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  3. Synergistic mechanical and therapeutic modulation of engineered tumor cell-derived microparticles for enhanced cancer treatment

Synergistic mechanical and therapeutic modulation of engineered tumor cell-derived microparticles for enhanced cancer treatment

  • Cell Rep Med. 2026 Feb 17;7(2):102591. doi: 10.1016/j.xcrm.2026.102591.
Xiaojuan Zhang 1,  Ke Zhang 1,  Yinmei Zhu 1,  Shiyi Xu 1,  Shiyu Li 1,  Haojie Liu 1,  Weilin Lv 1,  Zixiang Xie 1,  Yizhou Huang 1,  Xin Li 1,  Nana Bie 1,  Sheng Wang 1,  Zhao Huang 2,  Hongmei Zheng 3,  Chuan Qin 4,  Xiangliang Yang 5,  Lu Gan 6,  Tuying Yong 7
Affiliations

Affiliations

  • 1 National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
  • 2 Division of Hepato-Pancreato-Biliary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Breast Cancer Center, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, China.
  • 4 Department of Neurology, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 5 National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Huazhong University of Science and Technology, Wuhan 430074, China; Hubei Bioinformatics and Molecular Imaging Key Laboratory, Huazhong University of Science and Technology, Wuhan 430074, China. Electronic address: [email protected].
  • 6 National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Huazhong University of Science and Technology, Wuhan 430074, China; Hubei Bioinformatics and Molecular Imaging Key Laboratory, Huazhong University of Science and Technology, Wuhan 430074, China. Electronic address: [email protected].
  • 7 National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Huazhong University of Science and Technology, Wuhan 430074, China; Hubei Bioinformatics and Molecular Imaging Key Laboratory, Huazhong University of Science and Technology, Wuhan 430074, China. Electronic address: [email protected].
PMID: 41666924 DOI: 10.1016/j.xcrm.2026.102591
Abstract

Cancer Stem Cells (CSCs) and circulating tumor cells (CTCs) are pivotal contributors to tumor progression, metastasis, and therapeutic resistance. However, their effective eradication remains a significant hurdle in Cancer treatments. Here, we report a mechanically optimized drug delivery platform based on ginsenoside Rh2-engineered tumor cell-derived microparticles (MP) loaded with doxorubicin (D@RM) for targeted elimination of CSCs and CTCs. Rh2 incorporation into MP modulates membrane lipid composition and disrupts lipid raft integrity, significantly reducing particle stiffness and enhancing deformability. These biomechanical changes promote tumor accumulation, deep tissue penetration, and clathrin-mediated uptake by CSCs. Concurrently, Rh2 suppresses drug efflux and stemness pathways, synergistically enhancing doxorubicin cytotoxicity toward CSCs. Moreover, D@RM efficiently bind and neutralize CTCs in circulation, thereby inhibiting metastatic dissemination. This study presents a versatile and translational strategy that integrates membrane mechanics and pharmacological modulation to improve the precision and efficacy of nanomedicine in Cancer therapy.

Keywords

cancer stem cells; circulating tumor cells; deep tumor penetration; ginsenoside Rh2; mechanical modulation; microparticles; softness; tumor accumulation; tumor metastasis.

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