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 journalArticleResearchpeer-review

Abstract

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 the viability of normal cells exposed to the nanoparticles 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.

LanguageEnglish
Pages3143-3153
Number of pages11
JournalACS Biomaterials Science and Engineering
Volume4
Issue number9
DOIs
Publication statusPublished - 10 Sep 2018

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Polyethyleneimine
Nanoparticles
Coatings
Cytotoxicity
Photoluminescence
Luminance
Skin
Polymers
Functional materials
Biocompatibility
Medicine
Mass spectrometry
Surface treatment

Cite this

@article{03f2a7967d9242c699ccf3b7acd7d531,
title = "Rational surface design of upconversion nanoparticles with polyethylenimine (PEI) coating for biomedical applications: better safe than brighter?",
abstract = "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 the viability of normal cells exposed to the nanoparticles 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.",
keywords = "upconversion nanoparticles, photoluminescence, surface modification, cytotoxicity, skin",
author = "Guller, {Anna E.} and Annemarie Nadort and Generalova, {Alla N.} and Khaydukov, {Evgeny V.} and Nechaev, {Andrey V.} and Kornienko, {Inna A.} and Petersen, {Elena V.} and Liuen Liang and Shekhter, {Anatoly B.} and Yi Qian and Goldys, {Ewa M.} and Zvyagin, {Andrei V.}",
year = "2018",
month = "9",
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doi = "10.1021/acsbiomaterials.8b00633",
language = "English",
volume = "4",
pages = "3143--3153",
journal = "ACS Biomaterials Science and Engineering",
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publisher = "American Chemical Society",
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}

Rational surface design of upconversion nanoparticles with polyethylenimine (PEI) coating for biomedical applications : better safe than brighter? / Guller, Anna E.; Nadort, Annemarie; Generalova, Alla N.; Khaydukov, Evgeny V.; Nechaev, Andrey V.; Kornienko, Inna A.; Petersen, Elena V.; Liang, Liuen; Shekhter, Anatoly B.; Qian, Yi; Goldys, Ewa M.; Zvyagin, Andrei V.

In: ACS Biomaterials Science and Engineering, Vol. 4, No. 9, 10.09.2018, p. 3143-3153.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Rational surface design of upconversion nanoparticles with polyethylenimine (PEI) coating for biomedical applications

T2 - ACS Biomaterials Science and Engineering

AU - Guller,Anna E.

AU - Nadort,Annemarie

AU - Generalova,Alla N.

AU - Khaydukov,Evgeny V.

AU - Nechaev,Andrey V.

AU - Kornienko,Inna A.

AU - Petersen,Elena V.

AU - Liang,Liuen

AU - Shekhter,Anatoly B.

AU - Qian,Yi

AU - Goldys,Ewa M.

AU - Zvyagin,Andrei V.

PY - 2018/9/10

Y1 - 2018/9/10

N2 - 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 the viability of normal cells exposed to the nanoparticles 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.

AB - 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 the viability of normal cells exposed to the nanoparticles 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.

KW - upconversion nanoparticles

KW - photoluminescence

KW - surface modification

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