Inhibiting redox-mediated endothelial migration by gadofullerenes for inducing tumor vascular normalization and improving chemotherapy.

Fullerene nanoparticles inhibit endothelial cell migration in vitro depending on their anti-oxidation. The alanine-modified gadofullerene (GFA) with the highest ROS quenching ability showed a notable TVN effect in vivo. The protein microarray revealed that GFA could restrain focal adhesion signaling pathway to prevent endothelial migrations. Benefiting from this, GFA could enhance the anti-tumor efficacy of chemotherapy via TVN. [Display omitted] Tumor vascular normalization (TVN) reverses abnormal tumor vasculatures, which could boost anti-cancer efficiency and especially increase drug intratumoral delivery. Endothelial cells play a vital role in angiogenesis, yet continuous modulating endothelial cell migration to improve TVN is ingenious but challenging. Here we propose a potential strategy for TVN based on inhibiting endothelial migration using antioxidative fullerene nanoparticles (FNPs). We demonstrate that FNPs inhibit cell migration upon their anti-oxidation effects in vitro. The optimized alanine-modified gadofullerene (GFA) exhibits superior TVN ability and inhibits tumor growth in vivo. Mechanically, facilitated with the protein microarray, we confirm that GFA could suppress the focal adhesion pathway to restrain endothelial migration. Subsequently, remarkable anti-tumor efficacy of chemotherapy synergy was obtained, which benefited from a more normalized vascular network by GFA. Together, our study introduces the potential of FNPs as promising TVN boosters to consider in cancer nanomedicine design. [ABSTRACT FROM AUTHOR]