3.2.1. Size

Size plays an important role in interactions with the biological system and many biological NP-related mechanisms such as cellular uptake and particle processing efficiency in the endocytic path depending on it [53]. Additionally, the ion release rate, the smaller size, the faster release rate, and the interactions with cell membranes [54]. In general, there is a size-dependent NP toxicity and, therefore, their ability to enter in the human system. As the particle size decreases, the surface/volume ratio increases. Therefore, their contacting surface will increase, which makes penetration into the body easier and increases their toxic effect [54]. NP sizes less than 50 nm through intravenous injection connect to all tissues faster and exert stronger toxic effects [55].

The NP size indicates their "in vivo" distribution, or pharmaceutical behavior [56], and their most direct impact on physiological activity. NP sizes larger than 1 μm cannot easily enter the cell, but they interact with proteins absorbed in the cells. NP sizes greater than 6 nm cannot be excreted by the kindness and accumulate in specific organs [57]. For example, cadmium selenide quantum dots contact stays in the tissue, which causes hepatotoxicity [58].

Sonavane et al. carried out studies on the bio-distribution and bioaccumulation in the blood of gold nanoparticle (AuNP) of different sizes. They observed that smaller ones stayed longer in the bloodstream and accumulated to a greater extent in all organs [59].
