This document discusses a novel potential treatment for triple-negative breast cancer involving oxyphotodynamic therapy. Triple-negative breast cancer does not respond to hormonal or HER2-targeted therapies. Researchers found that oxyphotodynamic therapy, which combines photodynamic therapy with an oxygen supply, more effectively inhibited the growth of triple-negative breast cancer cells compared to photodynamic therapy alone. The researchers also determined that metformin enhances the effects of oxyphotodynamic therapy, suggesting their combination may be a potential new treatment method for triple-negative breast cancer. However, further research is still needed to understand the specific mechanisms involved.

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A Novel Treatment For Triple-negative
Breast Cancer
Triple-negative breast cancer is a cancer that tests negative for estrogen receptors,
progesterone receptors, and excess HER2 protein. These results mean the growth of the
cancer is not fueled by the hormones estrogen and progesterone, or by the HER2 protein.
So, triple-negative breast cancer does not respond to hormonal therapy medicines or
medicines that target HER2 protein receptors.
This type of breast cancer accounts for 10-20% of all types of breast cancer. It has special
biological behavior and clinicopathological characteristics, and the prognosis is worse
than other types. For doctors and researchers, there is intense interest in finding new
medications that can treat this kind of breast cancer.
Photodynamic therapy is a novel method for the treatment of breast cancer. By combining
a photosensitizer with a corresponding light source, reactive oxygen species (ROS) are
generated to selectively destroy the diseased tissues, so as to kill the cancer cells. But at
the same time it will also lead to the formation of hypoxia in tumor tissues and reduce the
therapeutic effect.
Recently, the team of Professor Jin Hongjun from the Molecular Imaging Center of Sun
Yat-sen University No.5 Hospital and the Tumor Center of Sun Yat-sen University No.5
Hospital explored a novel method to improve hypoxia in photodynamic therapy, and

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preliminarily found that oxyphotodynamic therapy combined with metformin has the
potential to treat triple-negative breast cancer. The research was published in the Annals
of Translational Medicine (ATM,IF:3.297).
Hypoxia occurs during photodynamic therapy, and there is no effective treatment method.
At present, a large amount of research is focused on the improvement of light sources and
the development of third-generation nanomaterials. This research aims to solve the
problem of photodynamic hypoxia from the perspective of photodynamic therapy
equipment, transport the pure oxygen produced by physical oxygen production
technology to a specially designed irradiator integrated with gas, light and electricity.
Oxygen and light irradiation work synchronously in the treatment area to maintain stable
oxygen-enriched state in the local area and avoid the toxic and side effects of
nanomaterials.
The advantages of oxyphotodynamic therapy versus photodynamic therapy in triple
negative breast cancer were first explored. Aminolevulinic acid (ALA) mediated
photodynamic (PDT) and oxyphotodynamic (OPDT) were used to treat triple-negative
breast cancer cells MDA-MB-231 cells, and the 50% inhibitory concentrations (IC50) were
calculated to be 10.62±1.22 mM 和 7.71±1.26 mM. Compared with ordinary photodynamic
therapy, oxyphotodynamic therapy has obvious advantages in inhibiting the growth of
cancer cells.

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▲The inhibitory effect of ALA (A), ALa-PDT (B) and ALa-OPDT (C) on MDA-MB-231 cells at different
concentrations, and the cell survival rate (D) of the above three groups at different concentrations of ALA
were compared with that of the control group (0 mM).*, P < 0.05;* *, P < 0.01;* * *, P < 0.001.
At the same time, Professor Jin Hongjun’s team also found that metformin and
5-aminolevulinic acid (ALA)-mediated oxyphotodynamic therapy have a synergistic effect
in the treatment of tumors. The combined use of the two at different concentrations can be
calculated by CompuSyn software. It is concluded that the combination index (CI) is <1.
Under the confocal microscope, it can be seen that the expression of protoporphyrin IX
(PpIX) in the oxyphotodynamic therapy group has increased, confirming the enhancement
of the therapeutic effect. With the progress of oxyphotodynamic therapy, the supply of
oxygen can increase the generation of oxygen free radicals or singlet oxygen. And
ultimately lead to the death of tumor cells.
▲Micromirror analysis showed that metformin had the most significant therapeutic effect when it was
treated with ALA and oxyphotodynamic. (A, D, G, J) Protoporphyrin IX (PpIX); (B, E, H, K) Mitochondrial

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green fluorescent protein (MTG); (C, F, I, L) Protoporphyrin IX (PpIX) + mitochondrial green fluorescent
protein (MTG). The transmitting wavelength of PpIX was 610±20 nm and MTG 530±30 nm.
Therefore, researchers believe that oxyphotodynamic therapy can alleviate the hypoxia
problem in photodynamic therapy through physical oxygen supply. Combined
with metformin is a potential new method for the treatment of triple-negative breast cancer,
but the specific mechanism needs further research. This study provides a preliminary
basis for further research on the role of metformin combined with oxyphotodynamic
therapy in the treatment of recurrent or metastatic triple-negative breast cancer.
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Reference: [1] Pei X, Wang X, Xian J, Mi J, Gao J, Li X, et al. Metformin and oxyphotodynamic therapy as
a novel treatment approach for triple-negative breast cancer. Annals of Translational Medicine.
2020;8:1138-.