It is well known that delivery efficiency to cells is highly dependent on particle size and the administered dose. However, there is a marked discrepancy in many reports, mainly due to the inconsistency in assessment of various parameters. In this particular research, we designed experiments using layered double hydroxide nanoparticles (LDH NPs) to specifically elucidate the effect of particle size, dose and dye loading manner on cellular uptake. Using the number of LDH NPs taken up by HCT-116 cells as the indicator of delivery efficiency, we found that (1) the size of sheet-like LDH in the range of 40-100 nm did not significantly affect their cellular uptake; (2) cellular uptake of 40 and 100 nm LDH NPs was increased proportionally to the number concentration below a critical value, but remained relatively constant beyond the critical value; and (3) the effect of the dye loading manner is mainly dependent on the loading capacity or yield. In particular, the loading capacity is determined by the NP specific surface area. This research may be extended to a larger size range to examine the size effect, but suggests that it is necessary to set up a protocol to evaluate the effects of NP's physicochemical properties on the cellular delivery efficiency. (c) 2014 Elsevier Inc. All rights reserved.