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New micro three-dimensional (3D) scaffolds using biobased unsaturated polyesters (UPs) were prepared by microstereo-thermal-lithography (μSTLG). This advanced processing technique offers indubitable advantages over traditional printing methods. The accuracy and roughness of the 3D structures were evaluated by scanning electron microscopy and infinite focus microscopy, revealing a suitable roughness for cell attachment. UPs were synthesized by bulk polycondensation between biobased aliphatic diacids (succinic, adipic and sebacic acid) and two different glycols (propylene glycol and diethylene glycol) using fumaric acid as the source of double bonds. The chemical structures of the new oligomers were confirmed by proton nuclear magnetic resonance spectra, attenuated total reflectance Fourier transform infrared spectroscopy and matrix assisted laser desorption/ionization-time of flight mass spectrometry. The thermal and mechanical properties of the UPs were evaluated to determine the influence of the diacid/glycol ratio and the type of diacid in the polyester's properties. In addition an extensive thermal characterization of the polyesters is reported. The data presented in this work opens the possibility for the use of biobased polyesters in additive manufacturing technologies as a route to prepare biodegradable tailor made scaffolds that have potential applications in a tissue engineering area.

This manuscript reports the synthesis of a new cationic block copolymer based on poly[2-(dimethylamino)ethyl methacrylate] and poly(β-amino ester) from different polymerization strategies. For the first time, it is proposed a triblock copolymer based only on cationic segments, aiming a high biocompatibility, enhanced buffering capacity and stimuli-responsive character in a single structure. The new block copolymer successfully condensed the plasmid DNA into nanosized polyplexes. The polyplexes were tested in two different cell lines revealing ∼4-fold and ∼6-fold (in HeLa cells), and ∼11-fold (in COS-7 cells) higher transgene expression than branched PEI and TurboFect™, respectively. These results show that this new block copolymer is a promising candidate to be used as a polymeric non-viral vector.

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Background: Hepatocellular carcinoma (HCC) is one of the main causes of cancer-related death. Sorafenib, which is the first-line therapy for this disease, is associated with reduced therapeutic efficacy that could potentially be overcome by combination with selumetinib. In this context, the main goal of this work was to develop a new nanosystem, composed of a polymeric core coated by a lipid bilayer containing the targeting ligand GalNAc, to specifically and efficiently co-deliver both drugs into HCC cells, in order to significantly increase their therapeutic efficacy. Methods: The physicochemical characterization of hybrid nanosystems (HNP) and their components was performed by dynamic light scattering, zeta potential, matrix-assisted laser desorption ionization -time of flight mass spectroscopy, and transmission electron microscopy. Cellular binding, uptake and specificity of HNP were evaluated through flow cytometry and confocal microscopy. The therapeutic activity was evaluated namely through: cell viability by the Alamar Blue assay; cell death by flow cytometry using FITC-Annexin V; caspases activity by luminescence; mitochondrial membrane potential by flow cytometry; and molecular target levels by Western blot. Results: The obtained data show that these hybrid nanosystems present high stability and loading capacity of both drugs, and suitable physicochemical properties, namely in terms of size and surface charge. Moreover, the generated formulation allows to circumvent drug resistance and presents high specificity, promoting great cell death levels in HCC cells, but not in non-tumor cells. This potentiation of the antitumor effect of co-loaded drugs was carried out by an increased programmed cell death, being associated with a strong reduction in the mitochondrial membrane potential, a significant increase in the activity of caspases 3/7 and caspase 9, and much greater number of annexin V-positive cells. Conclusion:The developed formulation resulted in a high and synergistic antitumor effect, revealing a translational potential to improve therapeutic approaches against HCC.