铁蛋白具有稳定的均一空心结构，以及靶向肿瘤和优异的生物相容性，使其成为一种有前途的药物传递载体。然而，当前的铁蛋白药物装载策略涉及复杂的步骤和严酷的反应条件，导致药物装载产率和回收率低，限制了铁蛋白纳米药物的临床应用前景。在本研究中，我们利用E螺旋剪切铁蛋白突变体（Ecut-HFn）的高效热敏性和Cu2+的协助，在低温下实现了一步法中抗肿瘤药物的高效装载。该方法具有温和的反应条件（45℃），高装载效率（约110个多柔比星（Dox）/Ecut-HFn），以及较高的蛋白质和Dox回收率（蛋白质回收率约94%，Dox回收率高达45%）。制备的铁蛋白-Dox颗粒（Ecut-HFn-Cu-Dox）具有均匀的大小分布、良好的稳定性，并保留了铁蛋白的天然肿瘤靶向能力。总的来说，这种利用热敏性铁蛋白突变体进行温控药物装载的策略省能、环保、高效且易操作，为扩大铁蛋白药物载体的工业生产提供了新的视角。版权所有 © 2023 Elsevier B.V. 发表。

Ferritin possesses a stable and uniform cage structure, along with tumor-targeting properties and excellent biocompatibility, making it a promising drug delivery vehicle. However, the current ferritin drug loading strategy involves complex steps and harsh reaction conditions, resulting in low yield and recovery of drug loading, which limits the clinical application prospects of ferritin nanomedicine. In this study, we utilized the high-efficiency heat-sensitivity of the multiple channel switch structures of the E-helix-cut ferritin mutant (Ecut-HFn) and Cu2+ assistance to achieve high-efficiency loading of chemotherapeutic drugs in a one-step process at low temperatures. This method features mild reaction conditions (45 °C), high loading efficiency (about 110 doxorubicin (Dox) per Ecut-HFn), and improved protein and Dox recovery rates (with protein recovery rate around 94 % and Dox recovery rate reaching up to 45 %). The prepared ferritin-Dox particles (Ecut-HFn-Cu-Dox) exhibit a uniform size distribution, good stability, and retain the natural tumor targeting ability of ferritin. Overall, this temperature-controlled drug loading strategy utilizing heat-sensitivity ferritin mutants is energy-saving, environmentally friendly, efficient, and easy to operate, offering a new perspective for scaling up the industrial production of ferritin drug carriers.Copyright © 2023. Published by Elsevier B.V.