Development of Nano Oxygen Carrier for Enhanced Cancer Therapy

Abstract

Tumor hypoxia is believed to be a factor limiting successful outcomes of oxygen-consuming cancer therapy, thereby reducing patient survival. A key strategy to overcome tumor hypoxia is to increase the prevalence of oxygen at the tumor site. Oxygen-containing microbubbles/nanobubbles have been developed to supply oxygen and enhance the effects of therapies such as radiotherapy and photodynamic therapy. However, the application of these bubbles is constrained by their poor stability, with various ways have to be done to stabilize bubbles and increase their half-life. In this study, we explore the potential of biogenic gas vesicles (GVs) as a new kind of oxygen carrier to alleviate tumor hypoxia. GVs, which are natural-formed, gas-filled, protein-shelled compartments were modified on the surface of their protein shells by a layer of liposome. A substantial improvement of oxygen concentration was observed in hypoxic solution, in hypoxic cells, as well as in subcutaneous tumors when lipid-GVs(O2) were added/tail-injected. Besides, a significant enhancement of tumor cell apoptosis and necrosis was observed during photodynamic therapy (PDT) with the existence of lipid-GVs(O2) both in vitro and in vivo. Meanwhile, no obvious change of cell viability, as well as no apparent pathological abnormalities, was observed after mice were tail-injected with lipid-GVs. In all, lipid-GVs exhibited promising performance for intravenous gas delivery, enhanced PDT efficacy and low toxicity, a quality that may be applied to alleviate hypoxia in cancers, as well as hypoxia-related clinical treatments.