Biogenic nanobubbles for effective oxygen delivery and enhanced photodynamic therapy of cancer

Lin Song, Guohao Wang, Xuandi Hou, Shashwati Kala, Zhihai Qiu, Kin Fung Wong, Fei Cao, Lei Sun
Acta Biomaterialia2020
Tumor hypoxia is believed to be a factor limiting successful outcomes of oxygen-consuming cancer ther- apy, thereby reducing patient survival. A key strategy to overcome tumor hypoxia is to increase the preva- lence 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 ther- apy. However, the application of these bubbles is constrained by their poor stability, requiring major workarounds to increase their half-lives. In this study, we explore the potential of biogenic gas vesi- cles (GVs) as a new kind of oxygen carrier to alleviate tumor hypoxia. GVs, which are naturally 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(O 2 ) were added/tail-injected. Signifi- cant enhancement of tumor cell apoptosis and necrosis was also observed during photodynamic therapy (PDT) in the presence of lipid-GVs(O 2 ) both in vitro and in vivo . Lipid-GVs(O 2 ) alone induced no obvious change in cell viability in vitro or any apparent pathological abnormalities after mice were tail-injected with them. 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.

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