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Opt. Express"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:p>Photodynamic therapy shows promise as a minimally invasive, tumor-selective treatment, but it requires the presence of oxygen, often scarce within tumors. Such therapy can be potentiated by delivering hemoglobin-based oxygen carriers into tumors, but the appropriate carrier concentration and interval between their delivery and photodynamic therapy must be selected for a given treatment setting. Here we exploited the ability of photoacoustic imaging to non-invasively measure intratumoral oxygenation in order to optimize the delivery of oxygen carriers derived from human hemoglobin. In tumor-bearing mice, the largest increase in intratumoral oxygen saturation relative to baseline occurred 6\u2005h after injection of carriers at 600\u2005mg\/kg, and photodynamic therapy under this condition significantly magnified the effects on tumor apoptosis and growth. The oxygen carriers induced no obvious off-target toxicity, and their oxygenating effects declined substantially by 24\u2005h after injection, indicating that the oxygenation response was transient under the sampled conditions. Our results illustrate the power of photoacoustic imaging for optimizing the intratumoral delivery of hemoglobin-based oxygen carriers and subsequent photodynamic therapy. 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