The effective treatment of metastatic cancer continues to be a challenge due to the highly invasive nature of
metastatic lesions and their propensity to develop therapeutic resistance. Optimal therapeutic regimens for
peritoneal metastases should have both rapid uptake and penetrate throughout cancerous lesions. Using in vitro
models of ovarian cancer, we have found that the cores of tumor nodules are both hypoxic and acidic, rendering
most chemotherapeutic agents ineffective, and considerably reducing the therapeutic efficacy of the majority of
photodynamic therapy (PDT) and radiation therapy regimens. PDT using EtNBS, a cationic photosensitizer, is a
promising approach for treating these hypoxic and acidic nodule cores as it rapidly accumulates into the hypoxic
cores of tumor nodules, and is effective even in completely anoxic environments. To improve the uptake rate of
EtNBS into cells, we utilized a carboxylic acid terminated derivative of EtNBS that is zwitterionic at biological
pH levels. In this study, we investigated the effect of this structural change on PDT efficacy in ovarian cancer
cells.
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