CAREER: Responsive Biomimetic Strategies in Drug Delivery: Molecular Brush Oligomers

Johns Hopkins University, Baltimore MD

Investigators

Abstract

TECHNICAL ABSTRACT: This research explores the use of amphiphilic brush copolymers to build environmentally responsive filamentous nanostructures for targeted drug delivery applications. The objective of this proposal is to synthesize constructs that enhance delivery by controlling carrier-cell interactions through shape-dependent environmentally tunable mechanisms. The PI will design oligomers of molecular brushes containing environmentally responsive moieties along the backbone and between adjacent brushes to produce carriers of hydrophobic solutes with controllable spatial and/or temporal 3-D structure, surface chemistry, and mechanical properties. The biomimetic aspect of these constructs relies on the fact that they are designed after the segmental nature of secreted mucins. The programmable aspect targets their environmentally triggered de-oligomerization and conformational transitions. To address this scientific challenge the PI will utilize well-defined polymer synthesis and conjugation methods and engineer surface functionalization techniques. The specific objectives of this proposal are: (1) to design, synthesize, and characterize amphiphilic core-shell molecular brushes with pH-sensitivity and then carry out their oligomerization; (2) to study the hydrophobic collapse of molecular brush oligomers, solute loading, and the triggered shape change and de-oligomerization of brush filaments; and (3) to synthesize surface patterned particles from molecular brushes by the copolymerization of pre-assembled building blocks. NON-TECHNICAL ABSTRACT: The proposed research will provide valuable information regarding the design of new polymers inspired by nature. The knowledge gained through the completion of this project will provide us with a better understanding of the structure/property relationships of these building blocks and will allow us to use them in the context of other bioinspired materials applications. If successful, this project will advance drug-carrier design by harnessing the chemical flexibility and unique physical properties of stimuli-responsive polymeric biomaterials to control carrier-cell interactions across the micro-to-nano length scale. The broader impact of the proposed CAREER program will combine the PI's research interest in the development of 'intelligent' polymer-based biomaterials with an educational program targeted to generate interest in the field throughout the pre-undergraduate educational levels, particularly among under-represented student populations. By creating an engaging and inspiring research environment, the PI will seek to continually interest undergraduate and graduate students in the field of stimuli-responsive polymer systems and drug delivery. The nature of the proposed research should provide students with stimulating challenges across disciplines, a comprehensive education in polymer science from theoretical and experimental perspectives, and with the tools to address a problem with creativeness and a critical mindset.