Аннтотация

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 overcome this problem by exploring additional surface modifications to UCNP@PEI to create biocompatible 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 (24h) and subacute (120h) 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 non-digesting mass spectrometry protocol. Our results, specified for the individual coatings, show that despite beneficial effect on biocompatibility, 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 biocompatibility and photophysical properties of post-modification UCNPs. We present an optimised 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.