Focal photodynamic intracellular acidification as a cancer therapeutic
Matthew J Gdovin1, Nuha Kadri1, Lourdes Rios1
1The University of Texas at San Antonio, Department of Biology, United States.
Abstract:
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.
Insights
A novel light-activated therapy uses nitrobenzaldehyde to rapidly decrease cancer cell pH, inducing apoptosis. This targeted approach shows promise for treating various cancers, including breast, prostate, and pancreatic, with reduced side effects.
Area of Science:
- Biochemistry
- Oncology
- Photodynamic Therapy
Background:
- Cancer cells manipulate pH for survival and metastasis, particularly in hypoxic environments.
- Current pH-targeting therapies lack specificity and vary in efficacy across cancer types.
Purpose of the Study:
- To introduce a novel light-activated therapy targeting intracellular pH (pHi) for cancer treatment.
- To evaluate the efficacy of nitrobenzaldehyde (NBA) in inducing cancer cell death via intracellular acidification.
Main Methods:
- Light-activation of nitrobenzaldehyde to induce rapid, focal intracellular acidification.
- In vitro testing on non-cancerous and various cancer cell lines (breast, prostate, pancreatic).
- In vivo studies using mice with triple-negative breast cancer tumors.
Main Results:
- Nitrobenzaldehyde effectively induced pH-induced apoptosis in diverse cancer cell lines.
- Intracellular acidification significantly reduced tumor growth rates and improved survival in mice.
- Demonstrated efficacy of NBA-upconverting nanoparticles against breast cancer cells in vitro.
Conclusions:
- Light-activated nitrobenzaldehyde offers a targeted strategy for cancer therapy by inducing intracellular acidosis.
- This approach shows potential for broad applicability across multiple cancer types and in vivo settings.
- Further research into the underlying mechanisms of pH-induced apoptosis is warranted.
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