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.
Highlights
Gold nanoparticles (AuNPs) have attracted increasing interest as a promising new vehicle for gene therapy, stimulated by their basic physical, chemical and optical properties [1]
We investigated the ability of heat transfer and vapour nanobubbles (VNB) formation to induce endosomal escape and we examine the integrity of pDNA cargo after inducing both photothermal effects
We examined if photothermal effects such as heating and VNB formation were able to induce endosomal release and transfect HeLa cells
Summary
Gold nanoparticles (AuNPs) have attracted increasing interest as a promising new vehicle for gene therapy, stimulated by their basic physical, chemical and optical properties [1]. Synthesis and surface modifications are fairly straightforward and allow the preparation of a variety of AuNPs that are able to bind macromolecular therapeutics (e.g., proteins, siRNA, pDNA, etc.) [3]. Sacit.i2o0n18o, 1n9,e2n4d00osomal escape efficiency, pDNA integrity and final transfection efficiency. Wof 1e8 demonstrate that laser-induced VNB are clearly more efficient in disrupting the endosomal mtoeminvberastnigeattheatnhemuesreeohf eAautiNngP.sHfoorwspeavteiro,-tienmtphoercaul rcroennttroJleltePdEdI/epliDveNryAo/Af tuhNe PcaNrPgon. Wof 1e8 demonstrate that laser-induced VNB are clearly more efficient in disrupting the endosomal mtoeminvberastnigeattheatnhemuesreeohf eAautiNngP.sHfoorwspeavteiro,-tienmtphoercaul rcroennttroJleltePdEdI/epliDveNryAo/Af tuhNe PcaNrPgon. aAnuoNcoPms panledx,otthheer pmDeNtaAl NdoPess(ne.ogt.,suArgvi[v4e,5t]h, eChuig[6h]lyanindteAnlse[7p])hyarseickalnfoowrcnestowhhaevneVaNnBenarheafnocremdeodp. tOicnalthaebsoothrpetriohnanvdi,a wLhoiclaelitzheedgSeunrefraacteioPnlaosfmhoeantRiselseosnsadnacme (aLgSinPgR)t.oLpSDPNRAis, aencodnosseoqmuaelnecsecaopf ethies minutecrhaclteisosnebffeictwieenet.nWthee cforenecleuldecetrthonatsaofdtihffeerceonntdduecstiigonnobfaAnduNofPacmonettaailnNinPg annadnoacnoemxptelrenxaelsoisscnileleadtiendgtehlaetctirsosmtilalgcnaeptaicblfieeoldf , faosrmshionwg nVNinBFbiguutrteh1aAt p[o8s–e1s0l]e. ss stress on the pDNA
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