Resumen de Gated mesoporous silica nanoparticles for biomedical applications
This PhD thesis entitled "Gated mesoporous silica nanoparticles for biomedical applications" is focused on the design and synthesis of novel nanodevices for sensing and therapeutic applications in clinical and environmental fields.
The first introductory chapter presented an overview of the different concepts related to nanotechnology, supramolecular chemistry, mesoporous silica nanoparticles (MSNs), and molecular gates.
Next, the general and specific objectives of this PhD thesis, that are addressed in the different experimental chapters, are presented.
The third chapter presented the design, synthesis, and characterization of a nanodevice for endotoxin detection in aqueous environments. The prepared nanodevice is based on mesoporous silica nanoparticles loaded rhodamine B and with its external surface functionalized with carboxylates. Pores are finally capped upon addition of cationic polymyxin B peptide. In the presence of endotoxin, polymyxin B is detached from the surface of the nanoparticles with subsequent rhodamine B release from the inner of the pores to the solution. This release generated a marked emission enhancement in solution which allow endotoxin detection. The obtained response was highly selective to endotoxin because other interfering agents such as arabinogalactan, ß-(1,3)-D-glucan, pectin, EDTA, glucose, GTP and dust were unable to induce pore opening and rhodamine B release. Besides, the system detects endotoxin with a limit of detection in the picomolar range.
The fourth chapter presented a nanodevice, based on mesoporous silica nanoparticles loaded with rhodamine B and capped with anionic curcumin, which is used for the selective and sensitive fluorogenic detection of human serum albumin (HSA). Again, in the presence of HSA, curcumin was detached from nanoparticles surface allowing rhodamine B release. Prepared nanodevice showed a highly selective response toward HSA with a limit of detection for HSA as low as 0.1 mg/mL in PBS (pH 7.4)-acetonitrile 95:5 v/v.
Chapter five focus on the design and synthesis of a nanodevice for the synergic release of linezolid antibiotic in the presence of Gram-negative bacteria. This nanodevice is based on the use of mesoporous silica nanoparticles (as inorganic support) with the pores loaded with linezolid and capped with the membrane disruptor polymyxin B through electrostatic interactions. When these particles enter in contact with Gram-negative bacterium, lipopolysaccharide (LPS) present in the cell membrane induces the detachment of polymyxin B, which acts as membrane permeator, from the nanodevice allowing linezolid release. Simultaneous release of linezolid and polymyxin B as a nanoformulation induced a marked reduction in the IC50 values for bacteria when compared to the values obtained using free linezolid and polymyxin B alone.
The sixth chapter is devoted to the discussion of the experimental results described in the previous chapters.
Finally, the seventh chapter of this PhD thesis, presented the main conclusions, derived from the experimental work, and future perspectives in the field of gated mesoporous silica nanoparticles for biomedical applications. We hope that the results achieved in this PhD thesis will open new research opportunities to develop advanced smart nanodevices as antimicrobial drugs
