State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University and School of Life Sciences, Nanjing University, Nanjing, 210093, China.
Institute of Drug R&D, Nanjing University, Nanjing, 210093, China.
Small. 2018 Nov;14(45):e1801694. doi: 10.1002/smll.201801694. Epub 2018 Oct 11.
Currently, limited tumor drug permeation and poor oxygen perfusion are two major bottlenecks that significantly impair the efficacy of existing antitumor drugs, especially oxygen-sensitive antitumor drugs. One vital cause of these major bottlenecks is the abnormal tumor vessel barrier. To the best knowledge of the authors, platelets play a vital role in the maintenance of an abnormal tumor blood barrier through platelet-tumor interaction. Thus, platelet inhibition may present a new way to enhance drug delivery. In this study, it is originally discovered that perfluorotributylamine-based albumin nanoparticles (PFTBA@HSA) possess excellent platelet inhibiting abilities, which then selectively disrupt the tumor vessel barrier, resulting in a remarkably enhanced intratumoral drug accumulation. Interestingly enough, the tumor hypoxia is also obviously relieved by enhanced oxygen carrier red blood cell distribution and PFTBA@HSA infiltration in the tumors. Finally, the efficacy of oxygen-sensitive antitumor drugs is significantly amplified by PFTBA@HSA owing to enhanced drug permeation and relieved tumor hypoxia. Therefore, for the first time, it is demonstrated that PFTBA@HSA could be used as an effective way to improve the efficacy of existing tumor therapies by disrupting tumor vessel barriers through targeted platelet inhibition.
目前，有限的肿瘤药物渗透和较差的氧气灌注是显著降低现有抗肿瘤药物（尤其是氧敏感抗肿瘤药物）疗效的两个主要瓶颈。这些主要瓶颈的一个重要原因是异常的肿瘤血管屏障。据作者所知，血小板通过血小板-肿瘤相互作用在维持异常肿瘤血液屏障中起着至关重要的作用。因此，血小板抑制可能为增强药物输送提供一种新方法。在这项研究中，最初发现基于全氟三丁胺的白蛋白纳米粒子（PFTBA@HSA）具有优异的血小板抑制能力，然后选择性地破坏肿瘤血管屏障，导致肿瘤内药物蓄积显著增加。有趣的是，通过增强氧载体红细胞的分布和 PFTBA@HSA 在肿瘤中的渗透，肿瘤缺氧也明显得到缓解。最后，由于药物渗透增强和肿瘤缺氧缓解，PFTBA@HSA 显著放大了氧敏感抗肿瘤药物的疗效。因此，首次证明 PFTBA@HSA 可以通过靶向血小板抑制破坏肿瘤血管屏障，作为提高现有肿瘤治疗效果的有效方法。
