Advances in intracellular delivery through supramolecular self-assembly of oligonucleotides and peptides

Abstract

Cells utilize natural supramolecular assemblies to maintain homeostasis and biological functions. Naturally inspired modular assembly of biomaterials are now being exploited for understanding or manipulating cell biology for treatment, diagnosis, and detection of diseases. Supramolecular biomaterials, in particular peptides and oligonucleotides, can be precisely tuned to have diverse structural, mechanical, physicochemical and biological properties. These merits of oligonucleotides and peptides as building blocks have given rise to the evolution of numerous nucleic acid- and peptide-based self-assembling nanomaterials for various medical applications, including drug delivery, tissue engineering, regenerative medicine, and immunotherapy. In this review, we provide an extensive overview of the intracellular delivery approaches using supramolecular self-assembly of DNA, RNA, and peptides. Furthermore, we discuss the current challenges related to subcellular delivery and provide future perspectives of the application of supramolecular biomaterials for intracellular delivery in theranostics.

Polyamine‐Functionalized 2′‐Amino‐LNA in Oligonucleotides: Facile Synthesis of New Monomers and High‐Affinity Binding towards ssDNA and dsDNA

“…[3,14,15] Different strategies have been proposed to improve the intracellular delivery of ONs. [16][17][18][19][20][21][22][23] Amongt hem, bioconjugationof polyamines and cationic cell-penetrating peptides to ONs are notable examples that affect the overall charge state of the resulting ONs. [15,[24][25][26] The issue of nuclease stabilityc an at least in part be tackledb yi ntroducing chemicalm odifications or replacing the naturalr ibose-phosphate backbone with artificial analogues.…”

Self-assembled mRNA vaccines

“…Endocytosis is initiated by dynamic non-covalent interactions between the plasma membrane and the nanocarrier in proximity to the cells. It is known that the physicochemical properties of nanocarriers, such as size, shape, surface charge, and surface composition, affect the defined pathways of endocytosis - macropinocytosis, caveolin-mediated, clathrin-mediated, clathrin, and caveolin-independent [ 122 , 123 ]. After endocytosis, internalized nanocarriers are transported to the early endosomes, followed by maturation to multi-vesicular late endosomes.…”

Nanoscale Self-Assembly for Therapeutic Delivery

“…The basic principle behind DNA nanotechnology is the complementary base pairing. Using this principle, a large number of simple DNA nanostructures have been produced (Hu et al, 2018;Madhanagopal et al, 2018;Kim et al, 2019). Initially, the research on DNA nanotechnology was initiated with the formation of simple topological morphologies which later on advanced to production of DNA tiles, periodic lattices, and 2D and 3D structures.…”