Complexity of the Nano-Bio Interface and the Tortuous Path of Metal Oxides in Biological Systems

Abstract

Metal oxide nanoparticles (NPs) have received a great deal of attention as potential theranostic agents. Despite extensive work on a wide variety of metal oxide NPs, few chemically active metal oxide NPs have received Food and Drug Administration (FDA) clearance. The clinical translation of metal oxide NP activity, which often looks so promising in preclinical studies, has not progressed as rapidly as one might expect. The lack of FDA approval for metal oxide NPs appears to be a consequence of the complex transformation of NP chemistry as any given NP passes through multiple extra- and intracellular environments and interacts with a variety of proteins and transport processes that may degrade or transform the chemical properties of the metal oxide NP. Moreover, the translational models frequently used to study these materials do not represent the final therapeutic environment well, and studies in reduced preparations have, all too frequently, predicted fundamentally different physico-chemical properties from the biological activity observed in intact organisms. Understanding the evolving pharmacology of metal oxide NPs as they interact with biological systems is critical to establish translational test systems that effectively predict future theranostic activity.

Size-Related Pathway Flux Analysis of Ultrasmall Iron Oxide Nanoparticles in Macrophage Cell RAW264.7 for Safety Evaluation

“…This ratio coincided with the relevant report that approximately one-third of internalized FITC-nanoceria colocalized with lysosomes . Moreover, S1 and S2 in the lysosome pathway were more than that of S3, in agreement with previous research showing that 4 to 22 nm sized gold nanoparticles were degraded in vitro by lysosomes in fibroblasts …”

“…38 Moreover, S1 and S2 in the lysosome pathway were more than that of S3, in agreement with previous research showing that 4 to 22 nm sized gold nanoparticles were degraded in vitro by lysosomes in fibroblasts. 38 Excessive USIONPs would cause cells to bear pressure for a short time, and they would first initiate the recycling endosome pathway to discharge them. Taking S2 as an example, the recycling endosome pathway probably shared about 23% of the total influx; ∼ 40% of USIONPs would flow to the Golgi apparatus with secreting 13% of USIONPs to outside of cells; 27% of USIONPs remained in the Golgi apparatus, and endoplasmic reticulum would be excreted and degraded through the autophagy pathway.…”

“…The least uptake of S1 was due to small nanoparticles having to overcome cytomembrane resistance when entering into cells, while S2 and S3 were easier to overcome cytomembrane resistance and permeate cytomembrane due to their larger size and mass. Thereby, the uptake amounts of S2 and S3 were more than that of S1, ,− in agreement with previous research showing that the optimum cellular uptake of nanoparticles is achieved with sizes ranging from 10 to 50 nm . García et al found that 14 nm of gold nanoparticles have higher internalization efficiency than 5 nm in MDA.MB.231 cells .…”

“…There was a size effect on the transport of nanoparticles, which was very important to optimize the size design of nanoparticles. For example, small-sized nanoparticles (similar to S1) could be designed to play functions after lysosomal degradation . Contrastingly, the route of endosome–Golgi–endoplasmic reticulum (ER) was exploited as a safe trafficking pathway for nanodrug transportation, such as cholera toxin and some virus-mediated drug delivery systems. , …”

Perturbation of Cellular Redox Homeostasis Dictates Divergent Effects of Polybutyl Cyanoacrylate (PBCA) Nanoparticles on Autophagy

“…Alterations in redox balance are frequently reported to be the underlying mechanism of NP-induced cellular effects [ 10 , 11 , 12 ]. However, with the exception of metal-based NPs that may directly generate ROS through Fenton and Fenton-like reactions [ 58 , 59 ], it is completely unknown how NPs alter cellular redox capacity. The nano–bio interface includes interactions between NPs and proteins, cellular membranes and biofluids, all of which may directly or indirectly influence cellular redox states [ 12 ].…”