Delivering cancer therapeutics to tumors necessitates their escape from the surrounding blood vessels. Tumor vasculatures are not always sufficiently leaky. Herein, we engineer therapeutically competent leakage of therapeutics from tumor vasculature with gold nanoparticles capable of inducing endothelial leakiness (NanoEL). These NanoEL gold nanoparticles activated the loss of endothelial adherens junctions without any perceivable toxicity to the endothelial cells. Microscopically, through real time live animal intravital imaging, we show that NanoEL particles induced leakiness in the tumor vessels walls and improved infiltration into the interstitial space within the tumor. In both primary tumor and secondary micrometastases animal models, we show that pretreatment of tumor vasculature with NanoEL particles before therapeutics administration could completely regress the cancer. Engineering tumoral vasculature leakiness represents a new paradigm in our approach towards increasing tumoral accessibility of anti-cancer therapeutics instead of further increasing their anti-cancer lethality.

向肿瘤提供癌症治疗需要它们逃离周围的血管。肿瘤脉管系统并不总是有足够的渗漏。在此，我们利用能够诱导内皮渗漏的金纳米颗粒（NanoEL）设计了具有治疗能力的治疗药物从肿瘤脉管系统的渗漏。这些 NanoEL 金纳米粒子激活了内皮粘附连接的损失，而对内皮细胞没有任何可察觉的毒性。在显微镜下，通过实时活体动物活体成像，我们发现 NanoEL 颗粒可诱导肿瘤血管壁渗漏，并改善肿瘤内间隙的浸润。在原发性肿瘤和继发性微转移动物模型中，我们表明在给予治疗之前用 NanoEL 颗粒预处理肿瘤脉管系统可以完全消退癌症。工程肿瘤脉管系统渗漏代表了我们增加抗癌治疗的肿瘤可及性而不是进一步增加其抗癌致死率的方法的新范例。