Nanoparticle delivery to solid tumours over the past ten years has stagnated at a median of 0.7% of the injected dose. Varying nanoparticle designs and strategies have yielded only minor improvements. Here we discovered a dose threshold for improving nanoparticle tumour delivery: 1 trillion nanoparticles in mice. Doses above this threshold overwhelmed Kupffer cell uptake rates, nonlinearly decreased liver clearance, prolonged circulation and increased nanoparticle tumour delivery. This enabled up to 12% tumour delivery efficiency and delivery to 93% of cells in tumours, and also improved the therapeutic efficacy of Caelyx/Doxil. This threshold was robust across different nanoparticle types, tumour models and studies across ten years of the literature. Our results have implications for human translation and highlight a simple, but powerful, principle for designing nanoparticle cancer treatments.

在过去十年中，纳米颗粒向实体瘤的输送停滞在注射剂量的0.7％的中值。各种纳米颗粒的设计和策略仅产生了很小的改进。在这里，我们发现了改善纳米颗粒肿瘤递送的剂量阈值：小鼠中有1万亿个纳米颗粒。高于此阈值的剂量会使库普弗细胞的吸收速率不堪重负，肝脏清除率非线性降低，循环时间延长，纳米颗粒肿瘤递送增加。这使得高达12％的肿瘤递送效率和93％的肿瘤细胞递送成为可能，并且还提高了Caelyx / Doxil的治疗效果。该阈值在不同的纳米颗粒类型，肿瘤模型和十年的文献研究中均很可靠。我们的结果对人工翻译具有影响，并强调了一个简单但功能强大的