Self-assembled DNA nanocentipedes as multivalent vehicles for enhanced delivery of CpG oligonucleotides

Abstract

We report self-assembled nanocentipedes as multivalent vehicles for the delivery of immunostimulatory CpG ODNs. The multivalent vehicles could be internalized by RAW264.7 cells and stimulate the secretion of large amounts of cytokines, successively inducing effective apoptosis of cancer cells.

Designing Multivalent Ligands to Control Biological Interactions: From Vaccines and Cellular Effectors to Targeted Drug Delivery

“…Varying the ligand valency revealed that a 200‐mer CpG‐Nce was more efficient at being taken up by RAW264.7 cells compared to the ones with a lower density. Also, an increasing trend in the release of TNF‐α and IL‐6 was observed with increasing valency …”

“…Li et al . investigated the role of the multivalent display of aptamers for targeted drug delivery as it relates to the “nanocentipede” construct, which was described in section 2.2 for its ability to display immunostimulatory CpG ODNs . To functionalize the nanocentipede for targeted delivery, the nanocentipede's “trunk” was assembled using the hybridization chain reaction (HCR) of two biotinylated DNA monomers to which streptavidin‐conjugated ZY1 aptamers targeting SMMC‐7221 cells were attached (Figure A).…”

“…The multimeric dendrimers could be efficiently taken up by macrophage-like RAW264.7c ells and showed greater TNF-a releasecompared to the trimericb uilding block. [35] Li et al [36] employedD NA nanocentipedes( Nces) as multivalent vehicles for the delivery of CpG ODNs. The nanocentipede was self-assembled via ah ybridization chain reaction (HCR).…”

“…Also, an increasing trend in the release of TNF-a and IL-6 was observedw ith increasing valency. [36] Zhang et al [37] employed ad ifferents trategy primarily to avoid complicated DNA nanostructure design and the safety concerns associated with the use of double-stranded DNA (dsDNA), whichm ay induce dsDNAa ntibodies and autoimmune responses. They delivered CpGO DNs as DNA nanoflowers (NFs), which were self-assembled from elongated DNA buildingb locks generatedt hrough rolling circle replication (RCR).…”

Self‐Assembled Supramolecular Nanoparticles for Targeted Delivery and Combination Chemotherapy

“…They can form vesicles, polymericn anoparticles, or DNA nanostructures in aqueous solution at room temperatureu nder gentle conditions via noncovalentm odes, such as hydrophilic interactions, [16][17][18] host-guest interactions, [17,19,20] and nucleic acid hybridization. [4,21,22] Therapeutic agentsa re generally loaded in the carriers by physicale ncapsulation, [23][24][25] electrostatic interactions, [9,26] and host-guesti nteractions. [27][28][29] Nanostructures encapsulated only with drugs do not have targeting ability andb lood circulation ability,w hich usually need to be modified with functional molecules through noncovalent interactions.…”