Nature versus nurture in cellular behavior and disease.

Abstract

This project pursued two complementary, interrelated goals: 1) the incorporation of individual or groups of bacterial, fungal, or mammalian cells within novel three-dimensional (3D) cell-built or lithographically defined matrices that provide an engineered chemical and physical background to inform cells and direct their behavior; and 2) the development of two classes of targeted nanoparticle delivery platforms, protocells (porous nanoparticle supported lipid bilayers) and virus-like particles (VLPs), which could be selected against dormant/drug resistant/metastatic cells and selectively deliver multicomponent cargos (cocktails) to this recalcitrant population. This project provided a unique means to understand environmental influences on cellular behavior, in particular, dormancy, drug resistance, metastasis and 4 nanoparticle toxicology. It enabled the development of new targeting and drug delivery strategies designed to selectively attack and kill dormant and drug resistant cells, thereby reducing a significant reservoir of human disease. It established the scientific basis for creating new classes of cell based sensors, and it will provide a platform in which to understand nanoparticle toxicology in 3D environments, which better represent in vivo conditions. ACKNOWLEDGMENTS

Improved Efficacy and Reduced Toxicity Using a Custom-Designed Irinotecan-Delivering Silicasome for Orthotopic Colon Cancer

“…First, the support provided by the mesoporous silica core allows improved stability of the LB compared to that of the liposome. 14,[27][28][29]70 This stability improvement is reflected by prolonged circulatory half-life. Second, the porous structure of the coated MSNP provide a large surface area for drug packaging against the side walls of the pores as result of electrostatic and van der Waals interactions.…”

“…14 MSNPs are excellent carriers due to high biocompatibility, large surface area, tunable particle/pore sizes and tunable surface functionalization. 14,[25][26][27][28][29][30][31][32][33][34][35][36][37] It was also demonstrated that the MSNPs are biodegradable to silicic acid that is eliminated via urinary and fecal secretion in mice. [38][39][40] Since the improved efficacy of our lipid bilayer (LB)-coated MSNP carrier, a.k.a.…”

Sequence Multiplicity within Spherical Nucleic Acids

“…Delivering multiple entities on the same particle to immune cells is beneficial over administration of simple mixtures of the individual components, because the nanoparticle scaffold allows for delivery of programmed ratios of each component to the same target cell. 21,22 In this study, we incorporated two physically (e.g., structural features) and chemically (e.g., backbone chemistry) distinct oligonucleotide sequences, CpG-A (ODN 1585) and CpG-B (ODN 1826), into LSNAs (Scheme 1) to study the intracellular trafficking of the SNAs and their downstream activation of DCs.…”