Abstract
The methods currently available to deliver functional labels and drugs to the cell cytosol are inefficient and this constitutes a major obstacle to cell biology (delivery of sensors and imaging probes) and therapy (drug access to the cell internal machinery). As cell membranes are impermeable to most molecular cargos, viral peptides have been used to bolster their internalisation through endocytosis and help their release to the cytosol by bursting the endosomal vesicles. However, conflicting results have been reported on the extent of the cytosolic delivery achieved. To evaluate their potential, we used gold nanoparticles as model cargos and systematically assessed how the functionalisation of their surface by either or both of the viral peptides TAT and HA2 influenced their intracellular delivery. We evaluated the number of gold nanoparticles present in cells after internalisation using photothermal microscopy and their subcellular localisation by electron microscopy. While their uptake increased when the TAT and/or HA2 viral peptides were present on their surface, we did not observe a significant cytosolic delivery of the gold nanoparticles.
Highlights
To gain access to the interior of cells, molecules and particles need to cross the cell membrane
The impact of the cell penetrating peptide TAT and the endosome-disrupting peptide HA2 on the intracellular delivery of gold nanoparticles was quantified by photothermal microscopy (Fig. 1)
Gold nanoparticles (5nm diameter) were functionalised with a self-assembled monolayer composed of the capping peptides CALNN and CCALNN-poly(ethylene glycol) (PEG) and a small proportion of either one or both of the functional peptides CALNN-TAT and CCALNN-dHA2
Summary
To gain access to the interior of cells, molecules and particles need to cross the cell membrane. The ability to deliver probes or drugs with preserved functions to the cell cytosol would have a large impact in cell biology, drug delivery and therapy. Despite reports suggesting that some nanomaterials can cross the cell membrane, very little convincing experimental evidence of direct cytosolic entry exists in the literature [1,2]. Eukaryotic cells exposure to nanomaterials such as gold nanoparticles tends to result in their uptake through various endocytotic processes. This has been known for over 5O years: one of the earliest application of gold
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