Cellular uptake of covalent and non-covalent DNA nanostructures with different sizes and geometries

Abstract

DNA nanostructures of different sizes and forms are internalized in cells through the LOX-1 receptor with different intracellular fate and lifetime.

In Silico and In Cell Analysis of Openable DNA Nanocages for miRNA Silencing

“…It provides a safe hydrophilic environment for trapping useful payloads, and DNA motifs can be engineered to control size, shape, and switchable open/close mechanisms [2]. DNA strands can be modified with cellular recognition signals, such as folate, transferrin, or aptamers, which permit the assembly of functionalized DNA-based nanostructures (DNS) useful for selective targeting into cells through receptor-mediated mechanism [3][4][5]. Due to their intrinsic biocompatible, nontoxic, and stable properties, DNS have been extensively investigated for various biomedical applications, such as drug delivery, cellular biosensing, and in vivo imaging [4][5][6][7][8], and, more recently, in gene silencing and RNA anticancer therapy [9,10].…”

“…DNA nanostructures have also been functionalized to selectively interact with intracellular miRNA, mainly to detect their concentration, using electrochemical current or fluorescence signals [15][16][17]. Here, taking advantage of our experience matured in the last years in the characterization of different types of fully covalently octahedral DNA nanocages [11,12,[18][19][20][21], including their receptor-mediated cell targeting and their efficacy in selective drug delivery [5,22,23], we propose a new nanostructure for a possible therapeutic use as an efficient captor of the oncogenic miR21. For this purpose, we have initially engineered in one face of a truncated DNA cage four DNA hairpins complementary to a specific oligonucleotide (Fuel), to form a nanocage (H4-NC) with selective oligonucleotide sequestering activity.…”

Advances in DNA Origami–Cell Interfaces

“…Although the studies mentioned so far have focused primarily on uptake, it is also important for the DNA nanostructure, having entered the cell, to maintain its structure, as far as possible, because this is often also intimately tied to its function inside the cell. Raniolo and co‐workers made DNA nanostructures with different sizes and shapes (Figure A) that were assembled through either covalent or noncovalent bonds . These included TD and OD nanocages (covalent and noncovalent versions), rod‐shaped CM, SBO, and RO DNA origami structures (only noncovalent), which were compared with respect to their stability in serum, cell‐surface binding, internalisation efficiency and intracellular degradation.…”

“…Raniolo and co-workers made DNA nanostructures with different sizes and shapes ( Figure 2A)t hat were assembled through either covalent or noncovalent bonds. [16] These included TD and OD nanocages (covalent and noncovalent versions), rod-shaped CM, SBO, and RO DNA origami structures (only noncovalent), which were compared with respect to their stability in serum, cell-surface binding, internalisation efficiency and intracellulard egradation. They showed that the scavenger receptor LOX-1 could efficiently bind and internalise variousDNA nanostructures.…”

“…From left to right:T etrahedral (TD) and octahedral(OD) nanocages, rodshaped chainmail (CM),s quare box (SBO) and rectangular (RO) origami. Reproduced with permission from ref [16][19]…”