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Author Balmori Pastor, Alba |
Abstract NPs have gained promise for its potential therapeutic applications as drug delivery systems. The common procedure for this purpose is dissolving, encapsulating, and finally adsorbing or adhering a drug on the NPs surface, avoiding the undesired damage to healthy cells and organs. In the same way, mesoporous silica nanoparticles (MSN) have recently attracted a lot of attention in the nanomedicine field due to their singular characteristics. However, the therapeutic efficiency of MSNs when used as drug delivery systems is often compromised by the pre-release of loaded drug molecules during the blood circulation and the lack of ability to do targeting. Considering these two problems, we propose in this doctoral Thesis the utilization of the widely known protein corona to avoid this premature release by fitting it into the pore. To achieve this, Human Serum Albumin-NP loaded with an antitumor drug for selective liver targeting MSN has been constructed. The main objective of this work is the development of a nanoparticle-protein complex capable of an efficient delivery of a therapeutic drug. This complex should simultaneously avoid premature release and be able to do liver targeting both by effect of the PC. To reach this, first of all the synthesis of MSNs has been optimized, in order to obtain MSNs reproducible and with defined properties. Then, the corresponding characterization of their physicochemical traits showed that through the design of a DOE it is possible to elucidate which parameters have a higher influence on MSN synthesis. Furthermore, it has been here demonstrated that a qualitative and quantitative determination of the protein corona through an innovative use of analytical equipment is possible, the nanoDSC and ITC. This allows the deepening in the PC knowledge and control. It has also been assessed the effect of the protein corona in the release profile of an anti-tumor drug. Finally, the protein corona has been shown to provide a more sustained release of the drug to a liver tumor cell line, without affecting cell viability. In conclusion, results have shown that the relationship between the pore size and the protein size in HSA-MSN systems determine the system’s application. In this work it has been proposed the PC engineering according to the size ratio between the pore and the protein to use the same proteins that form the protein corona as gatekeepers while targeting the desired organ. |
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Director Borrós Gómez, Salvador |
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Department IQS SE - Bioenginyeria |
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Date of defense 2019-10-28
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