Focal photodynamic intracellular acidification as a cancer therapeutic

Cancer cells utilize an array of proton transporters to regulate intra- and extracellular pH to thrive in hypoxic conditions, and to increase tumor growth and metastasis. Efforts to target many of the transporters involved in cancer cell pH regulation have yielded promising results, however, many productive attempts to disrupt pH regulation appear to be non-specific to cancer cells, and more effective in some cancer cells than others. Following a review of the status of photodynamic cancer therapy, a novel light-activated process is presented which creates very focal, rapid, and significant decreases in only intracellular pH (pHi), leading to cell death. The light-activation of the H⁺ carrier, nitrobenzaldehyde, has been effective at initiating pH-induced apoptosis in non-cancerous and numerous cancerous cell lines in vitro, to include breast, prostate, and pancreatic cancers. Also, this intracellular acidification technique caused significant reductions in tumor growth rate and enhanced survival in mice bearing triple negative breast cancer tumors. The efficacy of an NBA-upconverting nanoparticle to kill breast cancer cells in vitro is described, as well as a discussion of the potential intracellular mechanisms underlying the pH-induced apoptosis.