The application of photodynamic therapy in plastic and reconstructive surgery

Abstract

Photodynamic therapy (PDT) is a modern clinical treatment paradigm with the advantages of high selectivity, non-invasiveness, rare side-effect, no obvious drug resistance and easy combination with other therapies. These features have endowed PDT with high focus and application prospects. Studies of photodynamic therapy have been expanded in a lot of biomedical and clinical fields, especially Plastic and Reconstructive Surgery (PRS) the author major in. In this review, we emphasize the mechanism and advances in PDT related to the PRS applications including benign pigmented lesions, vascular malformations, inflammatory lesions, tumor and others. Besides, combined with clinical data analysis, the limitation of PDT and current issues that need to be addressed in the field of PRS have also been discussed. At last, a comprehensive discussion and outlooking represent future progress of PDT in PRS.

Keywords: clinical application; photodynamic therapy; photosensitizer; plastic and reconstructive surgery; tumor.

FIGURE 1

Fundamentals of Photodynamic therapy. (A) Visible and near infra-red light spectrum showing the wavelengths (nm) of maximum tissue penetration by light (above) and absorbance maxima of selected photosensitizers (below); Chemical structures of common photosensitizers including PpIX, HPPH, Lu-Tex from Dobson et al. (2018). (B) Jablonski level diagram and two approaches of photodynamic therapy. (C) Penetration depth of different wavelengths of laser in tissue, UV, ultraviolet light; VIS, visible light; NIR, near infrared light. (D) PDT-induced effects. (E) PpIX absorption in vivo for different kinds of light source from Ozog et al. (2016).

FIGURE 2

PDT treatment for vascular malformations in the field of PRS. (A) Overview of endovascular laser-tissue interactions in pulsed dye laser (PDL) treatment of refractory port wine stain (PWS) skin. Yellow light-emitting PDL is used to selectively photothermolyze ectatic venules (blue structures) in predominantly papillary dermis from Chen et al. (2012).

FIGURE 3

PDT treatment for tumor in the field of PRS. (A) PDT treatment procedure. Step I: Patient with tumor before PDT. Steps II-III: The photosensitizer is taken up by most tissues, but it is retained longer in the tumor. The malignant lesion is irradiated selectively at the maximal tumor-to-normal-tissue drug ratio. Step IV: The photosensitizer clears gradually from all tissues while the tumor starts to shrink as a result of PDT-mediated tumor cell destruction. Step V: Complete tumor ablation and clearance of photosensitizer from Kalka et al. (2000). (B) Porphyrin metabolism under physiologic conditions in tumor cells during ALA-based PDT from Kalka et al. (2000). (C) Schematic illustration of Ce6/Ftn@MnO₂ used for FLI and MRI bimodal imaging-guided hypoxic malignant tumor therapy from Zhu et al. (2022) (D) Some PDT-associated apoptosis pathways involving plasma membrane death receptors, mitochondria, lysosomes and ER, caspases and Bcl-2 family proteins. Most photosensitizers for PDT bind to mitochondria, lysosomes and/or other intracellular membranes, including the ER from Oleinick et al. (2002).