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A modular approach to enhancing cell membrane-coated nanoparticle functionality using genetic engineering.

Nishta Krishnan1, Yao Jiang1, Jiarong Zhou1

  • 1Department of NanoEngineering, Chemical Engineering Program, and Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.

Nature Nanotechnology
|October 31, 2023
PubMed
Summary
This summary is machine-generated.

This study presents a genetic engineering method to create advanced cell membrane-coated nanoparticles (CNPs). These functionalized CNPs show improved targeting and therapeutic effects in cancer models.

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Molecular Biology

Background:

  • Cell membrane-coated nanoparticles (CNPs) are versatile biomedical tools.
  • Enhancing CNP functionality is crucial for advanced applications.
  • Existing methods for CNP functionalization can be limiting.

Purpose of the Study:

  • To develop a modular genetic engineering approach for functionalizing CNPs.
  • To demonstrate the broad applicability of this technique using diverse targeting ligands.
  • To evaluate the in vitro and in vivo efficacy of the engineered CNPs.

Main Methods:

  • Engineered cell membranes to express SpyCatcher for covalent ligand attachment via SpyTag.
  • Created three distinct CNP formulations using designed ankyrin repeat proteins, affibodies, and single-chain variable fragments.
  • Tested nanoparticle affinity in vitro and therapeutic efficacy in a murine ovarian cancer xenograft model with a chemotherapeutic payload.

Main Results:

  • Modified CNPs demonstrated enhanced binding to target cells overexpressing cognate receptors.
  • Formulated CNPs effectively targeted tumors and suppressed growth in vivo.
  • The genetic engineering approach proved feasible for creating multifunctional CNPs.

Conclusions:

  • Genetic engineering provides a powerful and flexible platform for developing advanced, multifunctional CNPs.
  • This modular strategy accelerates the creation of targeted nanoparticles for diverse biomedical applications.
  • The engineered CNPs show significant potential for cancer therapy and other therapeutic interventions.