Inhibiting redox-mediated endothelial migration by gadofullerenes for inducing tumor vascular normalization and improving chemotherapy
Abstract
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 &lt;em&gt;in vitro&lt;/em&gt;. The optimized alanine-modified gadofullerene (GFA) exhibits superior TVN ability and inhibits tumor growth &lt;em&gt;in vivo&lt;/em&gt;. 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.</p><p> <a href="https://www.sciencedirect.com//science/article/pii/S2095927323004140/pdfft?pid=1-s2.0-S2095927323004140-main.pdf">View PDF</a>
