2. Academic Validation
  3. High-efficiency engineering of cell membrane nanovesicles with intrinsic homotypic targeting for precision cancer drug delivery

High-efficiency engineering of cell membrane nanovesicles with intrinsic homotypic targeting for precision cancer drug delivery

  • Int J Biol Macromol. 2025 Dec;334(Pt 1):148793. doi: 10.1016/j.ijbiomac.2025.148793.
Thi-Luu Ho 1,  Thi Thuy Tien Phan 2,  I-Lin Tsai 3,  Tran Quoc Dung Huynh 4,  Yao-An Shen 5,  Yu-Jui Fan 6
Affiliations

Affiliations

  • 1 International Ph.D. Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei, 110301, Taiwan; Institute of Pharmaceutical Education and Research, Binh Duong University, Thu Dau Mot, 820000, Binh Duong, Viet Nam.
  • 2 Institute of Pharmaceutical Education and Research, Binh Duong University, Thu Dau Mot, 820000, Binh Duong, Viet Nam; Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, 110301, Taiwan.
  • 3 Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110301, Taiwan.
  • 4 Institute of Pharmaceutical Education and Research, Binh Duong University, Thu Dau Mot, 820000, Binh Duong, Viet Nam; Institute of Biological Chemistry, Academia Sinica, Taipei, 115201, Taiwan.
  • 5 International Ph.D. Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei, 110301, Taiwan; Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110301, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, 110301, Taiwan; International Master/Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, 110301, Taiwan. Electronic address: [email protected].
  • 6 International Ph.D. Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei, 110301, Taiwan; National Yang Ming Chiao Tung University, Department of Mechanical Engineering, Hsinchu, 300093, Taiwan. Electronic address: [email protected].
PMID: 41213369 DOI: 10.1016/j.ijbiomac.2025.148793
Abstract

Cell membrane-derived nanovesicles (NVs; CM-NVs) have emerged as a promising next-generation platform for targeted drug delivery in Cancer therapy, owing to their intrinsic biocompatibility and ability to present native surface proteins. These features enable homotypic targeting for donor tumor cells while minimizing off-target effects and immune activation. Despite their potential, low yields and technical complexity of conventional methods for producing CM-NVs limit their broader clinical application. In this study, we applied a rapid polymerization-based approach for generating CM-NVs, which produced yields up to 12-fold higher than native extracellular vesicle (EV) isolation and 6-fold greater than the blebbing-based method. Proteomic data indicated that origin cells passed down a distinct molecular fingerprint to the polymerized (p)NVs. Moreover, the resulting pNVs demonstrated robust specificity for donor Cancer cells, including parental cells and Cancer stem cell populations, and exhibited superior biocompatibility and non-tumorigenic transformation. Taken together, these findings highlight the polymerization method as an effective strategy for producing functional cell membrane vesicles, supporting their potential as next-generation carriers for EV-based Cancer therapeutics.

Keywords

Cell membrane-derived nanovesicle; Drug delivery; Extracellular vesicle; cancer stem cell.

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