Low-Cytotoxic Gold-Coated Silver Nanoflowers for Intracellular pH Sensing

Qiang Zhang, Han Wen, Kiri Watanabe, Ibuki Kotani, Monica Ricci, Beatrice Fortuni, Anh Thi Ngoc Dao, Akito Masuhara, Kenji Hirai, Hitoshi Kasai, Tomoko Inose, Hiroshi Uji-I

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Intracellular pH affects many biological processes such as apoptosis, proliferation, endocytosis, and multidrug resistance. In view of this, highly sensitive pH sensing in live cells is essential for understanding biological dynamics. Although surface enhanced Raman scattering (SERS) using noble metal nanoparticles functionalized with acidic ligands has been proposed for highly sensitive intracellular pH sensing, the dependence of SERS pH sensitivity on nanoparticle morphology has been overlooked. The apparent dissociation constant (pKa) of acid ligands is known to be sensitive to nanoparticle curvature. Thus, nanoparticle morphology should reflect SERS pH sensitivity. Here, we compared pKa behaviors and SERS pH sensitivities of nearly spherical isotropic and flowerlike anisotropic gold-coated silver nanoparticles (AuAgNPs and AuAgNFs, respectively). We found that the NPs with higher curvature such as AuAgNFs show a narrower pH-sensitive range (pH 5-8) compared to the nearly spherical nanoparticles, providing higher sensitivity to the pH range. Taking advantage of the narrow pH range of AuAgNFs, pH changes are successfully monitored as a function of time in cells treated with and without anticancer drugs, respectively. The results indicate that the pH-sensitive range of SERS-sensing can be tailored by controlling nanoparticle morphology. This tunability is a crucial requirement for pH-sensing applications in various biological systems.

Original languageEnglish
Pages (from-to)7643-7650
Number of pages8
JournalACS Applied Nano Materials
Issue number8
Publication statusPublished - 2020 Aug 28


  • cytotoxicity
  • intracellular pH sensing
  • nanoflower
  • on-demand
  • surface-enhanced Raman scattering


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