Repeatable Photoactive Stent-Based Catheter to Enhance Therapeutic Efficacy for Esophageal Carcinoma

Localized photodynamic therapy (PDT) using a photoactive stent-based catheter involves the direct delivery of reactive oxygen species to the mucosa in esophageal carcinoma; however, the damaged mucosa recovers within 2 to 4 weeks, which considerably limits the clinical application of PDT. Here, we used aluminum(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) as a photosensitizer due to its excellent photochemical durability, low photobleaching, and high quantum yield and investigated whether repeated and periodic PDT via an AlPcS4-embedded stent-based catheter can provide sustained therapeutic efficacy. AlPcS4 was uniformly embedded in silicone membranes via coordination bonding to form a photoactive stent-based catheter. The membrane demonstrated excellent photostability and consistent singlet oxygen generation under near-infrared irradiation, as evidenced by a 67.2% decrease in 9,10-dimethylanthracene fluorescence intensity, even after 90 J cm^-2 irradiation, markedly superior to methylene blue (15.3%) and chlorin e6 (30.9%). Repeated PDT effectively enhanced cell death rates in KYSE-70 cells. In the xenograft model, MRI-based volumetric analysis showed that the tumor volume change in the thrice-PDT group (57.40% ± 9.26%) was significantly lower than those in the control (212.07% ± 38.44%, <i>P</i> < 0.001) and once-PDT groups (130.77% ± 11.25%, <i>P</i> = 0.018), accompanied by apoptotic and necrotic tumor destruction. Repeated PDT at 1-week intervals was technically successful in the porcine esophagus, leading to progressive mucosal injury, luminal narrowing, and apoptosis, while demonstrating sustained therapeutic efficacy. Thus, the minimally invasive repeatable photoactive stent-based catheter may be an effective and safe approach for treating esophageal carcinoma.