Controlling DNA–nanoparticle serum interactions

Abstract

Understanding the interaction of molecularly assembled nanoparticles with physiological fluids is critical to their use for in vivo delivery of drugs and contrast agents. Here, we systematically investigated the factors and mechanisms that govern the degradation of DNA on the nanoparticle surface in serum. We discovered that a higher DNA density, shorter oligonucleotides, and thicker PEG layer increased protection of DNA against serum degradation. Oligonucleotides on the surface of nanoparticles were highly resistant to DNase I endonucleases, and degradation was carried out exclusively by protein-mediated exonuclease cleavage and full-strand desorption. These results enabled the programming of the degradation rates of the DNA-assembled nanoparticle system from 0.1 to 0.7 h −1 and the engineering of superstructures that can release two different preloaded dye molecules with distinct kinetics and half-lives ranging from 3.3 to 9.8 h. This study provides a general framework for investigating the serum stability of DNA-containing nanostructures. The results advance our understanding of engineering principles for designing nanoparticle assemblies with controlled in vivo behavior and present a strategy for storage and multistage release of drugs and contrast agents that can facilitate the diagnosis and treatment of cancer and other diseases.nanoparticle assembly | DNA nanostructures | serum stability | serum resistance | controlled cargo release

Systemic delivery of the tumor necrosis factor gene to tumors by a novel dual DNA-nanocomplex in a nanoparticle system

“…One of the major challenges has been the systemic delivery of cationic peptide-DNA complexes to tumor cells at sufficient levels because of DNA degradation in serum (17, 21). To address this obstacle, we developed novel polymeric NPs with high molecular weight PLA for the systemic delivery of peptide cargoes to tumor cells (18, 20).…”

“…A histidine and cysteine modified arginine (HCR) peptide component of the NC has been designed for maintaining the balance of DNA condensation and intracellular release and nuclear localization (16). For delivery in vivo , the NC has been surrounded by a polymer diblock NP to circumvent the challenge of DNA-nanoparticle serum interactions that have limited the field (17). Our results demonstrate that this approach is highly effective in conferring TNF-induced anti-tumor activity in the absence of toxicity.…”

Programmable and Multifunctional DNA‐Based Materials for Biomedical Applications

“…Such a system realized multistage cargo release with programmable degradation rates, because outer‐layer structures prevented the serum factors responsible for assembly degradation from reaching the inner layer. In addition, the higher the DNA density, the shorter the oligonucleotides, and the thicker the PEG layer on AuNPs, the better the protection of DNA against serum degradation . Through loading fluorescent dyes on DNA linker in this study, it is optimistic that such a system can be transformed to multitherapeutic delivery usages.…”

“…Since the distance between core and satellite AuNP is adjustable by adding molecular stimuli (simple DNA strands), two‐layered AuNP–DNA superstructures with two types of same “core” loaded cargos were made . Such a system realized multistage cargo release with programmable degradation rates, because outer‐layer structures prevented the serum factors responsible for assembly degradation from reaching the inner layer.…”

“…DNA structure was at first suggested by James Watson and Francis Crick as what is now accepted as the double‐helix model more than six decades ago. In the 1980s, Seeman's pioneering work in the area of DNA nanotechnology assigned DNA as biomaterial usage. Since then, high self‐recognition and programmability of DNA molecules were heavily investigated by creating considerable DNA nanostructures with predesigned arrangement and DNA nanomachines with customized functionality.…”