Light Dosage Optimization by Data-driven and Dynamic Modeling: in Blue Light Therapies

The therapeutic properties of light have been known for thousands of years, but photodynamic therapy (PDT) was only developed in the last century. Currently, PDT is in clinical trials for the oncology-the treatment of head and neck, brain, lung, pancreas, abdominal cavity, breast, prostate, and skin cancer. Advantages of the light-based therapies include rapid action and avoidance of drug resistance. The underlying mechanism of PDT is that the photosensitizers (PS) transform from their ground state (singlet state) into a relatively long-lived electronically excited state (triplet state) by the absorbing the photo energy, which, in turn, produces highly toxic reactive oxygen species (ROS) in cells. One difficulty of PDT is the administration of PS. Since the PS does not naturally exist, PDT relies on the exogenous PS which is administered by intravenous injection or topical application to the skin. This makes three disadvantages: first, the PS needs to be approved before it can be applied to patients; second, the adverse reaction of importing the exogenous PS can not be eliminated even if it is approved; and third, for the tumor under deep tissue, it is hard to import the PS to incidence area. Similar to PDT, the antimicrobial blue light (ABL) only relies on the endogenous PS (flavin and porphyrin molecules) to inactivate the microbes, which is safer to use. However, as it is named, ABL can be only used for treating diseases whose pathogen is microbes, but the tumor. The most common application of ABL is treating various microbial superficial infections, e.g., skin or membranes. Traditionally, topical antimycotic/ antibiotic drugs and more convenient oral azole agents are the main treatments for microbial infections. However, most pathogens have shown increased resistance to these drugs. Especially, the most famous one, methicillin-resistant Staphylococcus aureus (MRSA), was called ”superbug” which has evolved resistance to most antibiotic drugs. Fortunately, ABLwas proved to be effective in the inactivation of most pathogenic microbes, including MRSA, Candida Albicans, Escherichia coli. Further studies show that the inactivation effect did not significantly decrease after repeated ABL irradiation, which demonstrates the avoidance of resistance to ABL...