Responsive soft materials made by supramolecular self-assembly
Self-assembly is emerging as a superior method to prepare adaptive and responsive nanomaterials. The structure and function of these materials is entirely determined by the dynamic and weak interactions of the constituent molecular â€œbuilding blocksâ€Â of the material. Since the inherent interactions are weak, these versatile materials readily respond to even small changes and stimuli in their environment. Moreover, these materials are biomimetic and contain large amounts of water, so that application in biomedical technology can be foreseen.
This lecture will highlight self-assembled nanocontainers based on cyclodextrins that respond to various external stimuli. Amphiphilic cyclodextrins form bilayer vesicles in aqueous solution and the surface of these vesicles can be functionalized using hostguest chemistry. Shear-thinning hydrogels result if the cyclodextrin vesicles are mixed with adamantane-functionalized polymers, which act as supramolecular cross-linkers. Photo-triggered payload release from supramolecular hydrogels is enabled by incorporation of azo-modifed peptides. Polymer-shelled vesicles and polymer nanocontainers are obtained if the cyclodextrin vesicles are decorated with adamantaneterminated poly(acrylic acid), which can be cross-linked with diamines. Recently, we have also shown that this polymer shell is redox-responsive if the cross-linker contains a disulfide unit. The resulting nanocontainer can deliver cargo into cells.
Furthermore, the lecture will include several examples of the transfer of the concept of stimulus-responsive assembly to nanoparticles and nanofilms.
How RNase HI (E. coli) can be dictated to the site-selective hydrolysis of mRNA in the antisense/mRNA duplex?
A detailed kinetic study of 36 single modified AON (antisense)-RNA heteroduplexes shows site-dependent modulation of RNase H promoted cleavage of the complementary mRNA strand, which We have steered to take place at the purine (Pu)-pyrimidine (Py) junctions by over 90% of the total RNA cleavage products.This is a result of engineering a weaker Pu-Py stacking in the RNA strand of the duplex. A plausible mechanism of this RNase H mediated cleavage of the mRNA involves the enhancement of the total rate by up to 25%, compared to that of the native AON. Such a scenerio has been engineered by us by introducing a single modification in the modified AON strand. This strategy takes advantage of factors as diverse as, 1. Enhanced nucleolytic stability of the AON strand, 2. The amount RNase H required in the diseased cell to cleave the complementary mRNA strand is minimal because of, by far a major, single cleavage site, 3. The amounts of administerd AON required to cleave the mRNA strand in the hybrid is much less than equimolar ratio, thereby reducing the non-specific mRNA binding to in a chemotherapeutic strategy, and overall reduction of the toxic side effects.