Nanoparticle-mediated Photodynamic Therapy as a Method to Ablate Oral Cavity Squamous Cell Carcinoma in Preclinical Models

• DOI: 10.1158/2767-9764.crc-23-0269
• Publication Date: 2024-02-29T17:45:40Z
• Authors: Axel Sahovaler; Michael S. Valic; Jason L. Townson; Harley H.L. Chan; Mark Zheng; Sharon Tzelnick; Tiziana Mondello; Alon Pener-Tessler; Donovan Eu; Abdullah El-Sayes; Lili Ding; Juan Chen; Catriona M. Douglas; Robert Weersink; Nidal Muhanna; Gang Zheng; Jonathan C. Irish
• Keywords: Photosensitizing Agents; Squamous Cell Carcinoma of Head and Neck; Organothiophosphorus Compounds; Mice; 03 medical and health sciences; 0302 clinical medicine; Photochemotherapy; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Humans; Animals; Nanoparticles; Mouth Neoplasms; Rabbits; Research Article

Abstract Photodynamic therapy (PDT) is a tissue ablation technique able to selectively target tumor cells by activating the cytotoxicity of photosensitizer dyes with light. PDT nonsurgical and sparing, two advantages for treatments in anatomically complex disease sites such as oral cavity. We have previously developed PORPHYSOME (PS) nanoparticles assembled from chlorin photosensitizer–containing building blocks (∼94,000 photosensitizers per particle) capable potent PDT. In this study, we demonstrate selective uptake curative PS-enabled three preclinical models cavity squamous cell carcinoma (OCSCC): biologically relevant subcutaneous Cal-33 (cell line) MOC22 (syngeneic) mouse models, an orthotopic VX-2 rabbit model. Tumors PS (10 mg/kg, i.v.) 6-to 40-fold greater concentration versus muscle 24 hours post-injection. Single nanoparticle–mediated (PS-PDT) treatment (100 J/cm2, 100 mW/cm2) tumors yielded significant apoptosis 65.7% cells. Survival studies following PS-PDT demonstrated 90% (36/40) overall response rate across all models. Complete was achieved 65% 91% 14 days after PS-PDT, partial responses obtained 25% 9% tumors, respectively. buccal combined surface interstitial (200 J total) complete only 60% rabbits 6 weeks single whereas repeated weekly J/week) 100% tumors. were well tolerated animals no treatment-associated toxicities excellent cosmetic outcomes. Significance: safe repeatable modality OCSCC ablation. reproducible efficacy effectiveness multiple superior other clinically tested drugs. Cosmetic functional outcomes excellent, detected. These results are enabling window opportunity trials fluorescence-guided patients early-stage scheduled surgery.