A powerful paradigm for advanced cancer therapy combines delivery and imaging into one agent: so-called theranostic materials (for �therapeutic� and �diagnostic�). One potential platform for such an agent is nano- or microparticles consisting of porous silica, a well-characterized material with minimal toxicity and with great flexibility for chemical functionalization. Many theranostic systems, including those based on silica, depend on triggers from biologically-relevant stimuli to effect the release of a payload or the activation of some imaging modality. These stimuli include a decrease in pH in tumor stroma or the reducing conditions in intracellular environments.We have designed a set of universal, stimuli-responsive organoalkyoxysilanes that are cleaved under acidic or reducing conditions for use with silica theranostic agents. We have synthesized a number of acetal and disulfide linkers containing either an azide or a terminal alkyne, making them reactive in the popular, high-yielding �click� reaction of the Huisgen dipolar cycloaddition. We have tested several activated disulfides in the synthesis of our disulfide linker, as well as several routes of alkynylation, most notably with propargyl bromide and 4-pentyn-1-ol. Because many potential payloads are available with complementary click handles, our silanes allow for the facile functionalization of any silica theranostic agent with pH- or redox-cleavable payloads.We have characterized the novel linkers using NMR and FTIR spectroscopies and have immobilized the linkers to porous silica particles and characterized them by TGA. Also, we have tested the linkers' ability for triggered release using in vitro tests. Finally, we are also interested in fluorine-containing groups for use in 19F magnetic resonance imaging with �switch-on� imaging triggered by a biological stimulus. Thus, we have additionally developed a variety of cleavable and non-cleavable fluorine-containing alkoxysilanes for modifying silica particles with fluorine atoms.

Synthesis of stimuli-responsive linkers for use in silica multifunctional drug-delivery agents

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.