Liposomal Spherical Nucleic Acid Scaffolded Site-Selective Hybridization of Nanoparticles for Visual Detection of MicroRNAs

Abstract

In this study, the advanced liposomal spherical nucleic acid (L-SNA) is exploited for the first time to establish a spherical, three-dimensional biosensing platform by hybridizing with a set of nanoparticles. By hydrophilic and hydrophobic interactions as well as programmable base-pairing, red-emission quantum dots (QDs), green-emission QDs, and gold nanoparticles (AuNPs) are encapsulated into the internal aqueous core, the intermediate lipid bilayer, and the outer SNA shell, respectively, producing an L-SNA–nanoparticle hybrid. As a result of the site-selective encapsulation, the hybrid constitutes a liposomal fluorescent “core–resonance energy transfer” system surrounded by a SNA shell, as is imaged at the single-particle resolution by confocal microscopy. With the outer SNA shell as three-dimensional substrate for duplex-specific nuclease target recycling reaction, the hybrid is capable of amplified detection of microRNAs, featuring one target to many AuNP-manipulated, dual-emission QD-based ratiometric fluorescence. More importantly, the ratiometric fluorescence facilitates the hybrid to visualize microRNAs with remarkably high resolution, which is exemplified by traffic light-type transition in fluorescence color for diagnosing circulating microRNAs in clinical serum samples. Substantially, the controllable hybridization with functional nanoparticles opens an avenue for the exciting biomedical applications of liposomal spherical nucleic acids.

Cerasome Spherical Nucleic Acid Nanostructure-Based AND Logic Gate-Guided Dual-DNAzyme Walker for Accurate Cancer Cell Identification

“…44 Cerasome-forming lipid (CFL), N-[N-(3-triethoxysilyl)propylsuccinamoyl] dihexadecylamine, was synthesized according to the reported method. 45 QD2@C was prepared by a modified thin film-hydration method, 46 with CFL, DPPC, and DSPE-PEG2000-COOH (with a molar ratio of 2:2:1) as the lipids. By the method, a coarse QD2@C suspension that includes large vesicles of QD2@C, small vesicles of QD2@C, free QDs, and cerasome cores without QD was obtained.…”

Spherical nucleic acids: Organized nucleotide aggregates as versatile nanomedicine

“…[ 158 ] Within the LSNA, hydrophilic QDs, hydrophobic QDs, and AuNPs are able to mix in a site-selective manner, constituting a liposomal “core-resonance energy transfer” system surrounded by an SNA shell ( Figure 3C ), for colorimetric amplified detection of miRNAs through an auxiliary biochemical reaction. [ 49 ] Li et al established an electrochemiluminescence sensing platform for circulating miRNAs using AuNPs@G-quadruplex SNA enzyme (SNAzyme) as a nanocatalyst, with a portable smartphone as a detector to visualize AMI-associated miRNAs in actual patient serum for the first time. [ 160 – 162 ] Wei et al, developed an enzyme-free SPR imaging based on a catalytic hairpin device and SNA to enable differentiation of single-base differences and members of homologous miRNA families.…”

“…Reproduced with permission: Copyright 2020, American Chemical Society. [ 49 ] (D) A Pro-SNA with functional protein as the core. Reproduced with permission: Copyright 2015, American Chemical Society.…”