Abstract
Temoporfin (mTHPC) is approved in Europe for the photodynamic treatment of head and neck squamous cell carcinoma (HNSCC). Although it has a promising profile, its lipophilic character hampers the full exploitation of its potential due to high tendency of aggregation and a reduced ROS generation that compromise photodynamic therapy (PDT) efficacy. Moreover, for its clinical administration, mTHPC requires the presence of ethanol and propylene glycol as solvents, often causing adverse effects in the site of injection. In this paper we explored the efficiency of a new mTHPC formulation that uses human serum albumin (HSA) to disperse the photosensitizer in solution (mTHPC@HSA), investigating its anticancer potential in two HNSCC cell lines. Through a comprehensive characterization, we demonstrated that mTHPC@HSA is stable in physiological environment, does not aggregate, and is extremely efficient in PDT performance, due to its high singlet oxygen generation and the high dispersion as monomolecular form in HSA. This is supported by the computational identification of the specific binding pocket of mTHPC in HSA. Moreover, mTHPC@HSA-PDT induces cytotoxicity in both HNSCC cell lines, increasing intracellular ROS generation and the number of γ-H2AX foci, a cellular event involved in the global response to cellular stress. Taken together these results highlight the promising phototoxic profile of the complex, prompting further studies to assess its clinical potential.
Funder
Italian Association for Cancer Research
Fondazione Umberto Veronesi
Subject
Molecular Biology,Biochemistry
Reference71 articles.
1. Photodynamic Therapy for Squamous Cell Carcinoma of the Head and Neck: Narrative Review Focusing on Photosensitizers;Ibarra;Lasers Med. Sci.,2022
2. Global Cancer Observatory, International Agency for Research on Cancer, and World Health Organization (2022, October 15). Available online: https://gco.iarc.fr/.
3. Head and Neck Squamous Cell Carcinoma;Johnson;Nat. Rev. Dis. Primer,2020
4. Photodynamic Therapy of Head and Neck Cancers;Biel;Methods Mol. Biol.,2010
5. The Present and Future Role of Photodynamic Therapy in Cancer Treatment;Brown;Lancet Oncol.,2004
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