Nanomanufacturing with DNA Origami: Factors Affecting the Kinetics and Yield of Quantum Dot Binding

Abstract

Molecularly directed self-assembly has the potential to become a nanomanufacturing technology if the critical factors governing the kinetics and yield of defect-free self-assembled structures can be understood and controlled. The kinetics of streptavidin-functionalized quantum dots binding to biontinylated DNA origami are quantitatively evaluated and to what extent the reaction rate and binding efficiency are controlled by the valency of the binding location, the biotin linker length, and the organization, and spacing of the binding locations on the DNA is shown. Yield improvement is systematically determined as a function of the valency of the binding locations and as a function of the quantum dot spacing. In addition, the kinetic studies show that the binding rate increases with increasing linker length, but that the yield saturates at the same level for long incubation times. The forward and backward reaction rate coefficients are determined using a nonlinear least squares fit to the measured binding kinetics, providing considerable physical insight into the factors governing this type of self-assembly process. It is found that the value of the dissociation constant, K d , for the DNA-nanoparticle complex considered here is up to seven orders of magnitude larger than that of the native biotinstreptavidin complex. This difference is attributed to the combined effect that the much larger size of the DNA origami and the quantum dot have on the translational and rotational diffusion constants.

High precision and high yield fabrication of dense nanoparticle arrays onto DNA origami at statistically independent binding sites

“…The average probability of AuNP site-occupation was 0.99 ± 0.06 for H1, 0.98 ± 0.03 for H2, 0.98 ± 0.04 for H3 – which are comparable with the 4× AuNP arrays shown in Figure 3. In comparison, the average probability of QD site-occupation was 0.79 ± 0.41 for H1, 0.84 ± 0.37 for H2, 0.79 ± 0.26 for H3 – which agree with previous studies, 32,33 and suggests that the 2× biotin binding sites for QDs are equivalent to the 2× DNA binding sites for AuNPs.…”

“…Binomial distributions are included for simple comparison with the literature as a model to validate the independence of the binding sites without free parameters in the equation. 32,33 Trinomial distributions are included to analyze more complex cases where the number of bound AuNPs exceeded the number of binding sites.…”

“…47 In comparison, Ko et al demonstrated an increased attachment probability of QDs onto DNA origami using trivalent biotin binding sites. 32 Within their study, the yield of streptavidin-functionalized QDs binding to biotinylated DNA origami was controlled by the: biotin linker length, valency (i.e. # of tethers) of the binding location, organization of the binding locations, and spacing of the binding locations.…”

A multifunctional DNA origami as carrier of metal complexes to achieve enhanced tumoral delivery and nullified systemic toxicity

“…Researchers have developed the technique of tile and origami-based DNA hybridization to fabricate nanoscale projects with desired size and shapes, such as capital letters [10], dolphin [11], Chinese characters and 3 dimensional (3D) shapes including crystal lattices [12], spheres and screws [13]. With the development of DNA technology, DNA origami is considered as prospective candidate for drug delivery because it has unique advantages including (1) predictable and well-defined structure [14], (2) high efficacy of drug loading [15], (3) chemically modifiable for drug design [16], (4) stability in physiological M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 5 conditions [17] and (5) superior biocompatibility [18]. Högberg et al, fabricated DNA nanotubes to enhance the release rate and anti-proliferative effect of DOX in cancer cells [19].…”

DNA Directed Self‐Assembly of Fluorescent Colloidal Semiconductor Quantum Dots and Plasmonic Metal Nanoparticles Heterogeneous Nanomaterials

“…[28,29] Since the invention of the DNA origami technique, the field of convergence of CQDs or/and NPs on DNA scaffolds has undergone tremendous development. [7,[30][31][32][33] Compared to, as described in the former part, self-assembly of ssDNA functionalized CQDs and MNPs, convergence of CQDs and NPs on DNA scaffolds strengths the mechanical rigidity of the hybrid nanosystem, and allows easily managing the ratio between nanoparticles and increasing heterogeneity.…”