DNA as a Nanomaterial Towards Directed Self-assembly of Novel Nano-Architecture
Over the past two decades, DNA has emerged as a promising building block for the programmed and directed assembly of nanoscale components into complex, dynamic, and highly functional structures. Our group is interested in exploring the interaction between DNA and common nanoscale components and translates our knowledge into exciting new applications in sensing, synthesis, patterning, and advancing basic science. Our major research focus includes:
DNA Mediated Assembly and Growth of Nanoparticles
We have explored the interaction of different DNA molecules on the morphology of gold nanoparticles during synthesis (1). While spherical nanoparticles (AuNS) are observed in the presence of 30-mer poly T, like that in the absence of DNA, 30-mer poly A or poly C induces formation of the flower-shaped gold nanoparticle (AuNF). Furthermore, DNA functionalization with high stability was realized in situ during the one-step synthesis while retaining their biorecognition ability, allowing programmable assembly of new nanostructures.We have also shown that the DNA-functionalized nanoflowers can be readily uptaken by cells and visualized under dark-field microscopy. We have also taken advantage of using DNAzymes and aptamers to direct the assembly of gold nanoparticles.
This has led to genetic control of both nanoparticle assembly and disassembly in response to chemical stimuli with controlled cooperativity (2-9). Such a concept has been extended to controlled assembly of other materials such as nanotubes (10 ) and quantum dots ( 11). Furthermore, a major problem encountered by the assembly method is the presence of imperfect structures or errors. Most researchers focus on optimizing the assembly process to minimize errors. Proof-reading and error correction ubiquitously exist in biology. We have demonstrated proof-reading and error correction in nanomaterials assembly (12). The work represents a potential paradigm shift in nanoscale science and engineering. Current work includes the above mentioned as well as fundamental studies of interaction between specific DNA bases with different surfaces and its influence on nanoparticle growth, asymmetric assembly of gold nanoparticles heterogeneous structures, as well as synthesis and characterization of novel structures for optical, electronic, and sensing applications.
Directed Nanoscale Self-Assembly on DNA Scaffold
DNA is ideally suited as a scaffolding building block due to its well understood and predictable structure, stiff backbone, and easy chemical modification. While end modification of DNA is well reported, there are considerably less reported techniques for intra-strand modification of DNA. We have demonstrated a simple intra-strand modification through the introduction of a phosphorothioate modification on the backbone of the DNA. Through rational design of short bifunctional linkers, it is possible to demonstrate nanoscale control and alignment of gold nanoparticles (13) and different proteins (14) onto the backbone of a double-strand DNA. This technique offers great versatility for more complex DNA scaffolds due to its minimal effect on hybridization. We are currently exploring the functionalization of 2D and 3D DNA scaffolds using phosphorothioate modification as well as exploring additional chemistries for DNA functionalization.
Reversible Cell-Specific Drug Delivery with Aptamer-Functionalized Liposomes
Nucleic acid based aptamers provide excellent alternatives to antibodies as cell-specific agents and therefore are promising targeting ligands for targeted drug-delivery systems. One the other hand, Liposomes are by far the most successful drug-delivery systems and a number of liposome-based systems have been approved by the US Food and Drug Administration for disease treatment in the clinic. Here we want to take advanges of both system and designed the controlled formulation of aptamer-conjugated, anticancer drug-encapsulating multifunctional liposomes (15). Cancer-cell-specific targeting and drug delivery are demonstrated by using this delivery platform. Furthermore, we also show for the first time that a complementary DNA (cDNA) of the aptamer can function as an antidote to disrupt aptamer-mediated targeted drug delivery. This strategy for reversible delivery can, in principle, be adapted to a broad range of chemotherapy agents.
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