Biological Homeostasis-Inspired Light-Excited Multistage Nanocarriers Induce Dual Apoptosis in Tumors.

In the microenvironment of an organism, each element always regulates and compensates for each other's defects, finally achieving biostable equilibrium. Herein, inspired by the balance of biological homeostasis and the interconstraint of elements, light-responsive nanoparticle with anti-vascularization and oxygen-supplying ability such like a homeostasis body is constructed by the electrostatic adsorption of reactive oxygen species (ROS)-responsive copolymers with photosensitizers and oxygen donors, which act as the elements of homeostasis body can interact through multistage reactions forming a balance that induces double apoptosis including those caused by the photosensitizer itself and those induced after oxygenation. In this homeostasis body, the element photosensitizer can simultaneously generate hyperthermia and ROS. The former can not only inhibit the growth of blood vessels and promote cell necrosis, but induce the thermally responsive release of oxygen to alleviate tumor hypoxia for enhanced PDT. And the latter will induce rapid depolymerization of nanoparticles, promote the penetration and finally induce double apoptosis through multistage reactions. Immunofluorescence data further demonstrate that the nanoparticles significantly alleviated tumor hypoxia upon photoexcitation. Thus, such nanoparticles with multistage synergistic effects have demonstrated excellent effects in achieving biostable equilibrium to induce dual apoptosis and may also be a good strategy in hypoxic tumors therapy.