2. Academic Validation
  3. CCR2-overexpressing Biomimetic Carrier-free Nanoplatform for Enhanced Cascade Ferroptosis Tumor Therapy

CCR2-overexpressing Biomimetic Carrier-free Nanoplatform for Enhanced Cascade Ferroptosis Tumor Therapy

  • Acta Biomater. 2023 May 6;S1742-7061(23)00249-0. doi: 10.1016/j.actbio.2023.05.006.
Xinyu Zhang 1,  Xueli Xu 2,  Huimin Liu 2,  Nengyi Ni 3,  Shuangqing Liu 1,  Yufang Gong 1,  Guiqi Ma 2,  Linlin Song 2,  Qing Fan 4,  Qingwei Meng 5,  Xiao Sun 6
Affiliations

Affiliations

  • 1 Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China.
  • 2 Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, China.
  • 3 Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117585, Singapore.
  • 4 Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, China. Electronic address: [email protected].
  • 5 Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China. Electronic address: [email protected].
  • 6 Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, China. Electronic address: [email protected].
PMID: 37156432 DOI: 10.1016/j.actbio.2023.05.006
Abstract

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 XC- 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. STATEMENT OF SIGNIFICANCE: CCR2-overexpressing biomimetic carrier-free nanoplatform (HESN@CM) was designed for Cancer treatment by modulating metabolic pathways of Ferroptosis. HESN modified with CCR2-overexpressing macrophage membrane can target tumor cells via the CCR2-CCL2 axis. HESN was composed of hemin and erastin without additional vectors. Erastin could directly induce Ferroptosis, while hemin could be broken down by heme oxygenase-1 (HO-1), increasing the intracellular Fe2+ concentration to enhance Ferroptosis further. Meanwhile, erastin could improve the activity of HO-1, promoting the release of Fe2+ from hemin. Therefore, HESN@CM with good bioavailability, stability, and simple preparation can realize cascade Ferroptosis tumor therapy and have the potential prospect of clinical translation.

Keywords

biomimetic; carrier-free; cascade therapy; drug release; ferroptosis.

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