Riassunto analitico
Glioblastoma multiforme (GBM) is a highly aggressive brain tumor, characterized by rapid progression, poor prognosis, and limited survival outcomes. Current therapeutic approaches, including surgical resection followed by radiotherapy and chemotherapy, often fail due to GBM’s invasive nature, the presence of the blood-brain barrier (BBB), and the tumor's resistance to conventional treatments. As such, there is a critical need for innovative treatment strategies that can effectively target and eradicate GBM cells. Gene therapy has emerged as a promising alternative, particularly by introducing therapeutic genes that can restore the function of tumor suppressor genes which are frequently mutated in GBM. This approach has the potential to directly address the genetic abnormalities driving GBM growth and therapy resistance.
This study aimed to develop and characterize polymeric nanoparticles (NPs) as non-viral vectors for efficient plasmid DNA (pDNA) delivery in GBM gene therapy.
Various polymers were selected for NP formulation, including chitosan and polyethyleneimine (PEI), which were chosen for their biocompatibility and ability to complex with negatively charged pDNA via electrostatic interactions. The NPs were further coated with Pluronic® F127 for PEGylation and functionalized with the F7 cell-penetrating peptide to enhance cellular uptake. NPs were synthesized in aqueous environments under controlled conditions, and their physicochemical properties were characterized using Dynamic Light Scattering (DLS).
In vitro validation using HEK-293 and U251-MG (GBM) cell lines demonstrated successful internalization and transfection efficiency of NPs. In addition, cytotoxicity assays confirmed the safety of the final formulation.
Besides the transfection of therapeutic genes was not tested within this study, NPs show potential as an efficient and biocompatible non-viral vector for gene therapy. The findings suggest that these NPs, with the appropriate functionalization and enhancements, could also provide a solid basis for upcoming in vivo studies.
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