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19 Given the promises, concerns and commercial aspects of NPs, developing reliable and fast experimental protocols dedicated to the characterization of suspended NPs in biological media is pressing. 14–16 Although NP behavior in biological fluids is fundamental for either exploiting their potentially beneficial properties or mitigating the risks they may pose to human health and the environment, 17,18 our general understanding is still lagging behind current NP development. 12,13 In this context, the interaction of NPs with living matter has been heavily addressed over the past years. 11 All these various factors underline the complexity of these systems and importance of precisely understanding NP behavior in biologically relevant surroundings at a basic level, which is indispensable in developing any kind of nanomaterial for subsequent medical application.Ĭurrently, it is widely accepted that the cellular fate, as well as the subsequent absorption, distribution, metabolism, and clearance is dictated by the NP behavior in the biological environment. 10 NP aggregation, which is a common phenomenon in this complex environment, might also be induced and consequently has to be taken into account. 9 This has several critical consequences for example, a tightly bound immobile protein layer is known to form on the particle surface ( i.e., the so-called hard corona) and possibly a weakly associated mobile layer ( i.e., the soft corona). However, before NPs can actually interact with living cells/organisms, their surfaces are inevitably confronted to biological fluids – such as cell culture medium, blood or lung fluid – whose components ( i.e., bio- and small molecules, such as proteins, antibodies, salts/ions, vitamins, lipids) 8 will inevitably interact with the particle surfaces. 2 Significant progress has been made in the materials field in recent years, and NPs have been designed in virtually all shapes and sizes 3–7 to take advantage of their physico-chemical properties to a maximum degree. 1 This vast field includes designing NPs capable of targeting certain cells to deliver drugs, genetic material, NPs or nanofibers used for tissue engineering or nanoscale devices or sensors. Introduction The appeal of nanomedicine lies in its potential of addressing some of the most important and current challenges in diagnosis and treatment by exploiting the unique properties of nanoparticles (NPs). This approach yields information with an unprecedented signal-to-noise ratio in favour of the NPs and NP-biomolecule corona complexes, which in turn opens the frontier to scattering-based studies addressing the behaviour of NPs in complex physiological/biological fluids. We meet this challenge by building on depolarized scattering: Unwanted signals from the matrix are completely suppressed. However, when it comes to NPs in multicomponent and optically complex aqueous matrices – such as biological media and physiological fluids – light scattering suffers from lack of selectivity, as distinguishing the relevant optical signals from the irrelevant ones is very challenging. Light scattering is one of the few techniques available to adequately characterize suspended nanoparticles (NPs) in real time and in situ.
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