CAREER: Implementing a Stealth-to-Targeting Switch in Model Colloidal Carriers

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ID: MPS/DMR/BMAT(7623) 0847436 PI: Milam, Valeria ORG: Georgia TechTitle: CAREER: Implementing a Stealth-to-Targeting Switch in Model Colloidal CarriersThis award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).INTELLECTUAL MERIT: This proposal is concerned with implementing a dynamic stealth-to-targeting switch in model colloidal carriers. Specific motivation for this work lies in the therapeutic limitations of current drug delivery vehicles possessing either stealth or targeting capabilities. By incorporating a dynamic stealth-to-targeting switch, the proposed research has the potential to pave the way for a new generation of drug carrier systems that fully realize their therapeutic index through dramatic improvements in both circulation time and desired targeting abilities for injured, malignant, or diseased tissue. To implement a finely controlled transition between stealth and targeting states, the proposed approach employs DNA as dynamic macromolecular linkers initially to mask, and then to reveal targeting ligands on model colloidal carriers. The central aim is to tailor the timing of DNA-mediated targeting events through directed hybridization events of DNA strands immobilized on the carrier surface. The challenge lies in controlling the stability and interactions of DNA in order to tailor the kinetics and extent of carrier ?activation.? To address this challenge, the proposed work will explore sequence characteristics, such as affinity differences between various oligonucleotide strands, to induce particular structural changes in the DNA strands and thereby modulate ligand presentation in a model carrier system. BROADER IMPACTS: The integrated education plan involves initiatives geared towards both high school students and engineering college students. The motivation for this plan lies in the need to (1) increase young students? exposure and interest in engineering, particularly to materials science and engineering (MSE) and (2) train engineering students to address the synergistic roles of materials and biological systems in bio-related materials applications. The first part of the educational plan involves developing and implementing a Materials Science and Technology (MST) course in a local high school. The objective of this laboratory-intensive course is to physically and intellectually engage young students in reinforcing and applying fundamental scientific and engineering principles using materials as a practical learning tool. A series of experiments on various classes of materials, including biomaterials, will be incorporated into the course topics. The target audiences for this hands-on, minds-on educational approach are (a) underrepresented groups in engineering for whom pre-university educational initiatives would help attract them to pursue degrees and careers in engineering and (b) the at-risk population of high school students who often possess the capability, but lack the motivation to take upper level, college preparatory courses in science and math. The teaching modules will be made freely available for public distribution through the MSE website at GA Tech. The second part of the educational plan involves developing MSE courses to address the structure and properties of both the biological and materials systems at biological-material interfaces. The objective is to extend a central paradigm in MSE ? structure-property relationships ? to include biological systems, consistent with ongoing efforts in our MSE program aimed at integrating biorelated topics in the curriculum.