Assessment of bimodal laser photodynamic therapy at wavelenths of 410 nm and 653 nm for oral precancerous lesions: An in vitro and in vivo study

Background: Oral mucosal leukoplakia, a prevalent precancerous condition, poses significant challenges in clinical management. Photodynamic therapy (PDT) is a common therapeutic strategy, its efficacy in clinical practice is often constrained. There is a pressing demand for innovations that can enhance the effectiveness of PDT and minimize its side effects in addressing oral precancerous lesions.

Materials and methods: This study employed m-THPC as a Photosensitizer and developed a novel light source with dual wavelengths of 410 nm/653 nm tailored to excite the Photosensitizer. We conducted photodynamic experiments using oral precancerous cell lines, OSCC cell line and animal models. In vitro cellular responses were assessed using colony formation, and cell Apoptosis assays. An oral precancerous mouse model was established to appraise the therapeutic efficacy of the treatments. Histopathological evaluation of Apoptosis was performed using TUNEL and immunohistochemical staining.

Results: The development of a dual-wavelength laser device is reported. m-THPC demonstrated an affinity for precancerous cells, preferentially accumulating in precancerous tissue in vitro. Activation of m-THPC with a 410 nm laser showed a robust photochemical effect, effectively inhibiting the proliferation and promoting the Apoptosis of precancerous cells in vitro. The combined application of 410 nm/653 nm wavelengths yielded superior therapeutic efficacy, compared to the individual emissions at 410 nm and 653 nm, in a precancerous lesion mouse model and was associated with fewer adverse reactions. Despite spectral mismatch with m-THPC, high-dose 532 nm irradiation achieved therapeutic efficacy comparable to dual-wavelength PDT in vivo. However, this dose-dependent enhancement was accompanied by exacerbated photothermal effects, resulting in significant adverse reactions including localized hyperthermia and nonspecific tissue damage.

Conclusion: The dual-wavelength PDT, optimized for m-THPC, exhibits superior photodynamic characteristics and excellent biosafety. It aligns well with realistic clinical applic ation scenarios and presents as an innovative and promising therapeutic modality for the treatment of oral leukoplakia.

Cell apoptosis; Dual wavelength; Free radicals; Oral mucosal leukoplakia; Photodynamic therapy; Precancerous lesions.