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Photothermally Triggered Endosomal Escape and Its Influence on Transfection Efficiency of Gold-Functionalized JetPEI/pDNA Nanoparticles

Plasmonic nanoparticles for drug delivery have attracted increasing interest over the last few years. Their localized surface plasmon resonance causes photothermal effects on laser irradiation, which allows for delivering drugs in a spatio-temporally controlled manner. Here, we explore the use of go...

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Autores principales: Vermeulen, Lotte M. P., Fraire, Juan C., Raes, Laurens, De Meester, Ellen, De Keulenaer, Sarah, Van Nieuwerburgh, Filip, De Smedt, Stefaan, Remaut, Katrien, Braeckmans, Kevin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121899/
https://www.ncbi.nlm.nih.gov/pubmed/30110965
http://dx.doi.org/10.3390/ijms19082400
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author Vermeulen, Lotte M. P.
Fraire, Juan C.
Raes, Laurens
De Meester, Ellen
De Keulenaer, Sarah
Van Nieuwerburgh, Filip
De Smedt, Stefaan
Remaut, Katrien
Braeckmans, Kevin
author_facet Vermeulen, Lotte M. P.
Fraire, Juan C.
Raes, Laurens
De Meester, Ellen
De Keulenaer, Sarah
Van Nieuwerburgh, Filip
De Smedt, Stefaan
Remaut, Katrien
Braeckmans, Kevin
author_sort Vermeulen, Lotte M. P.
collection PubMed
description Plasmonic nanoparticles for drug delivery have attracted increasing interest over the last few years. Their localized surface plasmon resonance causes photothermal effects on laser irradiation, which allows for delivering drugs in a spatio-temporally controlled manner. Here, we explore the use of gold nanoparticles (AuNP) as carriers for pDNA in combination with pulsed laser irradiation to induce endosomal escape, which is currently considered to be one of the major bottlenecks in macromolecular drug delivery on the intracellular level. In particular, we evaluate nanocomplexes composed of JetPEI (polyethylenimine)pDNA and 10 nm AuNP, which do not exhibit endosomal escape by themselves. After incubating HeLa cells with these complexes, we evaluated endosomal escape and transfection efficiency using low- and high-energy laser pulses. At low laser energy heat is produced by the nanocomplexes, while, at higher laser energy, explosive vapour nanobubbles (VNB) are formed. We investigated the ability of heat transfer and VNB formation to induce endosomal escape and we examine the integrity of pDNA cargo after inducing both photothermal effects. We conclude that JetPEI/pDNA/AuNP complexes are unable to induce meaningful transfection efficiencies because laser treatment causes either dysfunctionality of the cargo when VNB are formed or forms too small pores in the endosomal membrane to allow pDNA to escape in case of heating. We conclude that laser-induced VNB is the most suitable to induce effective pDNA endosomal escape, but a different nanocomplex structure will be required to keep the pDNA intact.
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spelling pubmed-61218992018-09-07 Photothermally Triggered Endosomal Escape and Its Influence on Transfection Efficiency of Gold-Functionalized JetPEI/pDNA Nanoparticles Vermeulen, Lotte M. P. Fraire, Juan C. Raes, Laurens De Meester, Ellen De Keulenaer, Sarah Van Nieuwerburgh, Filip De Smedt, Stefaan Remaut, Katrien Braeckmans, Kevin Int J Mol Sci Article Plasmonic nanoparticles for drug delivery have attracted increasing interest over the last few years. Their localized surface plasmon resonance causes photothermal effects on laser irradiation, which allows for delivering drugs in a spatio-temporally controlled manner. Here, we explore the use of gold nanoparticles (AuNP) as carriers for pDNA in combination with pulsed laser irradiation to induce endosomal escape, which is currently considered to be one of the major bottlenecks in macromolecular drug delivery on the intracellular level. In particular, we evaluate nanocomplexes composed of JetPEI (polyethylenimine)pDNA and 10 nm AuNP, which do not exhibit endosomal escape by themselves. After incubating HeLa cells with these complexes, we evaluated endosomal escape and transfection efficiency using low- and high-energy laser pulses. At low laser energy heat is produced by the nanocomplexes, while, at higher laser energy, explosive vapour nanobubbles (VNB) are formed. We investigated the ability of heat transfer and VNB formation to induce endosomal escape and we examine the integrity of pDNA cargo after inducing both photothermal effects. We conclude that JetPEI/pDNA/AuNP complexes are unable to induce meaningful transfection efficiencies because laser treatment causes either dysfunctionality of the cargo when VNB are formed or forms too small pores in the endosomal membrane to allow pDNA to escape in case of heating. We conclude that laser-induced VNB is the most suitable to induce effective pDNA endosomal escape, but a different nanocomplex structure will be required to keep the pDNA intact. MDPI 2018-08-14 /pmc/articles/PMC6121899/ /pubmed/30110965 http://dx.doi.org/10.3390/ijms19082400 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vermeulen, Lotte M. P.
Fraire, Juan C.
Raes, Laurens
De Meester, Ellen
De Keulenaer, Sarah
Van Nieuwerburgh, Filip
De Smedt, Stefaan
Remaut, Katrien
Braeckmans, Kevin
Photothermally Triggered Endosomal Escape and Its Influence on Transfection Efficiency of Gold-Functionalized JetPEI/pDNA Nanoparticles
title Photothermally Triggered Endosomal Escape and Its Influence on Transfection Efficiency of Gold-Functionalized JetPEI/pDNA Nanoparticles
title_full Photothermally Triggered Endosomal Escape and Its Influence on Transfection Efficiency of Gold-Functionalized JetPEI/pDNA Nanoparticles
title_fullStr Photothermally Triggered Endosomal Escape and Its Influence on Transfection Efficiency of Gold-Functionalized JetPEI/pDNA Nanoparticles
title_full_unstemmed Photothermally Triggered Endosomal Escape and Its Influence on Transfection Efficiency of Gold-Functionalized JetPEI/pDNA Nanoparticles
title_short Photothermally Triggered Endosomal Escape and Its Influence on Transfection Efficiency of Gold-Functionalized JetPEI/pDNA Nanoparticles
title_sort photothermally triggered endosomal escape and its influence on transfection efficiency of gold-functionalized jetpei/pdna nanoparticles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121899/
https://www.ncbi.nlm.nih.gov/pubmed/30110965
http://dx.doi.org/10.3390/ijms19082400
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