Bioconjugates of Toluidine Blue Derivatives with Human Serum Albumin and Their Complexes with Cucurbit[7]uril as Drug Delivery Vehicles for Photodynamic Therapy.

Photodynamic therapy (PDT) is a promising cancer treatment. The present work used two toluidine blue O (TBO) derivatives covalently conjugated to human serum albumin (HSA) as a drug delivery system and bound to cucurbit[7]-uril (CB[7]) as a protective nanocapsule in order to study their effect of cellular uptake and phototoxicity in HeLa cells. This study explored covalent and noncovalent interactions with the delivery systems, including HSA-PS@CB[7] complexes, to optimize PDT efficacy. Supramolecular complexes between TBO derivatives and CB-[7] exhibited high binding affinities, significantly improving the photophysical properties of the photosensitizers. In vitro studies in cancer cells demonstrated that HSA covalently bound to TBO derivatives led to significant increases in cellular uptake and was strongly influenced by the type of conjugation (disulfide bond versus thia-Michael adduct). The results suggest that combining the properties of HSA as a carrier and CB[7] as a protective nanocapsule could be exploited for improved PDT applications.