“…Immortalised hepatic cell lines, normally derived from human hepatocellular carcinoma, have been the "go-to" for researchers for decades for a variety of reasons, including their wide availability from certified cell line sources such as ATCC (i.e., the American Type Culture Collection, which is a non-profit organisation that collects, stores, and distributes standard reference cell lines and other research and development materials), or BIOPREDICT (whose most popular product is the Hep-aRG cell line), relative ease of handling and culture, lack of inter-donor variation [48,[58][59][60], long-term maintenance in culture with a stable phenotype (depending on cell type), and resistance to senescence [61]. For decades, in vitro 2D hepatocyte models have been successfully used to obtain pre-clinical data on many NBMs, including the liposomal forms of irinotecan (including studies undertaken in SK-Hep-1 cells) [62] and doxorubicin (HepG2 cells, among others), gold [63][64][65], SPIONs [66], and carrier NBMs such as poly(alkyl cyanoacrylate) or PACA [67,68] and poly(butyl cyanoacrylate) or PBCA.…”