Photodynamic therapy (PDT) is an anti-cancer treatment method, which uses the combined effect of a photosensitizing drug, light, and oxygen to cause selective damage to target tissue. The second generation photosensitizer (PS) 5,10,15,20-tetrakis(m-hydroxyphenyl)chlorin (m-THPC) is a clinically tested and commercially available drug. In order to develop advanced treatment modalities there is a need for improved drug delivery platforms. Hydrogels, investigated as effective drug delivery systems, can prevent PS aggregation and have ability to swell in aqueous media. Chitosan (CS), a natural polysaccharide, is a suitable biodegradable material for hydrogel formulation and has been used in pharmaceutical applications on account of its lack of toxicity and good biocompatibility. Herein, m-THPC was used as a starting point to obtain a library of compounds aimed at overcoming the PS’s limitations while maintaining its photophysical and clinical properties. Substitution, esterification and Sonogashira coupling reactions were employed to modify the m-THPC skeleton providing aldehyde and carboxylic acid moieties which served as a suitable synthetic handle for covalent cross-linking in the formation of CS hydrogels. Injectable, self-healing properties of hydrogels were confirmed by the rheological analysis. The tetrafunctionalized m-THPC derivatives, maintaining efficient singlet oxygen generation upon incorporation into hydrogels, are under ongoing in vitro evaluation against melanoma cancer cells (B16F10). Prepared hydrogel formulations are expected to allow for a local, injectable administration towards melanoma tumors, while preventing from systemic side effects related to the m-THPC treatment.

Covalently cross-linked tetrafunctionalized m-THPC chitosan hydrogels as delivery platforms.

ACS Spring Meeting 2021

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