RESUMO
Liposomes have become successful nanostructured systems used in clinical practices. These vesicles are able to carry important drug loadings with noteworthy stability. The aim of this work was to develop iron oxide-loaded stealth liposomes as a prospective alternative for the treatment of lung cancer. In this study, citric acid iron oxide nanoparticles (IONPs-Ac) were synthesized and encapsulated in stealth liposomes. Their cytotoxicity and selectivity against lung tumor cells were assessed. Stealth liposomal vesicles, with relevant content of IONPs-Ac, named ferri-liposomes (SL-IONPs-Ac), were produced with an average size of 200 nm. They displayed important cytotoxicity in a human lung cancer cells model (A549 cells), even at low concentrations, whereas free IONPs-Ac displayed adequate biocompatibility. Nevertheless, the treatment at the same concentration of ferri-liposomes against HEK-293 cells, a normal human cell lineage, was not significantly cytotoxic, revealing a probable lung tumor selectiveness of the fabricated formulation. Furthermore, from the flow cytometry studies, it was possible to infer that ferri-liposomes were able to induce A549 tumor cells death through apoptosis/ferroptosis processes, evidenced by a significant reduction of the mitochondrial membrane potential.
RESUMO
Protein-polymer conjugates have achieved tremendous attention in the last few years, since their importance in diverse fields including drug delivery, biotechnology and nanotechnology. Over the past few years, numerous chemical strategies have been developed to conjugate different synthetic polymers onto proteins and great progress has been made. Currently, there are a handful of therapeutic polymer conjugates that have been approved by the FDA, while many hundreds of products are under extensive clinical trials and preclinical development phases. In this way, the development of novel techniques for conjugation, especially living radical polymerisation (LRP) has greatly enhanced the potential to broaden the scope of therapeutic conjugates. As a consequence, versatile techniques have developed, such as the 'grafting from' approach, which allows modifications of biomacromolecules at the atomic level, and subsequently preparing well-defined stimuli-responsive conjugates. These strategies present a unique perspective for therapy expansion of a new generation of 'smart' products with proprieties that can be finely controlled and tuned rather than just enhanced. This article highlights recent advances in the synthesis and application of protein-polymer conjugates by controlled radical polymerisation techniques, with special emphasis on stimuli-responsive conjugates on new applications in biomedical and pharmaceutical areas.