Inclusion complex vs. conjugation of hydrophobic photosensitizers with β-cyclodextrin: Improved disaggregation and photodynamic therapy efficacy against glioblastoma cells.

Abstract

Self-aggregation of hydrophobic porphyrin-based photosensitizers (PSs) in aqueous biological environment decreases their bioavailability and in vivo therapeutic efficacy, which hampers their clinical use in photodynamic therapy (PDT). In the current study, we explore three new supramolecular systems based of hydrophobic PSs (i.e. 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP) or 5-(4-carboxyphenyl)-10,15,20-triphenylporphyrin (P1COOH)) non-covalently or covalently attached to β-CD. The two non-covalent solid inclusion complexes (β-CD)2/mTHPP and [(β-CD)/P1COOH]4 are prepared by a new co-precipitation@lyophilization combined method and the covalent conjugate β-CD-P1 by click chemistry. The binding type effect and effectiveness on the disaggregation in aqueous medium and in vitro PDT efficacy against glioblastoma cancer cells of PSs are investigated for the three β-CD/PS systems. The findings reveal a remarkable improvement of the disaggregation and in vitro PDT activity of these β-CD/PS systems compared to the free PSs, except for [(β-CD)/P1COOH]4 inclusion complex caused by J-type self-aggregation of the inclusion complex in tetrameric form. β-CD-P1 conjugate shows the higher in vitro PDT efficacy compared to the other β-CD/PS systems. Overall, the results indicate that the disaggregation in aqueous medium and in vitro PDT activity of hydrophobic PSs can be improved by their binding to β-CD and the covalent binding is the best approach.