Rational surface design of upconversion nanoparticles with polyethylenimine (PEI) coating for biomedical applications: better safe than brighter?

Anna E. Guller, Annemarie Nadort, Alla N. Generalova, Evgeny V. Khaydukov, Andrey V. Nechaev, Inna A. Kornienko, Elena V. Petersen, Liuen Liang, Anatoly B. Shekhter, Yi Qian, Ewa M. Goldys, Andrei V. Zvyagin

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


Upconversion nanoparticles (UCNPs) coated with polyethylenimine (PEI) are popular background-free optical contrast probes and efficient drug and gene delivery agents attracting attention in science, industry, and medicine. Their unique optical properties are especially useful for subsurface nanotheranostics applications, in particular, in skin. However, high cytotoxicity of PEI limits safe use of UCNP@PEI, and this represents a major barrier for clinical translation of UCNP@PEI-based technologies. Our study aims to address this problem by exploring additional surface modifications to UCNP@PEI to create less toxic and functional nanotheranostic materials. We designed and synthesized six types of layered polymer coatings that envelop the original UCNP@PEI surface, five of which reduced the cytotoxicity to human skin keratinocytes under acute (24 h) and subacute (120 h) exposure. In parallel, we examined the photoluminescence spectra and lifetime of the surface-modified UCNP@PEI. To quantify their brightness, we developed original methodology to precisely measure the colloidal concentration to normalize the photoluminescence signal using a nondigesting mass spectrometry protocol. Our results, specified for the individual coatings, show that, despite decreasing the cytotoxicity, the external polymer coatings of UCNP@PEI quench the upconversion photoluminescence in biologically relevant aqueous environments. This trade-off between cytotoxicity and brightness for surface-coated UCNPs emphasizes the need for the combined assessment of the viability of normal cells exposed to the nanoparticles and the photophysical properties of postmodification UCNPs. We present an optimized methodology for rational surface design of UCNP@PEI in biologically relevant conditions, which is essential to facilitate the translation of such nanoparticles to the clinical applications.

Original languageEnglish
Pages (from-to)3143-3153
Number of pages11
JournalACS Biomaterials Science and Engineering
Issue number9
Publication statusPublished - 10 Sept 2018


  • upconversion nanoparticles
  • photoluminescence
  • surface modification
  • cytotoxicity
  • skin


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