Zhang Jian, Pan Tony, Lee Jimmy, Goldberg Sanja, King Sarah Ann, Tang Erting, Hu Yifei, Chen Lifeng, Hoover Alex, Zhu Linyong, Eng Oliver S, Dekel Benjamin, Huang Jun, Wu Xiaoyang
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA; Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Pritzker School of Molecular Engineering, The University of Chicago, Chicago, IL 60637, USA.
Cell Rep Med. 2025 Jan 21;6(1):101920. doi: 10.1016/j.xcrm.2024.101920. Epub 2025 Jan 13.
Metabolic reprogramming of tumor cells is an emerging hallmark of cancer. Among all the changes in cancer metabolism, increased glucose uptake and the accumulation of lactate under normoxic conditions (the "Warburg effect") is a common feature of cancer cells. In this study, we develop a lactate-responsive drug delivery platform by targeting the Warburg effect. We design and test a gold/mesoporous silica Janus nanoparticle system as a gated drug carrier, in which the gold particles are functionalized with lactate oxidase and the silica particles are capped with α-cyclodextrin through surface arylboronate modification. In the presence of lactate, the lactate oxidase generates hydrogen peroxide, which induces the self-immolation reaction of arylboronate, leading to uncapping and drug release. Our results demonstrate greatly improved drug delivery specificity and therapeutic efficacy with this platform for the treatment of different cancers. Our findings present an effective approach for drug delivery by metabolic targeting of tumors.
肿瘤细胞的代谢重编程是癌症一个新出现的标志。在癌症代谢的所有变化中，在常氧条件下葡萄糖摄取增加和乳酸积累（“瓦伯格效应”）是癌细胞的一个共同特征。在本研究中，我们通过靶向瓦伯格效应开发了一种乳酸响应型药物递送平台。我们设计并测试了一种金/介孔二氧化硅 Janus 纳米颗粒系统作为门控药物载体，其中金颗粒用乳酸氧化酶功能化，二氧化硅颗粒通过表面芳基硼酸酯修饰用α-环糊精封端。在乳酸存在的情况下，乳酸氧化酶产生过氧化氢，过氧化氢诱导芳基硼酸酯的自焚反应，导致封端解除和药物释放。我们的结果表明，该平台在治疗不同癌症时具有大大提高的药物递送特异性和治疗效果。我们的发现为通过肿瘤的代谢靶向进行药物递送提供了一种有效方法。
