2. Academic Validation
  3. Membrane Fusion Drives Facile Uptake of Cell Membrane-Coated Nanocarriers

Membrane Fusion Drives Facile Uptake of Cell Membrane-Coated Nanocarriers

  • ACS Nano. 2025 Jul 1;19(25):23001-23010. doi: 10.1021/acsnano.5c02888.
Jingyi Qiu 1 2,  Shuai Gong 2 3,  Yasin Alp 2 3,  Jewel Medeiros 2 3,  Emily Agnello 2 4,  S Thayumanavan 1 2 3
Affiliations

Affiliations

  • 1 Department of Biomedical Engineering, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States.
  • 2 Center for Bioactive Delivery, Institute for Applied Life Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States.
  • 3 Department of Chemistry, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States.
  • 4 Department of Polymer Science and Engineering, University of Massachusetts, Amherst, Massachusetts 01003, United States.
PMID: 40522898 DOI: 10.1021/acsnano.5c02888
Abstract

Endocytosis has been the bane of the intracellular delivery efficiency of nanoscale systems. A class of delivery systems, viz., cell membrane-coated nanoparticles (CMNPs), show efficacious and even cell-selective uptake. We were interested in investigating the mechanism of interaction between cells and CMNPs, especially in the context of endocytic uptake and endosomal escape. We find that CMNPs are mainly taken up through a membrane-fusion-driven uptake pathway, bypassing endosomal entrapment and directly delivering therapeutic cargo to the cytoplasm. This fusion mechanism results in a significant enhancement in the intracellular delivery efficiency of both hydrophobic small molecules and nucleic acids as the cargo. The cargo-agnostic increase in delivery efficacy suggests a broad impact of this delivery system in diverse therapeutic areas.

Keywords

cell membrane coated nanoparticle; chemotherapeutic; gene delivery; homotypic targeting; lipid miscibility; membrane fusion.

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