Smart DNA Vectors Based on Cyclodextrin Polymers: Compaction and Endosomal Release

Abstract

We successfully designed fine-tuned DNA vectors based on cyclodextrin polymers combined with two new adamantyl derivatives, leading to significant transfection associated with low toxicity.

Cyclodextrin-Mediated Hierarchical Self-Assembly and Its Potential in Drug Delivery Applications

“…[60][61][62] Inclusion complexation between initially neutral pbCD and a series of amphiphilic cationic connectors, consisting of adamantane group, spacers with different chemical nature and length, and a mono-or bicationic polar head, resulted in the formation of reversible pseudopolycation. The latter proved to hierarchically self-assemble with DNA to yield polyCDplexes (Fig.…”

“…4b). 62 The latter, although being unable to compact DNA itself, when used in combination with cationic Ada5, proved to act as an efficient endosomal escape enhancer due to its "proton sponge" properties. 63 Threading of CDs along the hydrophobic polymer chains or blocks, dubbed as "rotaxanation," is widely known to endow the resulting supramolecular rotaxanes with higher hydrophilicity, flexibility, and bioavailability.…”

“…The first image (X ¼ 0) represents free pDNA in water. Adapted from Wintgens et al62 containing gene vector via inclusion complexation prior to polyplex formation. Once inside the cell, the protective guest polymer corona is removed by S-S bond reduction and the genetic material is released.…”

A Versatile Approach towards the Compaction, Decompaction, and Immobilization of DNA at Interfaces by Using Cyclodextrins

“…A recent review by Gonzalez-Perez and Dias [9] summarized the current methods for controlling the conformation of DNA, in particular through decompaction processes under different conditions. [11] We investigate the temperature dependence of interactions of b-cyclodextrin (CD)/hexadecyltrimethylammonium bromide (CTAB) self-assemblies with DNA during the decompaction of DNA/CTAB complexes. A similar conclusion has recently been reached by Grueso et al, based on a multifaceted study on the interactions of cationic surfactant hexadecyltrimethylammonium bromide (CTAB) with calf thymus DNA.…”

“…These systems are very promising, owing to their modularity and low cell toxicity; however, some of their properties, such as sensitivity towards serum, have not yet been optimized. [11] We investigate the temperature dependence of interactions of b-cyclodextrin (CD)/hexadecyltrimethylammonium bromide (CTAB) self-assemblies with DNA during the decompaction of DNA/CTAB complexes. By combining direct imaging techniques with density and sound-velocity measurements, we can explain the decompaction process and suggest a suitable model.…”