Size controllable DNA nanogels from the self-assembly of DNA nanostructures through multivalent host–guest interactions

Abstract

Nanogels made of biomolecules are one of the potential candidates as a nanocarrier for drug delivery applications. The unique structural characteristics and excellent biocompatibility of DNA suggest that DNA nanogels would be an ideal candidate. Herein, a general design strategy for the crafting of DNA nanogels with controllable size using the multivalent host-guest interaction between β-CD functionalized branched DNA nanostructures as the host and a star-shaped adamantyl-terminated 8-arm poly(ethylene glycol) polymer as the guest is reported. Our results reveal that multivalent host-guest interactions are necessary for the nanogel formation. Nanogels exhibit excellent biocompatibility, good cell permeability and high drug encapsulation ability, which are promising features for their application as a drug carrier. The encapsulation of doxorubicin, an anticancer drug, inside the hydrophobic network of the nanogel and its delivery into cancer cells are also reported. We hope that the general design strategy demonstrated for the creation of DNA nanogels may encourage other researchers to use this approach for the design of DNA nanogels of other DNA nanostructures, and explore the potential of DNA nanogels in drug delivery applications.

Micro and Nanogels for Biomedical Applications

“…Self-assembled nanogels were firstly introduced by Akiyoshi and colleagues, where hydrophilic pullulan polysaccharides were conjugated with hydrophobic cholesterol units and sonication of these amphiphilic polysaccharide derivatives in water yielded intramolecularly self-aggregated monodisperse particles with 25±5 nm sizes [22]. Moreover numerous microgels and nanogels have been reported by self-assembly process including synthetic and natural polymeric substrates such as poly(Nisopropylacrylamide) (PNIPAM) [23], poly(hydroxyethyl methacrylate) (p(HEMA)) [24], polysaccharides [25], pullulan [26], chitosan (CHI) [27][28][29][30][31][32], alginic acid [24], dextran [33,34], hyaluronic acid (HA) [35][36][37][38][39], starch derivatives [40], and polyphenols [41][42][43][44], proteins [45], polypeptides [46,47], various amino acids [48], and DNA [30,49,50] all of which were intended for biomedical applications in delivery of various therapeutic agents including small molecules, proteins, drugs, and genes and siRNAs.…”

NanoTRAIL‐Oncology: A Strategic Approach in Cancer Research and Therapy

“…Due to its unique biological structure, some short DNA can recognize the biomarkers expressed on tumor cells, which could be exploited as a targeted delivery platform . DNA carrier also has great potential to deliver cytokines because of its special characteristics, such as responsiveness to the tumor microenvironment, unique structure, and excellent biocompatibility . Transformable DNA has been designed as an emerging nanocarrier to target the plasma membrane ( Figure ).…”

Dictating Nanoparticle Assembly via Systems-Level Control of Molecular Multivalency

“…[2][3][4][5] However, while the manipulation of molecular bonding has been shown to be a powerful means to control the thermodynamics of nanoscale assembly, it is also true that the nanoscale arrangement of these molecular binding groups can affect the overall strength of the bonds being formed. [6][7][8][9] In other words, not only can changes to molecular geometry alter material ordering at larger length scales, but changes to these larger scale structures can also cause alterations to molecular behavior. Indeed, manipulating the relative positions of individual chemical moieties is a common design principle used in nature to control the strength and specificity of multivalent intermolecular interactions including avidity in antibody-antigen binding, 10 substrate selectivity at the active site of catalytic enzymes, 11 and strong yet dynamic carbohydrate-regulated cell adhesion.…”