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Author Relats Camps, Marc |
Abstract Gene and oligonucleotide-based therapies are increasing for many applications, including the treatment of cancers. However, efficient intracellular delivery of these is very complicated. Biomolecules are very difficult to treat due to their large size, hydrophilic nature, and low stability. To increase the delivery efficiency of these macromolecules, non-viral polymeric nanoparticle delivery systems hold great promise. Among the numerous polymer cationic studied for this purpose, oligopeptide-modified poly (beta-aminoesters) (OMpBAEs) developed in the Materials Engineering Group (GEMAT) of IQS stand out for their high transfection capacity and low toxicity. Although selectivity can be adjusted to some extent, OM-pBAE polyplex transfection is remarkably promiscuous. In this work, we propose the use of different polymeric coatings to reduce promiscuity and incorporate peptides to target nanoparticles to cancer cells. As a starting point, the objective is to allow this selective delivery, it is an electrostatic poly (L-glutamic acid) PGA shown to reduce the transfection capacity of OM-pBAE polyplexes. Furthermore, we want to show that incorporating a peptide against the transferrin receptor, which is overexpressed in many cancer cells, allows recovery and even improvement of pBAE knot transfection levels. Furthermore, with the goal of further improving transfection, we explored two options for activating covalent and electrostatic coatings. In the covalent approach, an N- (2-hydroxy) propyl methacylamide (HPMA) is copolymerized with diacetone acrylamide (DAAM) with the aim of forming lysine-terminated imine linkages pBAE polyplexes. In the electrostatic approach, HPMA is copolymerized with N- (3-aminopropyl) methacrylamide (APMA), and the positive charges of APMA are converted to negative by reaction with citraconic anhydride. The pH sensitivity of this masked coating is demonstrated with a Kaiser colorimetric test. Together, this work lays the foundation for the development of pH-sensitive smart coatings that decrease the promiscuity of OM-pBAE and improve tumor selectivity. |
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Director Borrós i Gómez, Salvador |
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Degree IQS SE - Master’s Degree in Materials Science and Engineering |
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Date 2021-07-16
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