ABSTRACT
The DNA origami technique allows the precise synthesis of complex, biocompatible nanomaterials containing small molecules, biomolecules, and inorganic nanoparticles. The negatively charged phosphates in the backbone make DNA highly water-soluble and require salts to shield its electrostatic repulsion. DNA origamis are therefore not soluble in most organic solvents. While this is not problematic for applications in biochemistry, biophysics, or nanomedicine, other potential applications, processes, and substrates are incompatible with saline solutions, which include the synthesis of many nanomaterials, and reactions in templated synthesis, the operation of nanoelectronic devices, or semiconductor fabrication. To overcome this limitation, we coated DNA origami with amphiphilic poly(ethylene glycol) polylysine block copolymers and transferred them into various organic solvents including chloroform, dichloromethane, acetone, or 1-propanol. Our approach maintains the shape of the nanostructures and protects functional elements bound to the structure, such as fluorophores, gold nanoparticles, or proteins. The DNA origami polyplex micellization (DOPM) strategy hence enables solubilization or a phase transfer of complex structures into various organic solvents, which significantly expands the use of DNA origami for a range of potential applications and technical processes.
Subject(s)
Metal Nanoparticles , Nanostructures , 1-Propanol , Acetone , Chloroform , DNA/chemistry , Gold , Methylene Chloride , Nanostructures/chemistry , Phosphates , Polyethylene Glycols/chemistry , Polylysine , Polymers/chemistry , Salts , Solubility , Solvents , Water/chemistryABSTRACT
The formation of beta-amyloid (Aß) plaques is a classical hallmark of Alzheimer's disease (AD) that is associated with the promotion of neuroinflammation and subsequent neurotoxicity. Given the limited therapeutic options for targeting and clearing Aß plaques in AD, there is an urgent need to develop effective approaches to reduce plaque accumulation. The objective of this study was to validate mild magnetic nanoparticle (MNP) hyperthermia technology as a strategy to clear Aß deposits and determine the impact on microglia functionality. Our results demonstrated that the heating of MNPs localized to Aß aggregates upon exposure to high frequency alternating magnetic field (AMF) was sufficient to disrupt Aß plaques, resulting in its fragmentation. Importantly, this could facilitate the phagocytic clearance of Aß as well as attenuate pro-inflammatory responses by human microglial cells. Our results support the feasibility of mild MNP/AMF hyperthermia as a new strategy for reducing beta-amyloid burdens in Alzheimer's disease.
