Blood perfusion was always lower in
tumor tissues as compared with that in surrounding normal tissues which lead to inadequate nanomedicine delivery to
tumors. Inspired by the upregulation of both
endothelin-1 (ET1) and its ETA receptor in
tumor tissues and the crucial contribution of ET1-ETA receptor signaling to maintain myogenic tone of
tumor vessels, we supposed that inhibition of ET1-ETA receptor signaling might selectively improve
tumor perfusion and help deliver nanomedicine to
tumors. Using human U87 MG
glioblastomas with abundant vessels as the
tumor model, immunofluorescence staining demonstrated that ETA receptor was overexpressed by in
glioblastomas tissues compared with normal brain tissues. A single administration of ETA receptor antagonist
BQ123 at the dose of 0.5 mg/kg could effectively improve
tumor perfusion which was evidenced by in vivo photoacoustic imaging. Additionally, a single treatment of
BQ123 could significantly improve the accumulation of nanoparticles (NPs) around 115 nm in
tumors with a more homogeneous distribution pattern by in vivo imaging, ex vivo imaging as well as in vivo distribution experiments. Furthermore,
BQ123 successfully increased the therapeutic benefits of
paclitaxel-loaded NPs and significantly elongated the survival time of orthotropic
glioblastomas-bearing animal models. In summary, the present study provided a new strategy to selectively improve
tumor perfusion and therefore benefit nanomedicine delivery for
tumor therapy. As ET1-ETA receptor signaling was upregulated in a variety of
tumors, this strategy might open a new avenue for
tumor treatment.