Abstract：
Nutrient avidity is one of the most distinctive features of tumours. However, nutrient deprivation has yielded limited clinical benefits. In Gaucher disease, an inherited metabolic disorder, cells produce cholesteryl-glucoside which accumulates in lysosomes and causes cell damage. Here we develop a nanoparticle (AbCholB) to emulate natural-lipoprotein-carried cholesterol and initiate Gaucher disease-like damage in cancer cells. AbCholB is composed of a phenylboronic-acid-modified cholesterol (CholB) and albumin. Cancer cells uptake the nanoparticles into lysosomes, where CholB reacts with glucose and generates a cholesteryl-glucoside-like structure that resists degradation and aggregates into microscale crystals, causing Gaucher disease-like damage in a glucose-dependent manner. In addition, the nutrient-sensing function of mTOR is suppressed. It is observed that normal cells escape severe damage due to their inferior ability to compete for nutrients compared with cancer cells. This work provides a bioinspired strategy to selectively impede the metabolic action of cancer cells by taking advantage of their nutrient avidity.
摘要：
营养亲和力是肿瘤最显著的特征之一。然而,营养剥夺产生了有限的临床益处。在戈谢病中，遗传性代谢紊乱,细胞产生胆固醇-葡萄糖苷，其在溶酶体中积累并导致细胞损伤。在这里，我们开发了一种纳米颗粒（AbCholB）来模拟天然脂蛋白携带的胆固醇，并在癌细胞中引发戈谢病样损伤。AbCholB由苯基硼酸修饰的胆固醇(CholB)和白蛋白组成。癌细胞将纳米颗粒吸收到溶酶体中，其中CholB与葡萄糖反应并产生胆固醇基-葡糖苷样结构，抵抗降解并聚集成微米级晶体，以葡萄糖依赖性方式引起戈谢病样损伤。此外,mTOR的营养感知功能被抑制。观察到正常细胞由于其与癌细胞相比竞争营养的能力较差而逃避了严重的损害。这项工作提供了一种生物启发策略，通过利用其营养亲和力来选择性地阻止癌细胞的代谢作用。
