Quantifying Nanoparticle Cellular Uptake: Which Method is Best?

Abstract

Keywords:As the range of engineered nanoparticles (NPs) designed as specific carriers increases, for example for cell targeting and drug delivery, the question on how many NPs are interacting or are taken up by cells is becoming increasingly important for any potential biomedical application. On one hand, the delivered dose of such NPs to the targeted cells is a key parameter in the assessment of their efficiency to perform the desired action (e.g., deliver the therapeutic substance or induce a specific effect), on the other hand, the assessment of intracellular NPs is crucial also from the safety aspect as NPs might come unintentionally in contact by untargeted cells. Particularly from the regulative perspective, it is important that reproducible and reliable analytical methods for the intracellular quantification of NPs are available at an early stage in the development in order to correlate the cell burden of NPs with their possible effects at a cellular level. Which method is the best?The authors approached this matter by questioning senior scientists in the field of nanoscience about their personal views on the prime method for quantifying intracellular NPs. Although -at first glance -this is a seemingly straightforward enquiry, their responses were rather ambiguous yet consistent: in a nutshell, they all concluded the method of choice for the quantification of NP uptake mainly depends on the research question, the available analytical devices as well as on the type of NPs of interest. As of that, it is not possible to recommend one specific technique that could be used for quantification of all the different NPs types which exist nowadays. As well known from the convincing evidence from the literature, physicochemical properties of NPs such as their size, shape, core material and surface functionalization have a strong impact on NP cellular interaction including uptake, intracellular fate and induction of cell response but also require very different analytical methods. Various cutting-edge techniques have emerged during the last years which can quantify the NPs based on their distinctive characteristics, for example -chemical composition, optical properties, magnetic properties or electron density. Comprehensive reviews and in-depth discussions are readily available [1][2][3][4] and are not reiterated herein. For the purpose of this commentary, we have selected some of the most widely used analytical techniques in the nanoscientific biomedical community based on a review of the existing nanotoxicology studies published within the scope of the last 5 years. Noteworthy, we do not differentiate here between intracellular and cell associated NPs which can of course also influence the choice of a method, however, it is an important point which has to be considered for the interpretation of the result. And it is important to add that, depending on the community and the research field, quanti-

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