Design strategies for programmable oligonucleotide nanotherapeutics

Abstract

A systematic review on how to design different programmable nanotherapeutics using oligonucleotides as building blocks or as surface and matrix modifiers for controlled and targeted delivery of various therapeutic agents in presented.

Figure 1.

Schematic representations of (a) DNA-brick self-assembly nanostructures designed as gene and drug delivery devices, (b) a 2D tile (an origami blueprint) formed by 27 short strand staple DNAs using the open source (MIT license) Cadnano 2 software and a 3D rectangular DNA origami obtained by hybridization of an M13mp18 DNA scaffold with the 27 short strand staple DNAs and (c) selected DNA origamis (red: scaffold DNA; green: staple DNAs) investigated as gene and drug delivery devices.

Figure 1.

Schematic representations of (a) DNA-brick self-assembly nanostructures designed as gene and drug delivery devices, (b) a 2D tile (an origami blueprint) formed by 27 short strand staple DNAs using the open source (MIT license) Cadnano 2 software and a 3D rectangular DNA origami obtained by hybridization of an M13mp18 DNA scaffold with the 27 short strand staple DNAs and (c) selected DNA origamis (red: scaffold DNA; green: staple DNAs) investigated as gene and drug delivery devices.

Figure 2.

Schematic representation of CpG-ODN-modified tube-shaped DNA origami. Conjugation of nonmodified and partially or fully phosphorothioate (PTO)-modified phosphate backbone CpG-ODN to tube-shaped DNA origami and tcellular uptake with subsequent cytokine and surface molecules production. 1. Endocytotic internalization of the DNA origami; 2. vesicle segregation by the Golgi apparatus containing the transmembrane Toll-like receptor 9 (TLR9); 3. fusion of endosomes with the DNA origami and TLR9 containing vesicle; 4. recognition of CpG-ODN sequence by TLR9 and starting of signaling cascade; 5. expression of surface molecules and release of cytokines that stimulate immune response. Figure reproduced, with permission, from [76].

Figure 3.

Self-assembly of DNA–lipid conjugates into big spherical unilamellar vesicles that undergo phase transition into smaller spherical micelles in a fully reversible fashion via DNA hybridization (+ DNA₂) and strand invasion (+ DNA₃) cycles. Figure reproduced, with permission, from [52].

Figure 4.

Schematic representation of various hybrid nanoparticles prepared by surface modification of different nanotherapeutics using oligonucleotides ( = DNA, = aptamer).

Figure 5.

Schematic illustration of functionalization of gold nanorods with DNA origami clamps. (a) The gold nanorods were first modified with thiolated ssDNA. The ssDNA-gold nanorod was then encapsulated by the DNA clamp through DNA hybridization with the capture and complementary strands inside the clamp. (b) Further strands outside the clamp formed specific recognition sites for other gold nanoparticles that were modified with complementary ssDNA. Figure reproduced, with permission, from [77].

Figure 6.

Schematic representation of the use of DNA crosslinkers in the preparation of nanogels or polymeric nanoparticles that respond to a specific strand displacement DNA. (a) The primary and complementary DNAs are attached to the monomer before polymerization. (b) Prepolymers are chemically crosslinked with the primary DNA and crosslinking was carried out using a two-arm complementary DNA.

Figure 7.

Ten kDa FITC-dextran (green) was encapsulated in two semi-DNA icosahedrons (black) held together by ten aptamers (red) to form a complete DNA icosahedron. In the presence of the molecular trigger cdGMP (gray hexagons), the aptamers folded back leading to opening of the DNA icosahedron and simultaneous release of the encapsulated dextran. Figure reproduced, with permission, from [98].