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. Together, these efforts involve a concerted effort to develop bioresponsive, and bioactive chemical systems through innovations in synthesis and characterization of dynamic systems at multiple length and time scales.
Advanced Autonomic Materials
Biomolecules for Programming Nanomaterials
The development of methods for programming nanomaterials to perform complex changes in structure and function in response to environmental cues. This has lead to the design and implementation of novel DNA- and peptide-programmed micellar nanoparticles that can be deployed for sense-and-response applications. This program has formed the backbone of our group's efforts to establish techniques for building complexity into nanomaterials through robust methodologies in materials science and polymer chemistry. It also has as one of its key goals, the development of novel characterization methods for analysis of nanomaterials in complex milieu from biological fluids, to organs to environmental samples. Moreover, we are increasingly interested in the characterization of nanoparticles undergoing controlled switches and changes in structure and function in a dynamic fashion. Elucidation of dynamics will be the next frontier for this class of functional material.
UCSD Bioautocatalysis Team: AFOSR Sponsored Program
Collaboration: Burkart, Gilson, Kubiak, Tezcan (UCSD)
The development of strategies for evolving functional synthetic and semi-synthetic biocatalysts and functional, complex nanomaterials. This is a multi-disciplinary team effort to establish new paradigms for the discovery of function at the nanoscale by deploying machine learning, screening and design. Targets include catalytic processes for remediation of environmentally relevant gases, and novel enzymatic tools for processing nanomaterials.
Michigan/UCSD Autonomic Sensors Team: AFOSR Sponsored Program
Collaboration: Mayer(PI), Shtein, Sept (U. of Michigan), and Yang (UCSD)
Disposable, energy-converting, high stability, ion channel sensor materials. This multi-university research team seeks novel, cascade sensors based on chemical receptors and new synthetic approaches to highly stable, but responsive compartmentalized reactions. We take biological cascades and sequential, parallel reactions prevalent in nature as inspiration in the design of a new class of autonomous sensors and devices.
Autonomous Reactive Chemical Systems
This project involves the development of chemical systems capable of selectively sensing small molecule and biomolecular stimuli, and then responding through changes in materials properties over multiple length scales. This is a significant challenge in chemistry, and relies not just on selective recognition, but on propagation of a response. Chemical feedback loops, both positive and negative, are a major area of interest here, as are templating and replicative mechanisms of action in pursuit of our goals.
This program has several sub-aims including 1) Stabilization of biomolecules in non-natural and harsh environments such that they can be deployed in the real world as components in sense-and-response systems. 2) Reactive, informational systems for signal propagation over multiple length scales.
Materials for Biomedicine
Collaboration: Hall, Mattrev, Hahn (Radiology, UCSD)
This program has as its chief aim the development of a new approach to drug and diagnostic delivery, namely the Enzyme-Directed Assembly of Particle Theranostics. This approach relies on tumor-associated enzymes and factors to accumulate and collect synthetic materials for building healing and labeling scaffolds to self-assemble in diseased tissue. We have successfully demonstrated that this is a viable approach to nanomaterial targeting in vivo, and seek to determine if the approach is general in the context of multiple disease types and imagine modalities. One key part of this program is the development and implementation of multiple imaging tools for characterizing targeted materials in vivo and in ex vivo analysis. We contend that the continued, aggressive development of novel techniques is an absolutely critical part of any strategy seeking to utilize complex, injectable nanoscale particles.
Smart, Programmable Drug Delivery Systems
Programmable pharmacokinetics for advanced nanocarriers as diagnostic and drug delivery tools. Shape, elastic modulus and surface chemistry all play important roles in controlling biodistribution, toxicity, clearance and accumulation of materials when injected into living organisms. This program has many broad goals pertaining to the development of switchable, injectable materials for studying and utilizing these effects for new ways of regulating and switching injected materials by remote control. This represents a new approach to personalized medicine and programmed real-time control over imaging with implications in diagnosis and treatment of disease.
Collaboration: Christman (UCSD Bioengineering)
Autonomously assembling nanomaterial scaffolds for treatment of myocardial infarction. This involves the remote control assembly of healing scaffolds within damaged tissue, guided by signals associated with that tissue. The possibility for transforming how materials are used to control tissue repair is being explored in this multi-lab, multidisciplinary effort uniting advanced nanomaterials and tissue engineering.
2012 NIH Director's Transformative Research Award National Heart, Lung and Blood Institute