Magnetoliposomes Based on Magnetic/Plasmonic Nanoparticles Loaded with Tricyclic Lactones for Combined Cancer Therapy.

Liposome-like nanoarchitectures containing manganese ferrite nanoparticles covered or decorated with gold were developed for application in dual cancer therapy, combining chemotherapy and photothermia. The magnetic/plasmonic nanoparticles were characterized using XRD, UV/Visible absorption, HR-TEM, and SQUID, exhibiting superparamagnetic behavior at room temperature. The average size of the gold-decorated nanoparticles was 26.7 nm for MnFe2O4 with 5-7 nm gold nanospheres. The average size of the core/shell nanoparticles was 28.8 nm for the magnetic core and around 4 nm for the gold shell. Two new potential antitumor fluorescent drugs, tricyclic lactones derivatives of thienopyridine, were loaded in these nanosystems with very high encapsulation efficiencies (higher than 98%). Assays in human tumor cell lines demonstrate that the nanocarriers do not release the antitumor compounds in the absence of irradiation. Moreover, the nanosystems do not cause any effect on the growth of primary (non-tumor) cells (with or without irradiation). The drug-loaded systems containing the core/shell magnetic/plasmonic nanoparticles efficiently inhibit the growth of tumor cells when irradiated with red light, making them suitable for a triggered release promoted by irradiation.

Porphyrin dye into biopolymeric chitosan films for localized photodynamic therapy of cancer.

Porphyrins and some of its derivatives are well known and widely used as photosensitizers (PSs) for Photodynamic Therapy of Cancer (PDT). The present study regards the characterization and evaluation of a synthesized asymmetric porphyrin dye in solution to be used as PS for PDT. This molecule was also incorporated into biopolymeric films composed by chitosan, polyethylene glycol (PEG) and gelatin in order to overtake some of the disadvantages inherent to the PS, but more important, to evaluate the potential of a system composed by the porphyrin/biopolymer to be applied as localized therapeutic agents. FTIR spectroscopy showed a strong interaction between the polymers involved in the preparation of the films under study: film 1: chitosan, film 2: chitosan/PEG and film 3: chitosan/gelatin. Photochemical studies were performed for the dye in solution and into the three different biopolymeric films. Ground state absorption showed the characteristic bands of these kinds of dyes in solution and also incorporated into the films. The films composed by porphyrin/chitosan and porphyrin into chitosan/gelatin, revealed the presence of non-emissive aggregates exhibiting a strong quenching effect in the fluorescence intensity, quantum yields and lifetimes. In this way, the system composed by the porphyrin incorporated into the chitosan/PEG film presents the best fluorescence quantum yield and lifetime. The transient absorption spectra were obtained for all the systems indicating the formation of an excited triplet state of the porphyrins following excitation, which takes special importance in the generation of phototoxic species namely singlet oxygen. Singlet oxygen quantum yields were also determined and the results obtained were very promising for the dye in solution but also for the dye into the different substrates. The release of the dye from the three different films onto a buffer solution was evaluated and we conclude that after a few days the dye was completely released by the substrates in acidic conditions. Confocal microscopy was used for the determination of the intracellular localization of the compound under study onto HeLa cells (human cervical cancer cells line). The evaluation of the PSs anticancer activity assumes special importance for PDT studies. The system should be less toxic in the dark and more active when irradiated, therefore, toxicity in the dark and phototoxicity studies onto HeLa cells were performed.

A new antitumoral Heteroarylaminothieno[3,2-b]pyridine derivative: its incorporation into liposomes and interaction with proteins monitored by fluorescence.

The fluorescence properties of the new potent antitumoral methyl 3-amino-6-(benzo[d]thiazol-2-ylamino)thieno[3,2-b]pyridine-2-carboxylate in solution and when encapsulated in several different nanoliposome formulations were investigated. The compound exhibits very reasonable fluorescence quantum yields and a solvent sensitive emission in several polar and non-polar media, despite not being fluorescent in protic solvents. Fluorescence anisotropy measurements of the compound incorporated into liposomes revealed that this thienopyridine derivative can be carried in the hydrophobic region of the lipid membrane. Liposome formulations including this antitumor compound are nanometric in size, with a diameter lower than 130 nm and generally low polydispersity, and are promising for future drug delivery developments. The interaction of the compound with bovine serum albumin (BSA) and the multidrug resistance protein MDR1 was monitored by FRET, the compound acting as an energy acceptor. It was observed that the drug had a lower interaction with the MDR1 protein than with the native form of BSA, which is an important result regarding applications of this antitumoral drug.

Di(hetero)arylamines in the benzo[b]thiophene series as novel potent antioxidants.

The damaging consequences of oxidative stress are known to be involved in several pathologies. So, the development of new drugs that can aid cells to cope with excessive levels of free radicals still assumes great relevance. Here, we investigated the antioxidant properties of four novel di(hetero)arylamines (named MJQ1, MJQ3, MJQ4 and MJQ5), sharing a common benzo[b]thiophene nucleus (an indole analogue), against oxidative damage induced to H9c2 myoblasts. Cell proliferation, evaluated by the sulforhodamine B assay, was not compromised by the presence of any of these compounds for concentrations below 50 µM (at 24 h) and 1 µM (72 h). Moreover, all of them showed a dose-dependent protective effect against tert-butylhydroperoxide (t-BHP)-induced cell death for concentrations in the nanomolar range. Their ability to scavenge free radicals seems to account for their protective effects, as they were able to prevent almost completely, at 25 nM, t-BHP-induced intracellular ROS formation, assessed by DCF fluorescence. Furthermore, their relatively high partition coefficient values are indicative of their ability to easily permeate lipid membranes and act intracellularly. Additionally, these novel diarylamines led to a reduction, between 60-70%, of the amount of DNA strand breaks induced by t-BHP, evaluated by the Comet assay, and lipid peroxidation (TBARS assay) induced by the oxidant pair ascorbate/iron. In all these parameters, which show their ability to prevent the oxidation of the main biomolecules, their protective role was superior to the traditional antioxidant Trolox. Although the mechanisms underlying the action of these diarylamines are currently under investigation, the data obtained so far reveals their high pharmacological potential as antioxidant molecules.