Oxygen-economizing liposomes for synergistic photodynamic and starvation therapy

Abstract

Photodynamic therapy (PDT) shows great potential in cancer therapy. However, the therapeutic efficacy of PDT is limited by the hypoxic microenvironment in tumor tissue. In this research, photosensitizer chlorin e6 (Ce6) and glycolysis inhibitor 3-bromopyruvate (3BP) co-loaded liposomes are designed for synergistic photodynamic and starvation therapy. The size and morphology of the drug loaded liposomes are fully investigated by cryogenic transmission electron microscopy and dynamic light scattering. 3BP can block energy supply of cancer cells by inhibiting glycolysis for starvation therapy, which is confirmed by measuring intracellular lactate and ATP levels. Meanwhile, the intracellular oxygen consumption can be reduced by 3BP, which is able to relieve tumor hypoxic microenvironment, leading to improved therapeutic efficacy of PDT. The antitumor ability of the combined photodynamic and starvation therapy is investigated by in vitro and in vivo experiments. Such oxygen-economizing liposome provides a promising strategy for synergistic photodynamic cancer therapy.