Responsive polymer assemblies show great promise in a range of applications, including drug delivery, sensing, and catalysis. Crucial to the elaboration of these systems is the development of polymers that undergo rapid, predictable, and reversible changes between assemblies with different sizes and structures. For applications involving encapsulation of other species within polymer vesicles, the development of more efficient encapsulation methods is also of great importance. To meet these challenges, the PI and co-workers have previously prepared temperature-responsive ABC triblock copolymers with poly(ethylene oxide) (PEO) as a hydrophilic block, poly(N-isopropylacrylamide) as a thermoresponsive block, and polyisprene as a cross-linkable hydrophobic block, which form assemblies that undergo large changes in size and shape around a critical temperature, however the reorganization of small assemblies (micelles of 20 nm diameter) into larger assemblies (vesicles of >100 nm diameter) at elevated temperatures was found to take several weeks. Recently, related copolymers with poly(butylene oxide-stat-ethylene oxide) responsive blocks, in which there are weaker interchain interactions in the absence of water, were found to undergo significant structural transformations within several hours. This research will probe the hypothesis that weakening interchain interactions in the dehydrated state is critical to increasing assembly transformation rate. This research will further the understanding of these block copolymer systems and their potential applications. Specifically, the PI and co-workers will investigate new hydrophilic-responsive-hydrophobic triblock copolymers, further probe possible structural transformations (e.g., micelle-to-worm-like micelle), more deeply investigate the kinetics of the assembly transformation process, and carry out encapsulation and release studies with block copolymer assemblies. The further study of these novel responsive systems offers the potential to expand and transform the applications of polymer-based nanostructures.
NON-TECHNICAL SUMMARY:
Nanometer-sized assemblies of polymer molecules show much promise in a range of applications, from the treatment of cancer and other diseases to the development of new sensory devices. This research will further our understanding of polymer assemblies that are designed to undergo specific changes in size and shape upon exposure to heat or other stimuli. In doing so, it will lay the groundwork for future efforts to use these materials in applications where the response to stimulus can be coupled to a specific application, such as release of a chemotherapy agent or the detection of specific molecules. This research will be carried out by graduate and undergraduate students as part of their scientific training and will involve collaboration with other researchers at Stony Brook University, Brookhaven National Laboratory, and Warwick University (UK). The PI will work through the State University of New York Louis Stokes Alliance for Minority Participation (SUNY LSAMP) program to recruit undergraduate students to participate in research in the chemistry department. Results of this work will be presented at internationally-attended scientific meetings and the PhD students involved in the project will maintain a website/blog through which they will be able to communicate their reflections on the project and the life of a scientific researcher to the general public.
Amphiphilic copolymers are long chain-like molecules in which part of the chain is hydrophilic and interacts strongly with water while the other part of the chain is hydrophobic and avoids interacting with water. The relative sizes of the hydrophilic and hydrophobic segments of the chain determine the size and shape of the aggregates that the polymers form in solution to maximize interactions of the hydrophilic components with water and to minimize the interactions of hydrophobic components with water. The research supported by this grant was designed to produce a better understanding of how amphiphilic polymers that have different ratios of hydrophilic to hydrophobic components at a low temperature than at a high temperature. In previous NSF-supported work, the investigators studied two triblock copolymer systems: poly(ethylene oxide)-block-poly(N-isopropylacrylamide)-block-polyisoprene (PEO-b-PNIPA-b-PI) and poly(ethylene oxide)-block-poly(ethylene oxide-stat-butylene oxide)-block-polyisoprene (PEO-b-PEOBO-b-PI). Each of these copolymers has a thermally responsive block—hydrophilic at lower temperatures and hydrophobic at higher temperatures—situated between a hydrophilic poly(ethylene oxide) (PEO) block and a hydrophobic polyisoprene (PI) block. At appropriate compositions, both copolymers were found to form small spherical micelles at room temperature and much larger vesicles at higher temperatures. The PEO-b-PNIPA-b-PI copolymer assemblies underwent this structural transformation very slowly (4 weeks), while the PEO-b-PEOBO-b-PI copolymer assemblies were found to grow much more rapidly (< 2 hours). Intellectual Merit: In this work, the investigators designed and studied a new class of triblock copolymers that was simpler to synthesize than the previously investigated systems and that was designed to probe the hypothesis that interactions between the central polymer blocks (PNIPA or PEOBO) of the polymer chains had a strong effect on how quickly the polymer assemblies could grow at higher temperatures. The new class of polymers, prepared by the versatile reversible addition-fragmentation chain transfer (RAFT) polymerization contained a central block incapable of hydrogen bonding to itself. Poly(ethylene oxide)-block-poly(N,N-diethylacrylamide)-block-poly(N,N-dibutylacrylamide) (PEO-b-PDEAm-b-PDBAm; Scheme 1) assemblies in water were found to undergo rapid transitions, as predicted, with spherical micelle-to-spherical vesicle and worm-like-micelle-to-spherical vesicle observed by electron microscopy and light scattering-based particle size measurements (Figure 1). More specifically, the project has validated the efficacy of RAFT polymerization for the preparation of PEO/alkylacrylamide block copolymers and for the incorporation of azide-functionalized monomers. Results obtained in this reporting period support our hypothesis that minimizing attractive interactions between responsive blocks can increase the rate of block copolymer assembly response. We have also found evidence of thermally-induced worm-like-micelle-to-vesicle transitions. Broader Impact. One post-doctoral researcher, six graduate students, three undergraduate students, and one high school student have been trained in research, mentoring, and communication skills through either partial or full participation in this project. The project has contributed to the field Polymer Chemistry and chemistry in general through the development of synthetic tools for the synthesis of stimuli-responsive block copolymers. It has also contributed to the scientific training of young researchers. The polymer synthesis methods that have been developed are generally simple enough that researchers in related disciplines (Materials Science, Chemical Engineering, etc.) will be able to use the synthetic protocols being developed. The improved understanding of how amphiphile assemblies respond to changes in solvent quality and temperature should also be of use to colloid scientists and soft matter physicists. The potential to control vesicle size and encapsulation efficiency through induced response in confinement could have a large impact on the development of drug delivery systems. The project promoted collaboration between researchers in the Department of Chemistry and the Department of Materials Science and Engineering at Stony Brook University and the Center for Functional Nanomaterials at Brookhaven National Laboratory (BNL). The sharing of resources (knowledge, characterization equipment, computational resources) between these groups is likely to impact future development of research infrastructure at Stony Brook and BNL. The PI gave several lectures to students on polymer chemistry with examples from this research in the graduate Organic Chemistry course at Stony Brook University (CHE 503) and at Ningbo University (China). The PI also reworked the Materials Chemistry course (CHE 518/378) at Stony Brook to include literature examples and topics related to block copolymer synthesis and self-assembly.
