*2.2. Tumor Accumulation*

NPs accumulate preferentially in tumor tissues in comparison with the normal ones [22]. This is mainly because the vessels around the tumoral tissue have a higher permeability (than the normal vessels) and tumors have impaired lymphatic drainage, which leads to retention of the permeated NPs. This is an effect called enhanced permeation and retention (EPR) [23–25].

Tumors are densely packed with cells and the extracellular matrix. Thus, NP size plays an important role in the diffusion and accumulation inside the tumor. The accumulation within the tumors could be modulated by the NP physical dimensions and surface chemistry. In general, diffusion and NP size are inversely correlated [26]. Small size NPs can diffuse freely across tumoral tissue and present a widespread distribution within normal tissues. However, small NPs can easily and quickly clear out. Size is important for other purposes such as when NPs are applied as imaging agents helping to distinguish normal and pathological tissues because they appear only on the tumor periphery thanks to their bigger size.

As previously discussed, the biomolecules adsorption onto the NP surface is directly related with their opsonization and clearance capacity. Therefore, it is related with the blood concentration along with time.
