Hypoxia is a fundamental hallmark of solid
tumors and helps contribute to
chemotherapy resistance. Hyperbaric
oxygen (HBO)
therapy can overcome tumor hypoxia and promote
chemotherapy antitumor efficacy; however, the simultaneous administration of some conventional
chemotherapies, including
doxorubicin (DOX), with HBO is considered an absolute
contraindication. Here, DOX-loaded
liposome (
Doxil) is coadministered with HBO to assess the safety and efficacy of this combination treatment. By overcoming tumor hypoxia, HBO not only improves
Doxil tumor penetration by decreasing the
collagen deposition but also sensitizes
tumor cells to
Doxil. As a result, the combination treatment synergistically inhibits H22
tumor growth, with a
tumor inhibition rate of 91.5%. The combination of HBO with
Doxil shows neither extra side effects nor promotion of
tumor metastasis. These results collectively reveal that the combination of HBO with
Doxil is an effective and safe treatment modality. As both HBO and
Doxil are routinely used, their combination could quickly translate to clinical trials for patients with hypoxic solid
tumors.