Double-degradable responsive self-assembled multivalent arrays – temporary nanoscale recognition between dendrons and DNA

Abstract

Article:Barnard, A., Posocco, P., Fermeglia, M. et This article reports self-assembling dendrons which bind DNA in a multivalent manner. The molecular design directly impacts on self-assembly which subsequently controls the way these multivalent nanostructures bind DNA -this can be simulated by multiscale modelling. Incorporation of an S-S linkage between the multivalent hydrophilic dendron and the hydrophobic units responsible for self-10 assembly allows these structures to undergo triggered reductive cleavage, with dithiothreitol (DTT) inducing controlled breakdown, enabling the release of bound DNA. As such, the high-affinity selfassembled multivalent binding is temporary. Furthermore, because the multivalent dendrons are constructed from esters, a second slow degradation step causes further breakdown of these structures. This two-step double-degradation mechanism converts a large self-assembling unit with high affinity for 15 DNA into small units with no measurable binding affinity -demonstrating the advantage of selfassembled multivalency (SAMul) in achieving highly responsive nanoscale binding of biological targets.

Anticancer drug nanomicelles formed by self-assembling amphiphilic dendrimer to combat cancer drug resistance

“…S2A. Insights into the structural properties of these micelles were further gained by performing mesoscale computational studies using dissipative particle dynamics (DPD) (22), a well-established technique in soft matter simulations to study amphiphilic systems at the nanoscale (23)(24)(25). These simulations highlighted the hydrophobic nature of the micellar core (Fig.…”

From fundamental supramolecular chemistry to self-assembled nanomaterials and medicines and back again – how Sam inspired SAMul

“…6). 40 This allows these structures to undergo triggered reductive cleavage, with dithiothreitol (DTT) inducing controlled breakdown, enabling the release of bound DNA -another example of temporary 'on-off' multivalency. Furthermore, because the multivalent dendrons are constructed from esters, a second slow degradation step takes place converting the dendron into very small molecular-scale building blocks, clearly illustrating the potential of such self-assembled systems including multiple degradable units.…”

Biodegradable PEG–dendritic block copolymers: synthesis and biofunctionality assessment as vectors of siRNA

“…27 In the area of NA delivery these are restricted to very few examples with amineterminated bis-HMPA [2,2-bis(hydroxymethyl)propanoic acid] dendrons for the encapsulation of DNA, largely described by Smith and coworkers. [37][38][39][40][41] The challenge associated to combine in the same structure unprotected primary/secondary amine groups -needed to get the cationic charge to complex NAs -with hydrolyzable (and so, electrophilic) bonds adds extra struggle to the already difficult task of engineering biodegradable dendritic vectors.…”