Perfluorocarbon Nanoparticles Mediated Platelet Blocking Disrupt Vascular Barriers to Improve the Efficacy of Oxygen‐Sensitive Antitumor Drugs

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. Perfluorotributylamine‐based albumin nanoparticles (PFTBA@HSA), a novel platelet function inhibitor, is successfully developed to break platelets maintaining tumor vessel barriers, leading to significantly enhanced drug delivery and oxygen perfusion without causing any side effects. Therefore, PFTBA@HSA could be used as a novel method to amplify the efficacy of antitumor drugs, especially oxygen‐sensitive drugs.