I. Hydrophobic nanoporous silica particles for biomedical applications. II. Novel approaches to two-dimensional correlation spectroscopy

Abstract

Many highly effective drugs display serious side-effects. To limit them, one can contain the drug in tiny containers, which are subsequently delivered toward targets inside the body. The entrapment of drug molecules prevents them from coming in contact with and thus causing damage to normal cells. Inherently, it is difficult to reach 100% efficiency of drug trapping and release when employing physical caps to seal the vehicles. Instead, we propose drug trapping inside the nanopores of hydrophobic silica particles by "hydrophobic trapping". This phenomenon is associated with the repulsive "force field" generated inside nanometer-sized hydrophobic channels that completely prevents aqueous solutions from entering the channels. We demonstrate the excellent trapping efficiency using C18-modified silica particles with 10 nm pores and the anticancer drug doxorubicin.The major challenge in using hydrophobic particles in biological applications is their tendency to cluster in aqueous media. To overcome it, we use surfactants as solubilization means. We have developed protocols that effectively solubilize the outer surface of the particles while preventing surfactant micelles from entering nanopores.Consequently, particles become well-dispersible in aqueous solutions, with the preloaded drug safely contained inside nanopores.Nanomaterials exhibit heterogeneity on their surfaces that impact their functional applications. Although techniques such as atomic force microscopy are great tools for studying nanomaterials with their excellent spatial resolution, they cannot probe the inner surface of porous structures. We have established a method of single-molecule ratiometric imaging that is currently the only technique able to provide the nanopolarity of adsorption sites located on the pore surface. We analyze the polarity distribution of adsorptions events for the solvatochromic probe Nile Red at the C18/acetonitrile interface and discover at least two different populations of adsorption sites. One of them corresponds to the polarity of surface silanol groups while the other sites have a polarity consistent with the environment inside the C18 organic layer. We also discover an additional adsorption mode situated at a polarity higher than exposed silanol surface that could presumably be linked to a different ionization state of the silanol groups.We are developing a method for resolving spectra of complex samples using twodimensional hetero-correlation spectroscopy by correlating the intensity fluctuations in optical spectra to those of completely separated peaks in analytical separations. We demonstrate this methodology for fluorescence spectra and electrophoregrams of mixtures anthracene-pyrene. All the individual vibronic features that overlap in mixtures are cleanly extracted in cross-sections of the two-dimensional asynchronous spectrum.Abstract Approved: ____________________________________ Thesis Supervisor ____________________________________

Biomedical applications of mesoporous silica particles

“…These cell viabilities against free doxorubicin are typical of the HEC50CO and CT26 cell lines [87,93,98,99]. The estimated release of doxorubicin from the nanoparticles is less than 10 µg/mL (Table 4- Hydrophobic trapping is the ability to efficiently prevent leaking of the loaded molecules by excluding aqueous solvent from the pores when the particles are suspended in an aqueous phantom matrix such as agar [103,113,114]. This trapping is experimentally simple.…”

“…To overcome the hydrophobic nature of the outer surface of the particles without releasing the loaded molecules, loaded particles were coated with sodium dodecylsulfate (SDS), selectively solubilizing the outer surface while keeping the pores dry. Immediate vortex mixing upon addition of the particles to SDS solutions in concentrations near the critical micellar concentration, 8 mM, generated a thick foam layer that incorporated the particles and accumulated on top of the liquid [113]. This [113].…”

“…Immediate vortex mixing upon addition of the particles to SDS solutions in concentrations near the critical micellar concentration, 8 mM, generated a thick foam layer that incorporated the particles and accumulated on top of the liquid [113]. This [113].…”

“…A schematic close-up of the mouth of a pore on a silica particle (beige) coated with a layer of C18(gray) showing the loading and hydrophobic trapping of a fluorophore (red stars) with an organic loading solvent (yellow) and an aqueous suspension medium (orange). Modified from[113].loaded molecule and the vessel wall or a physical plug inserted in the mouth of the pore -hydrophobic trapping is accomplished simply; no additional synthetic step is necessary, nor does trapping require chemical or mechanical means, which could alter the optical properties.A second requirement for developing a robust optical methodology is uniformity of the tissue phantom samples that are used to calibrate an optical device. Two specific barriers to the generation of a uniform tissue phantom have been identifieddistribution of loaded molecules in the mesopores and dispersal of hydrophobic particles in agar.…”

“…foam layer remained stable even on the time scale of months and could be reformed multiple times after resuspension in the SDS solution. The vortex mixing method is contrasted with sonication of the particles in an SDS solution which induces wetting of the pores, and subsequently, the particles in those samples sediment out of suspension (Figure 5-10).Both the concentration of the SDS solution and the immediate initiation of vortex mixing is critical to the formation of the foam layer[113]. Surfactant concentrations higher than approximately 20 mM induce pore wetting and cause the particles to sediment.…”