The abnormal tumor vasculature in
solid tumors creates hypoxia
and leads to compromising the delivery and anticancer efficiency of
nanomedicine. Nanomaterials with intrinsic antiangiogenesis ability
might normalize tumor vessels and improve the therapeutic effect of
O2-related treatment like PDT. Herein, we designed and
prepared ROS-responsive side-chain selenium-grafted polymers, which
had potential antiangiogenic activity, as vehicles to load photodynamic
therapeutic agent Ce6 and chemotherapeutic drug oridonin. Under NIR
irradiation, the C–Se bonds on the side chain of polymers could
be cleaved in the presence of 1O2 produced by
Ce6 and further formed organic selenic acid through selenoxide elimination
reaction. The generated seleninic acid could downregulate the expression
of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2
(MMP-2) to inhibit angiogenesis and further relieve hypoxia. The released
oridonin could significantly increase the intracellular ROS concentration.
Both could modulate cancer cells’ microenvironment to reinforce
PDT. Therefore, these nanomedicines could be a good candidate for
synergistic treatments of antiangiogenesis treatment, PDT, and chemotherapy.