Translation of photodynamic therapy and photodiagnostics into the clinic: Status and obstacles

Abstract

Clinical translation of new diagnostic or therapeutic approaches is one of the gate keepers in the evolution of patient management. Photonics-based diagnostic technologies are spearheading clinical translation. In 2021, the publication count for searches of “Photodynamic (-therapy OR -diagnosis) AND clinical translation” started to pick up significantly. Indeed since 2021, 229 works are listed in Clarivate's Web of Science, of which 129 are reviews exemplifying the interest in this topic. In all works, nanotechnology-related investigations are dominant, but other developments in photosensitizer design are also prominent. Over 60% of all listed publications are generated by researchers from the People's Republic of China, reflecting the keen interest in enabling photodynamic therapy as cost-competitive therapy for oncology and other clinical indications. In late 2021, we set out to obtain an update on the translational status of photodynamic diagnostics and therapeutics with a special call for Translational Biophotonics. While only seven manuscripts were accepted for this issue, some of the trends observed during the Web of Science search are also noticed here. The vast majority of the accepted manuscripts originate from the People's Republic of China. Retrospective analyses of previously treated patient cohorts are dominant [1–4], covering keloids, genital warts, port-wine stain (PWS) and condyloma acuminatum treatment, indicating the predominance of these superficial non-oncological indications over oncological therapies in clinical translation. These clinical studies investigated PDT either as an adjuvant to standard therapies (as in the case of surgery for keloid treatment [1]) or as stand-alone therapy vs standard therapies (as in the case of PWS [2], condyloma acuminatum (with prior hair removal) [3] and genital warts [4]). While none of these studies resulted in game-changing advantages of PDT vs standard therapy or of PDT as adjuvant therapy or in combination with adjuvant measures, some reduction in recurrence in keloids, genital warts and port-wine stains were noted. All publications reported an increase in patient satisfaction due to the treatment. Patient acceptance is an often-underappreciated parameter for the widespread adoption of a novel therapy. The port-wine stain study is reporting a 10-year follow-up with stable results. Similar observations were also noted by van Raath et al [5], who reported no improvement in PWS outcome over the past 3 decades. The manuscript by Yao et al [6] reports on an oncological clinical study on chlorin e6 derivative mediated PDT treatments on 18 patients with cervical and vaginal low-grade squamous intraepithelial lesions. Very high rates of complete response and HPV remission were observed at the 6-month follow-up, higher than achieved, for example, with ALA-induced PpIX as reported recently [7, 8]. Shi et al demonstrated that combining surgery and two ALA-induced PpIX-mediated PDT treatments was successful in a patient with keratoacanthoma-like squamous cell carcinoma [9]. Over 5000 articles are now listed since 2020 in the Web of Science for the search terms “nanotechnology and (cancer or oncology)” when restricted to clinical research. Hence, the review by Gaber and Fadel [10] of 14 studies with nanoparticle-based PDT is timely. As for the clinical studies reported above, ongoing clinical trials with nanoparticle-mediated PDT focus predominantly on non-oncological indications, from acne, warts and vitiligo to tinea capitis. One of the major advantages of nanoparticle formulations beyond enabling multimodal therapies (chemo and thermal) is overcoming the hydrophobicity of the majority of photosensitizers. The hydrophilic nature of the nanoconstructs enables photosensitizer accumulation in subcellular compartments. We thank the reviewers who helped the authors improve their results' presentation and the Journal's staff for the professional completion of this issue.