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<p>Functionalization of hydrophobic nanoparticles for biomedical applications requires water dispersibility, colloidal stability, and tunable surface chemistry for biomolecule conjugation. While phospholipid-polyethylene glycol (PEG) coating has been employed for nanoparticle functionalization, systematic protocols for controlling functional group density and comprehensive characterization of the coating mechanism remain lacking. Here we present a detailed protocol and theoretical framework for tunable functionalization using 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)] (DSPE-PEG) derivatives. We validated these experimentally using iron oxide nanoparticles as a model system. Functional group density can be precisely controlled from 0% to 100% by adjusting the mixing ratio of functionalized to non-functionalized DSPE-PEG without changing the coating procedure. Critically, we provide step-by-step protocols with troubleshooting strategies for each process stage, enabling reproducible implementation across different laboratories. This combination of mechanistic understanding and practical guidance provides an immediately accessible foundation for researchers developing nanoparticle platforms for targeted delivery, cell isolation, and multimodal imaging.</p>

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Self-assembled micellization of nanoparticles for tunable functionalization by phospholipid-polyethylene glycol

  • 期刊论文

  • 发表日期：

    2026年5月26日

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  • Da-Hye Ryu,
  • Dong-Hyun You,
  • Myung Kyung Jung,
  • Ji-Soo Lee,
  • So-Hee Park,
  • Yiseul Ryu,
  • Joong-jae Lee,
  • Seong-Min Jo

摘要

Functionalization of hydrophobic nanoparticles for biomedical applications requires water dispersibility, colloidal stability, and tunable surface chemistry for biomolecule conjugation. While phospholipid-polyethylene glycol (PEG) coating has been employed for nanoparticle functionalization, systematic protocols for controlling functional group density and comprehensive characterization of the coating mechanism remain lacking. Here we present a detailed protocol and theoretical framework for tunable functionalization using 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)] (DSPE-PEG) derivatives. We validated these experimentally using iron oxide nanoparticles as a model system. Functional group density can be precisely controlled from 0% to 100% by adjusting the mixing ratio of functionalized to non-functionalized DSPE-PEG without changing the coating procedure. Critically, we provide step-by-step protocols with troubleshooting strategies for each process stage, enabling reproducible implementation across different laboratories. This combination of mechanistic understanding and practical guidance provides an immediately accessible foundation for researchers developing nanoparticle platforms for targeted delivery, cell isolation, and multimodal imaging.