Quantum dots are time bomb: Multiscale toxicological study

Nanotechnology and nanoscience have become a lifesaver for the problems of today's generation, and have been reported in many systems [[1], [2], [3], [4], [5]]. Quantum dots (QDs) are semiconductor nanocrystals, which are the most important group of nanomaterials. Because of their unique optical properties, research in the development of various biomedical applications has been one of the most popular in the last 10 years. Most of the efforts of scientists have been aimed at the configuration of properties of nanocrystals, reducing their size, and improving their optical characteristics [[6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23]]. There are various types of quantum dots: CdS, PbS, InP, graphene QDs, etc. [13,20,[24], [25], [26], [27], [28]]. As before, cadmium QDs outperform all others by quantum yield, half-height fluorescence peak width (FWHM), photostability and ability to set a fluorescence peak in a wide range (390–800 nm), as well as by the cost and ease of synthesis [14,23,24,29].

Recent reviews show that various cadmium-based QDs have IC50 values ranging from 19 to 696 μg/ml, ZnO-based QDs from 5.75 to 125 μg/ml, Ag2S-based from 23.2 to 1.361 μg/ml, AgInS2-based from 57.523 μg/ml, CuO-based from 7.4 μg/ml, graphene-based QDs from 24.81 to 2.000 μg/ml [30,31]. We obtained QDs. During the process toxicity was reduced due to obtaining more chemically stable nanocrystals and their encapsulation in a biocompatible shell of polyvinylpyrrolidone and maleic acid. We investigated the cytotoxicity of QDs and their conjugates with antibodies, their fragments, and BSA on various cell types. IC50 values ranging from 324 to 776 μg/ml were calculated. Meanwhile, in the due course of the experiment the IC50 for free QDs was not reached (IC50 > 1000 μg/ml). The results of all these studies show considerable variation in the cytotoxicity of QDs of different structures and compositions and can range from “Potentially very toxic” (IC50 < 10 μg/ml) to “Potentially non-toxic” (IC50 > 1000 μg/ml).

In in vivo studies, an extensive number of works focused on the toxicity of various QDs at single administration. These studies showed weak or no toxic effects of QDs on animals, mainly the effect was in the form of weight loss in animals [[33], [34], [35]]. At the same time, a number of publications shows that even with long-term observation of animals no toxic effects from a single administration of QDs were detected, including the administration of cadmium QDs [[36], [37], [38], [39], [40], [41], [42]]. Such data can cause a so called “illusory correlation” that QDs have a significant potential for the development of diagnostic and theranostic drugs. Drug safety is the key parameter. To determine the prospects for this area we carefully planned and conducted research to study the toxicity of cadmium QDs encapsulated in a copolymer shell. This allowed us to obtain a wide range of new data giving an insight into the main toxic effects and target organs during single and multiple IV administration of QDs into the body.

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