Effective tumor vessel barrier disruption mediated by perfluoro-N-(4-methylcyclohexyl) piperidine nanoparticles to enhance the efficacy of photodynamic therapy
Effective tumor vessel barrier disruption mediated by perfluoro-N-(4-methylcyclohexyl) piperidine nanoparticles to enhance the efficacy of photodynamic therapy
复制标题
全氟-N-(4-甲基环己基)哌啶纳米粒子介导的有效肿瘤血管屏障破坏可增强光动力疗法的疗效
DOI：
10.1039/d1nr02880d
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发表时间：
2021
期刊：
影响因子：
6.7
通讯作者：
Zhou Zaigang
中科院分区：
文献类型：
--
作者：
Xiong Wei;Qi Lin;Si Deli;Jiang Xin;Liu Yu;Zheng Chunjuan;Li Yuan;Shen Jianliang;Zhou Zaigang
背景：目前，肿瘤药物渗透受限、氧灌注不良和免疫抑制微环境是显着降低光动力疗法（PDT）疗效的最重要瓶颈。这些主要瓶颈的主要原因是血小板活化维持异常的肿瘤血管屏障。因此，血小板抑制可能提供一种最有效增强PDT疗效的新方法。然而，据我们所知，很少有研究验证这种方法在体内和体外增强 PDT 疗效的有效性。本研究发现全氟-N-(4-甲基环己基)哌啶负载白蛋白(PMP@Alb)纳米颗粒具有优异的血小板抑制能力。 PMP@Alb 治疗后，由于肿瘤血管屏障被破坏，可以观察到肿瘤内药物积累、氧灌注和 T 细胞浸润显着增强。此外，PMP@Alb 纳米粒子显着放大了 ICG@Lip 介导的 PDT 效果。事实证明，PMP@Alb 可作为一种有用的工具，通过有效的血小板抑制来破坏肿瘤血管屏障，从而提高现有 PDT 的疗效。
Background: Currently, limited tumor drug permeation, poor oxygen perfusion and immunosuppressive microenvironments are the most important bottlenecks that significantly reduce the efficacy of photodynamic therapy (PDT). The main cause of these major bottlenecks is the platelet activation maintained abnormal tumor vessel barriers. Thus, platelet inhibition may present a new way to most effectively enhance the efficacy of PDT. However, to the best of our knowledge, few studies have validated the effectiveness of such a way in enhancing the efficacy of PDT both in vivo and in vitro. In this study, perfluoro-N-(4-methylcyclohexyl) piperidine-loaded albumin (PMP@Alb) nanoparticles were discovered, which possess excellent platelet inhibition ability. After PMP@Alb treatment, remarkably enhanced intra-tumoral drug accumulation, oxygen perfusion and T cell infiltration could be observed owing to the disrupted tumor vessel barriers. Besides, the effect of ICG@Lip mediated PDT was significantly amplified by PMP@Alb nanoparticles. It was demonstrated that PMP@Alb could be used as a useful tool to improve the efficacy of existing PDT by disrupting tumor vessel barriers through effective platelet inhibition.