Biomimetic Surface-Enhanced Raman Scattering Nanoparticles with Improved Dispersibility, Signal Brightness, and Tumor Targeting Functions

Indrajit Srivastava, Ruiyang Xue, Jamie Jones, Hyunjoon Rhee, Kristen Flatt, Viktor Gruev, Shuming Nie

Research output: Contribution to journalArticlepeer-review


The development of biocompatible and nontoxic surface-enhanced Raman scattering (SERS) nanoparticles is of considerable current interest because of their attractive biomedical applications such as ultrasensitive in vitro diagnostics, in vivo tumor imaging, and spectroscopy-guided cancer surgery. However, current SERS nanoparticles are prepared and stored in aqueous solution, have limited stability and dispersibility, and are not suitable for lyophilization and storage by freeze-drying or other means. Here, we report a simple but robust method to coat colloidal SERS nanoparticles by naturally derived biomimetic red blood cell membranes (RBCM), leading to a dramatic improvement in stability and dispersibility under freeze-thawing, lyophilization, heating, and physiological conditions. The results demonstrate that the lyophilized SERS nanoparticles in the solid form can be readily dissolved and dispersed in physiological buffer solutions. A surprising finding is that the RBCM-coated SERS particles are considerably brighter (by as much as 5-fold) than PEGylated SERS particles under similar experimental conditions. This additional enhancement is believed to arise from the hydrophobic nature of RBCM's hydrocarbon chains, which is known to reduce electronic dampening and boost electromagnetic field enhancement. A further advantage in using biomimetic membrane coatings is that the bilayer membrane structure allows nonvalent insertion of molecular ligands for tumor targeting. In particular, we show that cyclic-RGD, a tumor-targeting peptide, can be efficiently inserted into the membrane coatings of SERS nanoparticles for targeting the ανβ3 integrin receptors expressed on cancer cells. Thus, biomimetic RBCMs provide major advantages over traditional polyethylene glycols for preparing SERS nanoparticles with improved dispersibility, higher signal intensity, and more efficient biofunctionalization.

Original languageEnglish (US)
Pages (from-to)8051–8063
JournalACS Nano
Issue number5
Early online dateApr 26 2022
StatePublished - May 24 2022


  • dispersion stability
  • gold nanoparticles
  • plasmonics
  • red blood cell membrane
  • surface coatings
  • surface-enhanced Raman scattering
  • tumor targeting

ASJC Scopus subject areas

  • General Materials Science
  • General Engineering
  • General Physics and Astronomy


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