Browsing by Author "Pereira, Mariana Franco"
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- Development of novel nanoplatforms for the imaging and targeting of breast tumour microenvironmentPublication . Pereira, Mariana Franco; Maia, Ana Teresa; Mendes, BárbaraBreast cancer is the most diagnosed neoplasia in the world and affects millions of women each year. Despite being the type of cancer with the greatest selectivity of treatments, these lead to a wide range of side effects. Gene therapy has emerged as a new therapeutic approach for the treatment of various diseases. This therapy involves transferring genes or regulatory sequences into target cells. This can modify or inhibit the gene expression, improving the treatment of hereditary or acquired diseases. In this work polymeric nanoparticles were developed due to their excellent properties, including the ability to protect genetic material from degradation by nuclease, low toxicity, biocompatibility, biodegradability, and high stability. Polyplexes were produced and characterized as a subclass of polymeric nanoparticles, regarding their physicochemical properties (size, polydispersity index and surface charge), cell viability and transfection efficiency in 2D and 3D cell cultures. Polyplexes when complexed with nucleic acids (pDNA and pDNA-miR-125b) had a small size and positive surface charge at N/P ratio of 20. Regarding complexation with miR-125b, there is the formation of large nanoparticles in the same ratio. The cell viability analysis showed that the polyplexes were not toxic. Transfection assays demonstrated that polyplexes are more efficient at delivering miR-125b to BC cells in 2D. Transfection efficiency was highest in the MDA-MB-231 cells with 88% of transfection. The results of the expression of miR-125b showed a transient increase in its expression levels, contributing to the inhibition of proliferation and cell migration of BC cells. The results of the incubation of the polyplexes in the breast cancer spheroids showed low transfection efficiency, which can be related to the morphology of the spheroids. In conclusion, the S2 polyplexes proved to be an excellent nanoparticle for delivering miR-125b in breast cancer cells, representing a new potential therapeutic agent. Future testing on 3D spheroid models can include using PAMAM nanoparticles as the delivery system or improving the functionalization of S2 polyplexes to increase transfection efficiency and, consequently, the expression levels of miR-125b.