Project 9 (ICN)
Project 9: The life of NP in contact with biological media and entities
Fellow: Ngoc Tran (ESR9), 36 months
Tutors: Prof. Dr. Víctor Puntes (ICN)
We will explore the interaction of inorganic and biological matter at the nanoscale focusing on what happens to NP when they interact with cells. A set of characterization techniques will be protocolled to determine the physico-chemical state of the NP during their life. Thus, TEM, SQUID, DLS, Z-Potential, UV-VIS, XRD, SAXS will be used to study the NP itself while ICPMS, EDX, EELS, HAADF, FTIR-ATR and other methods will be used to study the NP atomic composition regarding the following aspects:
- Extended and strict formulation of the sample: Additives and unreacted precursors are normally present in NP preparations and they may have stronger biological effects than the NP themselves. Additionally, the different components of the colloid will have different histories. Similarly, tests for bacterial endotoxin and other biological contaminants often found in NP preparations will be performed.
- Aggregation: Dispersion of NP in biological media for toxicity testing may destabilize NP and lead to micrometric aggregates. The physico-chemical behaviour and biological impact of nanosized and microsized particles is different. We have observed that non-toxic colloids became toxic when the same particles were aggregated without any chemical modification in the formulation of the sample.
- Dissolution: cysteines have been observed to etch gold NP, chlorine ions dissolve silver NP and enzymes process CNTs. Inorganic NP can be dissolved in biological media in time frames ranging between days to weeks. This may be a particular source of toxic cations. In addition, the redox process of corrosion may also interfere with metabolism if produced inside or in the vicinity of the cell, in particular by inducing cellular stress.
- Mutation: The NP core may suffer (further) oxidation, crystal symmetry transition or reversible phase segregation which modifies the signatures and properties of the NP. A simple example is magnetite that can be spontaneously transformed into hematite in a short time scale due its nanometric size. In this example, the magnetic signal disappears but the iron oxide NP is still there.
- Protein corona: The NP surface may also suffer a number of modifications where the protein corona is one of the most significant. It may, in turn, strongly influence the bio-compatibility and bio-distribution of these particles. – A critical point is to evaluate the potential optical interference with the dyes used in biological assays since inorganic NP can be strongly active in the visible range, where, for example, plasmonic NP (like silver) can have absorption cross sections 10.000 times larger than organic dyes.
- Signatures of engineered inorganic NP will be addressed to detect and discern NP from the biological media (cell, tissue, organism, or environment) where they are dispersed.
Main skills acquired are both physical and biological assay systems, focusing on the structure- activity relationship and the mutability of the NP in biologically significant environments. Secondments to partners 1 (protein corona evolution), 2 (endotoxin testing), 6 (genotoxicity of modified NP), 12 (real life conditions for NP evolution).
In WP1 (task 1.5), WP3 (tasks 3.1, 3.2 and 3.3) and WP4 (task 4.1).