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Photothermally triggered endosomal escape and its influence on transfection efficiency of gold-functionalized JetPEI/pDNA nanoparticles

Lotte Vermeulen (UGent) , Juan Fraire (UGent) , Laurens Raes (UGent) , Ellen De Meester (UGent) , Sarah De Keulenaer (UGent) , Filip Van Nieuwerburgh (UGent) , Stefaan De Smedt (UGent) , Katrien Remaut (UGent) and Kevin Braeckmans (UGent)
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Abstract
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.
Keywords
gold nanoparticles, plasmonic effects, endosomal escape, pDNA delivery, INTRACELLULAR DELIVERY, OPTICAL-PROPERTIES, MEDIATED DELIVERY, RELEASE, CELLS, SIRNA, DRUG, DNA, MACROMOLECULES, FUNDAMENTALS

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Chicago
Vermeulen, Lotte, Juan Fraire, Laurens Raes, Ellen De Meester, Sarah De Keulenaer, Filip Van Nieuwerburgh, Stefaan De Smedt, Katrien Remaut, and Kevin Braeckmans. 2018. “Photothermally Triggered Endosomal Escape and Its Influence on Transfection Efficiency of Gold-functionalized JetPEI/pDNA Nanoparticles.” International Journal of Molecular Sciences 19 (8).
APA
Vermeulen, Lotte, Fraire, J., Raes, L., De Meester, E., De Keulenaer, S., Van Nieuwerburgh, F., De Smedt, S., et al. (2018). Photothermally triggered endosomal escape and its influence on transfection efficiency of gold-functionalized JetPEI/pDNA nanoparticles. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 19(8).
Vancouver
1.
Vermeulen L, Fraire J, Raes L, De Meester E, De Keulenaer S, Van Nieuwerburgh F, et al. Photothermally triggered endosomal escape and its influence on transfection efficiency of gold-functionalized JetPEI/pDNA nanoparticles. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2018;19(8).
MLA
Vermeulen, Lotte, Juan Fraire, Laurens Raes, et al. “Photothermally Triggered Endosomal Escape and Its Influence on Transfection Efficiency of Gold-functionalized JetPEI/pDNA Nanoparticles.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 19.8 (2018): n. pag. Print.
@article{8570822,
  abstract     = {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.},
  articleno    = {2400},
  author       = {Vermeulen, Lotte and Fraire, Juan and Raes, Laurens and De Meester, Ellen and De Keulenaer, Sarah and Van Nieuwerburgh, Filip and De Smedt, Stefaan and Remaut, Katrien and Braeckmans, Kevin},
  issn         = {1422-0067},
  journal      = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
  language     = {eng},
  number       = {8},
  pages        = {18},
  title        = {Photothermally triggered endosomal escape and its influence on transfection efficiency of gold-functionalized JetPEI/pDNA nanoparticles},
  url          = {http://dx.doi.org/10.3390/ijms19082400},
  volume       = {19},
  year         = {2018},
}

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