The ability to control the assembly and morphology of nanoscale materials in response to specific biomolecular stimuli is expected to have a significant impact in targeted drug delivery and advanced sensor design. A set of strategies are being developed in our laboratories at UC San Diego to incorporate enzymes, proteins, peptides and nucleic acids into novel polymeric synthetic materials with the aim of programming morphology and function. Below we highlight two projects ongoing in our laboratories.
Nucleic Acids as Programming Tools for the Nanoscale Morphology of Polymeric Materials
This project in advanced nanomaterials addresses one of the major challenges in chemistry and materials science, namely predictably setting the size and shape of a soft nanoscale object. The future of smart nanoscale drug delivery vehicles and indeed, self-healing and stimuli responsive materials in general, lies with materials capable of responding to their environment via well-defined and profound changes in nanoscale structure, shape and surface chemistry. Many current stimuli-responsive materials intended for these purposes rely on pH, light, and temperature for controlling their properties making them difficult to couple to biochemical stimuli. Inspired by the utility of DNA as an informational molecule in nanotechnology, we are developing DNA-encoded polymeric materials capable of in situ controlled, selective, reversible and user-defined shifts in morphology. The design is based on polymeric micelles formed from a novel set of amphiphilic DNA-brush copolymers. Utilizing the sequence selective recognition properties of DNA, and its performance as a substrate for selective enzymatic cleavage, information stored in the micelle shell can be read and manipulated in several modes causing dramatic changes in morphology and particle size. Most importantly, these changes manifest as changes in the functional properties of the materials.
Peptides and Enzymes as Regulators of Micellar Nanoparticle Morphology and Chemistry
In biology, stimuli-responsive multisubunit assemblies are ubiquitous, and mimicking these systems via synthetic approaches is of increasing interest. Interfacing such synthetic materials with biological systems is particularly promising for a range of biomedical applications including targeted drug delivery and molecular diagnostics. Within this class of materials are particles capable of changing morphology in response to stimuli. Enzymes are attractive and unique stimuli with great potential in this regard, as they propagate an amplified response via catalytic reactions, can be highly substrate specific, and have expression patterns sometimes associated with disease states. Nanoscale assemblies of block copolymer amphiphiles are well-suited for the development of functional, stimuli-responsive systems because changes in the chemical or physical nature of the amphiphile can lead to formation, destruction, or morphological transformations. In this work we seek to understand how enzymatic reactions can be used to manipulate micellar nanoparticle chemistry and morphology with a view towards a range of materials and biomedical applications where the shape and size of a soft nanoscale particle are critical to their function. One example of this type of material are polymeric amphiphiles in which the polar head group of the molecules consists of a brush of specially designed peptides. The peptides can be substrates for enzymes of interest, and therefore, resulting enzymatic reactions can be used to tune and switch the structure of the particles.