Nanoparticle mediated photodynamic therapy as a method to ablate oral cavity squamous cell carcinoma in preclinical models.

Abstract

Photodynamic therapy (PDT) is a tissue ablation technique able to selectively target tumour cells by activating the cytotoxicity of photosensitiser dyes with light. PDT is nonsurgical and tissue sparing, two advantages for treatments in anatomically complex disease sites such as the oral cavity. We have previously developed PORPHYSOME (PS) nanoparticles assembled from chlorin photosensitiser-containing building blocks (~94,000 photosensitisers per particle) and capable of potent PDT. In this study, we demonstrate the selective uptake and curative tumour ablation of PS-enabled PDT in three preclinical models of oral cavity squamous cell carcinoma: biologically relevant subcutaneous Cal-33 (cell-line) and MOC22 (syngeneic) mouse models, and an anatomically relevant orthotopic VX-2 rabbit model. Tumours selectively uptake PS (10 mg/kg, IV) with 6~40-fold greater concentration versus muscle 24 hours post-injection. Single PS-PDT treatment (100 J/cm2, 100 mW/cm2) of Cal-33 tumours yielded significant apoptosis in 65.7% of tumour cells. Survival studies following PS-PDT treatments demonstrated 90% (36/40) overall response rate across all three tumour models. Complete tumour response was achieved in 65% of Cal-33 and 91% of MOC22 tumour mouse models 14 days after PS-PDT, and partial responses obtained in 25% and 9% of Cal-33 and MOC22 tumours, respectively. In buccal VX-2 rabbit tumours, combined surface and interstitial PS-PDT (200 J total) yielded complete responses in only 60% of rabbits 6 weeks after a single treatment, whereas three repeated weekly treatments with PS-PDT (200 J/week) achieved complete ablation in 100% of tumours. PS-PDT treatments were well tolerated by animals with no treatment-associated toxicities and excellent cosmetic outcomes.