Supramolecular strategies as well as combinatorial approaches have been proposed to improve cancer therapeutics. In this work, we investigated the encapsulation of the photosensitizer acridine orange (AO) and the chemotherapeutic drug oxaliplatin (OxPt) in cucurbit[8]uril (CB[8]), and tested their effect both separate and combined on tumoral cells cultivated in vitro. Binding constants and enthalpies of reaction for the AO@CB[8], (AO) 2 @CB[8] and OxPt@CB[8] complexes were determined by isothermal titration calorimetry. In the case of AO, a negative cooperativity for the binding of the second AO molecule was found, in agreement with previous fluorescence titration data. We show herein that the AO@CB[8] complex was effectively incorporated within the cells and showed important phototoxicity, while the OxPt@CB[8] complex was cytotoxic only at long incubation times (24 h). Pre-treatment of the cells with the OxPt@CB[8] complex for 24 h inhibited any photodynamic action by the later treatment with the AO@CB[8] complex. However, when both complexes were co-incubated for 90 min, the combined cytotoxicity/phototoxicity was superior to any of the treatments individually. A cooperative effect was identified that added up to an extra 30% cytotoxicity/phototoxicity. The results point to an interesting system where a photosensitizer and chemotherapeutic drug are co-encapsulated in a macrocycle to develop chemophototherapy applications.

Experiments and theoretical calculations by density functional theory (DFT) have been carried out to examine a self-sensitized type I photooxidation of toluidine blue O (TBO+). This study attempts to build a connection between visible-light photolysis and demethylation processes of methylamine compounds, such as TBO+. We show that controlled photoinduced mono- and double-demethylation of TBO+ can be achieved. The kinetics for the appearance rate of the mono-demethylated TBO+ and the double-demethylated TBO+ were found to fit pseudo-first-order kinetics. DFT calculations have been used to examine the demethylation of TBO+ and included N,N-dimethylaniline as a model compound for TBO+. The results show an oxygen-dependent demethylation process. The mechanism for the sequential methyl loss is proposed to be due to H • or e–/H+ transfer to 3TBO+* followed by a reaction of TBO+• with O2, yielding a C-peroxyTBO+• intermediate. Instead of aminyl radical peroxyl formation, i.e., N-peroxyTBO+• , the C-centered peroxyTBO+• is favored, that upon dimerization (Russell mechanism) leads to dissociation of formaldehyde from the methylamine site.

No abstract

Direct FXa inhibitors are an important class of bioactive molecules (rivaroxaban, apixaban, edoxaban, and betrixaban) applied for thromboprophylaxis in diverse cardiovascular pathologies. The interaction of active compounds with human serum albumin (HSA), the most abundant protein in blood plasma, is a key research area and provides crucial information about drugs’ pharmacokinetics and pharmacodynamic properties. This research focuses on the study of the interactions between HSA and four commercially available direct oral FXa inhibitors, applying methodologies including steady-state and time-resolved fluorescence, isothermal titration calorimetry (ITC), and molecular dynamics. The HSA complexation of FXa inhibitors was found to occur via static quenching, and the complex formation in the ground states affects the fluorescence of HSA, with a moderate binding constant of 104 M−1. However, the ITC studies reported significantly different binding constants (103 M−1) compared with the results obtained through spectrophotometric methods. The suspected binding mode is supported by molecular dynamics simulations, where the predominant interactions were hydrogen bonds and hydrophobic interactions (mainly π–π stacking interactions between the phenyl ring of FXa inhibitors and the indole moiety of Trp214). Finally, the possible implications of the obtained results regarding pathologies such as hypoalbuminemia are briefly discussed.

Photodynamic therapy of cancer (PDT) is a therapeutic technique, minimally invasive, which is currently used to treat cancerous lesions and tumors that have been in the spotlight for its potential over the recent decades. Nonetheless, PDT still needs further development to become a first-option treatment for patients. This review compiles recent progress in several aspects of the current research in the constantly growing area of PDT to overcome the main challenges as an attempt to serve as a guide and reference for newcomers into this research area. This review has been prepared to highlight the use of chemical modifications on photosensitizers to improve their solubility, photostability, selectivity and phototoxicity. Additionally, the use of liposomes and cavitands as drug delivery systems to aid in the biodistribution and bioaccumulation of photosensitizers is presented. Also, the combination of PDT with chemotherapy or immunotherapy as an option to boost and improve treatment outcomes is discussed. Finally, the inhibition of antioxidant enzymes as a strategy for a synergistic effect to ameliorate the performance of the photosensitizers in PDT is presented as an alternative for future researchers.