Oxygenated collagenase nanoliposomes for deep photodynamic therapy via remodelling the tumor extracellular matrix

Melanoma is highly aggressive and remains difficult to treat. Traditional treatment options often result in damage to normal tissues and a high rate of recurrence. Conventional photodynamic therapy (PDT) is limited by poor light penetration, oxygen depletion, and extracellular matrix (ECM) barriers. In this study, we developed an acid-responsive liposome system that co-loads indocyanine green (ICG, a photosensitizer) and 1-bromoperfluorooctane (PFOB) modified with collagenase (Col-LIP-(ICG + PFOB)) to facilitate the degradation of the tumor extracellular matrix and enable near-infrared (NIR)-triggered PDT. Our findings demonstrated that Col-LIP-(ICG + PFOB) effectively degrades the tumor extracellular matrix via collagenase, resulting in increased accumulation of the formulation within the tumor. Upon NIR irradiation, ICG produced reactive oxygen species and heat, while PFOB provided supplemental oxygen and collagenase degraded the extracellular matrix, together contributing to enhanced antitumor efficacy. In melanoma models, this system significantly inhibited tumor growth and reduced HIF-1α levels. In conclusion, this study offers a novel strategy to increase the efficacy of PDT in the treatment of melanoma.