CCR2-overexpressing biomimetic carrier-free nanoplatform for enhanced cascade ferroptosis tumor therapy

作者：Zhang, Xinyu; Xu, Xueli; Liu, Huimin; Ni, Nengyi; Liu, Shuangqing; Gong, Yufang; Ma, Guiqi; Song, Linlin; Meng, Qingwei^*; Fan, Qing^*; Sun, Xiao^*

来源：Acta Biomaterialia, 2023, 166: 604-614.

DOI：10.1016/j.actbio.2023.05.006

• Ferroptosis
• Carrier-free
• Biomimetic
• Drug release
• Cascade therapy

Ferroptosis-based nanoplatforms have shown great potential in cancer therapy. However, they also face issues such as degradation and metabolism. Carrier-free nanoplatforms consisting of active drugs can effectively avoid the security issues associated with additional carrier ingredients. Herein, a biomimetic carrier-free nanoplatform (HESN@CM) was designed to treat cancer by modulating cascade metabolic pathways of ferroptosis. CCR2-overexpressing macrophage membrane-modified HESN can target cancer cells via the CCR2-CCL2 axis. The acidic tumor microenvironment (TME) can disrupt the supramolecular interaction of HESN, releasing hemin and erastin. Then, erastin could induce cancer cells ferroptosis by inhibiting system X-C - pathways, while hemin, a vital component of blood to transport oxygen, could be broken down by heme oxygenase-1 (HO-1), increasing the intracellular Fe2+ concentration to induce cancer cells' ferroptosis further. Meanwhile, erastin could enhance the activity of HO-1, further promoting the release of Fe2+ from hemin. As a result, HESN@CM demonstrated superior therapeutic efficacy in both primary and metastatic tumors in vitro and in vivo . The carrier-free HESN@CM provided cascade ferroptosis tumor therapy strategies for potential clinical application.

• 单位
  哈尔滨医科大学; 山东省医学科学院