Fig. 5

Uniform parameters that determine NP delivery efficacy across different NP sizes do not exist. a UMAP plots for each and every tumor-associated parameter determined (as displayed in Fig. 4) as a function of UMAP coordinates. For analysis, all data points for each and every animal were combined for all groups (all differently sized NPs were analysed together). For every parameter, the values were first rescaled to a linear 0–1 scale with 0 being the lowest value for that parameter across all animals and 1 being the highest value for that parameter across all animals. Every single dot shown reveals a separate animal and indicates the specific value of the animal on its Y-axis, while for every animal, its position on the X-axis does not change and thus, values for all parameters can be directly compared. The dots were colour-coded based on the upper left plot (the total tumor NP uptake level), where the 25% of animals with highest NP tumor levels were coloured red, the 25% of animals with lowest NP tumor levels were coloured blue and the remaining animals with medium NP levels were coloured green. To determine whether a particular parameter promotes or inhibits NP delivery efficacy, the red and blue groups should be separated on the Y-axis for the parameter. The parameters with most distinction (but not complete) were TEC level and tumor perfusion. b Representative images for Au₄₀ NP treated mice having high (left column) or low (right column) NP delivery efficacy in the tumor. The top row show laminin-stained tumor blood vessels, indicating less laminin coverage in the low NP delivery group (scale bars: 50 µm). The second row shows NG2-stained tumor blood vessels, also indicating less pericyte (NG2) coverage in the low NP delivery group (scale bars: 50 µm). The third row shows H&E images, showing higher necrosis levels in the low NP delivery group. The fourth row shows PSR images, showing higher ECM density in the low NP delivery group