Gold nanoparticles as inducers of cell specific death response
Patra, Hirak Kumar; Dasgupta, Anjan K.
India

Background: Gold nanoparticle (GNP) is reported to be an appropriate imaging probe to detect cancer. This probe is normally based on conjugation of GNP with specific antibodies.
Results: The present paper investigates whether GNP even in absence of any such functionalization induces any specific cellular response. We report GNP induced death response in human carcinoma lung cell line A549. In contrast, the two other cell lines BHK21 (Baby hamster kidney Cells) and HepG2 (human hepatocellular liver carcinoma cell line) remained indifferent to GNP treatment. The specificity of the induction of death response in A549 cells implies that target for GNP is not universal to all cell types. Flow cytometric studies indicated that the response was dose dependent and had a threshold effect. At higher GNP concentration there was an asymmetric accumulation of GNP in the periphery outside the cell nucleus. This was confirmed by confocal microscopy, a green scattering (possibly, surface enhanced Raman Effect) appearing on selective z-slices of the image.
Summary and Interpretation: The primary observation that deserves mention, is that gold nanosurface in spite of its chemical neutrality evokes a cell specific death response. While, absence of such responses in certain cells, e.g human leukaemia already reported is true, it may not be universal for all cells or cell types. The induction of cell death in the human lung carcinoma cells, A549 cell line has an all-none character as the cells exhibited this behaviour only after a certain period of GNP incubation (~24hrs.). A concentration threshold (30 nM) exists for GNP.At high concentration GNP accumulates at a region adjacent to the cell nucleus, the clustering being polarized in a small niche around the nucleus. This clustering was detectable in a fluorescent microscope and also by confocal imaging. The origin of this microscopically detectable inelastic scattering could be a surface enhanced Raman Effect. The point that we would like to highlight is that GNP is more than a mere vehicle, there may be a direct cross talk between GNP and cellular and (or) subcellular receptors in certain cells. The understanding of the origin of such cell specific response may be an important step forward in nanomedicine involving gold.
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