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Autor
Martín Rosco, Raúl
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Abstract
Lung cancer, one of the most common causes of cancer death in the world, continues to grow year after year; being the first cause of death in men and the second in women. Despite the wide variety of current treatments: surgery, radiation therapy, chemotherapy, targeted therapy, and immunotherapy; it is not possible to improve the life expectancy of patients, making continuous improvement of these treatments essential.
Gene therapies currently represent one of the most important areas in the approach to this tumor. This therapy uses genetic material to act as a therapeutic agent for silencing specific genes for cancer development. To transport nucleic acids to targeted cells, the use of vectors is necessary. In order to make this treatment effective, vectors must comply with two fundamental principles: i) protect genetic material against nucleases that are responsible for catalyzing the breakdown of phosphodiester bonds in nucleic acids, ii) transfect selectively targeted cells.
The great limitation of this therapy is that only 0.7% of the dose administered using nanoparticles by parental route (usually intravenous), manages to reach the target cells in vivo due to the numerous biological barriers that nanoparticles must overcome.
The challenge of this project focuses on formulating nanomotors that may be capable of crossing a mucosa layer, as a biological barrier, thus increasing its effectiveness and allowing the use of the inhaled route for the administration of genetic material for the treatment of lung cancer. Specifically, polymeric nanoparticles of poly(β-amino ester)s modified at their ends with oligopeptides have been formulated to act as non-viral vectors by joining them with biocatalyst (particularly catalase) to be able to be propelled thanks to hydrogen peroxide, a chemical substance produced by lung cancer cells, generating greater motion of nanomotors, allowing the crossing of the lung mucosa and greater internalization in the cells. With the present work, the project’s proof of concept has been established: for the first time, catalase has been introduced into nanoparticles and its biocompatibility and mobility have been demonstrated.
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