Despite the intensive development and unique properties of iron-oxide-based magnetic nanoparticles (MNPs), their use as drug delivery systems has not yet entered clinical practice. There also remains a lack of data on their toxicity profile and behavior in the bioenvironment. A number of in-vitro studies have been performed, but these were carried out with various MNPs using various methods of bioevaluation and various cell lines, so they are not universally applicable. It is of vital importance that selection of any experimental set-up and parameters for MNP bioevaluation, as well as the cell lines used, are focused on the final application of the MNPs. In this review, the most commonly used in-vitro methods for bioevaluation of MNPs are presented, including their key advantages and shortcomings. This critical comparison of these methods should facilitate selection of the appropriate in-vitro bioevaluation methods, and define the already established protocols that are available in the literature. Thus, we present here the first comprehensive review of in-vitro bioevaluation methods currently available for MNP evaluation. Furthermore, we provide important guidelines for selection of the best method, to enable reliable comparisons of the biological properties of different MNPs, and hence to promote their efficient translation from research to clinical practice.
Keywords: Cell morphology; Cell uptake; Cytotoxicity; Drug delivery; In-vitro bioevaluation; Superparamagnetic iron-oxide nanoparticles.
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