RESUMEN
Superparamagnetic iron oxide nanoparticles (SPIONs) have their use approved for the diagnosis/treatment of malignant tumors and can be metabolized by the organism. To prevent embolism caused by these nanoparticles, they need to be coated with biocompatible and non-cytotoxic materials. Here, we synthesized an unsaturated and biocompatible copolyester, poly (globalide-co-ε-caprolactone) (PGlCL), and modified it with the amino acid cysteine (Cys) via a thiol-ene reaction (PGlCLCys). The Cys-modified copolymer presented reduced crystallinity and increased hydrophilicity in comparison to PGlCL, thus being used for the coating of SPIONS (SPION@PGlCLCys). Additionally, cysteine pendant groups at the particle's surface allowed the direct conjugation of (bio)molecules that establish specific interactions with tumor cells (MDA-MB 231). The conjugation of either folic acid (FA) or the anti-cancer drug methotrexate (MTX) was carried out directly on the amine groups of cysteine molecules present in the SPION@PGlCLCys surface (SPION@PGlCLCys_FA and SPION@PGlCLCys_MTX) by carbodiimide-mediated coupling, leading to the formation of amide bonds, with conjugation efficiencies of 62% for FA and 60% for MTX. Then, the release of MTX from the nanoparticle surface was evaluated using a protease at 37 °C in phosphate buffer pH~5.3. It was found that 45% of MTX conjugated to the SPIONs were released after 72 h. Cell viability was measured by MTT assay, and after 72 h, 25% reduction in cell viability of tumor cells was observed. Thus, after a successful conjugation and subsequent triggered release of MTX, we understand that SPION@PGlCLCys has a strong potential to be treated as a model nanoplatform for the development of treatments and diagnosis techniques (or theranostic applications) that can be less aggressive to patients.
RESUMEN
Poly(ε-caprolactone) (PCL) is commonly used in devices for tissue reconstruction due to its biocompatibility and suitable mechanical properties. However, its high crystallinity and hydrophobicity do not favor cell adhesion and difficult polymer bioresorption. To improve these characteristics, the development of engineered scaffolds for tissue regeneration, based on poly(globalide-co-ε-caprolactone) (PGlCL) covalently bonded with N-acetylcysteine (PGlCL-NAC) was proposed. The scaffolds were obtained from polymer blends of PCL and PGlCL-NAC, using the electrospinning technique. The use of PGlCL-NAC allowed for the modification of the physical and chemical properties of PCL electrospun scaffolds, including an expressive reduction in the fiber's diameter, hydrophobicity, and crystallinity. All electrospun scaffolds showed no cytotoxicity against fibroblasts (McCoy cells). In vitro biocompatibility assays showed that all tested scaffolds provided high cell viability and proliferation in short-term (NRU, MTT, and nuclear morphology assays) and long-term (clonogenic assay) assays. Nevertheless, PGlCL-NAC based scaffolds have favored the survival and proliferation of the cells in comparison to PCL scaffolds. Cell adhesion on the scaffolds assessed by electronic microscopy images confirmed this behavior. These results suggest that the incorporation of PGlCL-NAC in scaffolds for tissue regeneration could be a promising strategy to improve cell-surface interactions and contribute to the development of more efficiently engineered biomedical devices.