Liposomal formulations of magnesium sulfanyl tribenzoporphyrazines for the photodynamic therapy of cancer

Authors

Jaroslaw Piskorz, Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, PolandFollow
Dariusz T. Mlynarczyk, Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland
Wojciech Szczolko, Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland
Krystyna Konopka, Department of Biomedical Sciences, University of the Pacific, Arthur A. Dugoni School of Dentistry, 155 Fifth Street, San Francisco, CA 94103, USAFollow
Nejat Düzgüneş, Department of Biomedical Sciences University of the Pacific, 155 Fifth Street, San Francisco, CA 94103, USAFollow
Jadwiga Mielcarek, Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, PolandFollow

Lead Author Affiliation

Department of Biomedical Sciences

Introduction/Context/Diagnosis

Photodynamic therapy (PDT) is a treatment that uses light to activate a photosensitizer in the presence of oxygen, leading to the damage of targeted cells by the generation of reactive oxygen species. PDT is used to treat various cancers and cardiovascular, dermatological and ophthalmic diseases as well as different microbial and viral infections. The main drawbacks of currently used photosensitizers, including porphyrinoids, are poor aqueous solubility and the tendency to form aggregates. These issues have been addressed by developing drug delivery systems of which liposomes are considered one of the best and most promising. In this study, previously synthesized dendritic magnesium tribenzoporphyrazineswere incorporatedinto four types of liposomes

Methods/Treatment Plan

dendritic magnesium tribenzoporphyrazineswere incorporatedinto four types of liposomes containing either 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) as the zwitterionic lipids. The addition of either L-α-phosphatidyl-DL-glycerol (PG) or 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) imparted a negative or positive charge, respectively. Novel formulations were tested in oral squamous cell carcinoma cell lines (CAL 27, HSC-3) as well as cervical adenocarcinoma cells (HeLa).

Results/Outcome

Positively charged DOTAP : POPC

liposomes were the most effective carriers for all tested tribenzoporphyrazines. Calculated IC₅₀ values for DOTAP : POPC liposomes indicated that the incorporation of tribenzoporphyrazines into these liposomes can improve photocytotoxicity up to 50-fold compared to the free forms of the macrocycles. Oral cancer cells (CAL 27 and HSC-3) were more sensitive to liposomal photodynamic treatment than HeLa cells.

Significance/Conclusions

The efficiency of liposomes as carriers for tribenzoporphyrazines is dependent on both the compound used and the cells tested. Oral cancer cells CAL 27 and HSC-3 are more sensitive to photodynamic treatment than HeLa cervical adenocarcinoma cells. The appropriate liposomes can be used to deliver photosensitizers into oral cancer tumors or early mucosal lesions for non-invasive treatment employing light-guide-mediated illumination of the area.

Location

2nd floor clinic and reception waiting areas

Format

Poster