE, C
影响因子：
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影响因子：
8
作者：
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通讯作者：
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影响因子：
5.4
作者：
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通讯作者：
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影响因子：
7.8
作者：
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通讯作者：
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