The Efficacy of Nanoparticle Delivery to Hypoxic Solid Tumors by ciRGD Co‐Administration Depends on Neuropilin‐1 and Neutrophil Levels

Abstract The ability to improve nanoparticle delivery to solid tumors is an actively studied domain, where various mechanisms are looked into. In previous work, the authors have looked into nanoparticle size, tumor vessel normalization, and disintegration, and here it is aimed to continue this work by performing an in‐depth mechanistic study on the use of ciRGD peptide co‐administration. Using a multiparametric approach, it is observed that ciRGD can improve nanoparticle delivery to the tumor itself, but also to tumor cells specifically better than vessel normalization strategies. The effect depends on the level of tumor perfusion, hypoxia, neutrophil levels, and vessel permeability. This work shows that upon characterizing tumors for these parameters, conditions can be selected that can optimally benefit from ciRGD co‐administration as a means to improve NP delivery to solid tumors.