2. Academic Validation
  3. Anti-phagocytosis-blocking repolarization-resistant membrane-fusogenic liposome (ARMFUL) for adoptive cell immunotherapy

Anti-phagocytosis-blocking repolarization-resistant membrane-fusogenic liposome (ARMFUL) for adoptive cell immunotherapy

  • Sci Adv. 2023 Aug 9;9(32):eadh2413. doi: 10.1126/sciadv.adh2413.
Chunxiong Zheng 1,  Qingguo Zhong 1,  Ke Yi 1,  Huimin Kong 1,  Fangfang Cao 2 3 4,  Chenya Zhuo 1,  Yanteng Xu 1,  Run Shi 5,  Enguo Ju 1,  Wantong Song 6,  Yu Tao 1,  Xiaoyuan Chen 2 3 4 7,  Mingqiang Li 1
Affiliations

Affiliations

  • 1 Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
  • 2 Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore 117597, Singapore.
  • 3 Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore.
  • 4 Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
  • 5 Department of Oncology, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
  • 6 Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
  • 7 Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
PMID: 37556535 DOI: 10.1126/sciadv.adh2413
Abstract

Equipping multiple functionalities on adoptive effector cells is essential to overcome the complex immunological barriers in solid tumors for superior antitumor efficacy. However, current cell engineering technologies cannot endow these functionalities to cells within a single step because of the different spatial distributions of targets in one cell. Here, we present a core-shell anti-phagocytosis-blocking repolarization-resistant membrane-fusogenic Liposome (ARMFUL) to achieve one-step multiplexing cell engineering for multifunctional cell construction. Through fusing with the M1 macrophage membrane, ARMFUL inserts an anti-CD47 (aCD47)-modified lipid shell onto the surface and simultaneously delivers colony-stimulating factor 1 receptor inhibitor BLZ945-loaded core into the cytoplasm. The surface-presenting aCD47 boosts macrophage's phagocytosis against the tumor by blocking CD47. The cytoplasm-located BLZ945 prompts its polarization resistance to M2 phenotype in the immunosuppressive microenvironment via inactivating the intracellular M2 polarization signaling pathway. This ARMFUL provides a versatile cell engineering platform to customize multimodal cellular functions for enhanced adoptive cell therapy.

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