Cellular uptake and intracellular fate of gold nanoparticles
Dpt. Chimie, Université Liverpool
Mon, Nov. 17th 2008, 14:00
Bât. C5 P.421A, CEA-Grenoble
Gaining the ability to invade living cells with nanoscopic objects that can act as probes to report intracellular molecular events, selectively repair or destroy cell compartments or deliver a molecular payload to an intracellular target site, is a fascinating prospect. If this endeavour can be developed into a robust technology, opportunities of innovative developments will arise including new research tools in molecular biology, methods of gene and drug delivery, diagnostics and therapeutics. The selective killing of cells in view of cancer therapy is only one of the potential health care applications that motivate research in this area.
Of all candidates for the role of cell-invading objects, gold nanoparticles appear to be most promising, primarily due to their stability, which enables them to survive the testing chemical environment inside biological cells. Other outstanding properties of relevance are the ease with which they can be modified with biomolecular functionalities, their optical properties that include strong light absorption, resonance light scattering and Raman enhancement, and their excellent visibility in electron microscopy.
This lecture summarises the most important preparative strategies for gold nanoparticles modified with those biomolecular functionalities that are needed to control cellular uptake and intracellular behaviour. A detailed transmission electron microscopic study reveals the effects of modifying the particles with cell penetrating peptides (CPPs) and signal peptides specific for different organelles. While particulate matter taken up by endocytosis usually remains confined to the endosome of the cell, it is demonstrated here that under certain conditions a significant number of particles can escape this fate and are freely available in the cytoplasm, from where they can reach further targets such as the nucleus or the mitochondria, depending on their surface modification with signal peptides. An alternative approach to endosomal escape is demonstrated by localised laser heating of the particles. It is shown that at laser powers that are not fatal for the cells endosomes filled with gold nanoparticles can be selectively destroyed and subsequently release the particles into the cytoplasm. HeLa cells, a well-known human fibroblast cell line, have been used in all experiments.
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