Bala N. S. Thota

Dendritic core-shell systems as soft drug delivery nanocarriers.

Unimolecular micelles are covalently bound molecular architectures and therefore highly stable which makes them particularly attractive for drug delivery. Accordingly, many reports in the literature emphasize the importance of these molecular architectures for nanomedicine. This conceptual review will present some of the recent advances in the application of these dendritic core-shell systems for drug delivery. Unimolecular micelles based on hyperbranched and dendritic cores will be discussed and sorted by the nature of their core and structure.

Carbon-based cores with polyglycerol shells – the importance of core flexibility for encapsulation of hydrophobic guests

Two core-shell nanoparticles with polyglycerol shells and sp3 carbon cores with different flexibilities (soft dendritic polyethylene and hard nanodiamond) were synthesized, their encapsulation capacities were compared, and their ability to transport into tumor cells was investigated. The nanocarrier with a soft core was superior to the hard one.

Crosslinked Redox-Responsive Micelles Based on Lipoic Acid-Derived Amphiphiles for Enhanced siRNA Delivery

Successful application of gene silencing approaches critically depends on systems that are able to safely and efficiently deliver genetic material such as small interfering RNA (siRNA). Due to their beneficial well-defined dendritic nanostructure, self-assembling dendrimers are emerging as promising nanovectors for siRNA delivery. However, these kinds of vectors are plagued with stability issues, especially when considered for in vivo applications. Therefore, in the present study, disulfide-based temporarily fixed micelles are developed that can degrade upon reductive conditions, and thus lead to efficient cargo release. In detail, lipoic acid-derived crosslinked micelles are synthesized based on small polymerizable dendritic amphiphiles. Particularly, one candidate out of this series is able to efficiently release siRNA due to its redox-responsive biodegradable profile when exposed to simulated intracellular environments. As a result, the reduction-triggered disassembly leads to potent gene silencing. In contrast, noncrosslinkable, structurally related constructs fails under the tested assay conditions, thereby confirming the applied rational design approach and demonstrating its large potential for future in vivo applications.

Perfluoroalkylated linear polyglycerols and their supramolecular assemblies in aqueous solution

In this study, amphiphiles composed of linear polyglycerols (LPGs) with hydroxyl, methoxy, and ethoxy side groups and end capped with one or two perfluorooctyl chains (Rf8) have been designed to form supramolecular architectures. The amphiphiles and bolaamphiphiles are capable of self-assembling into spherical and flat micelles as well as nonionic unilamellar vesicles (niosomes) in aqueous solution. The fluorous compartments of the micelles preferentially encapsulate a trifluoromethylated Disperse Red 1 compared to the unaltered dye. Micellar solutions of methoxy LPG compounds show a transition in water at temperatures of 38 °C (2) and 33 °C (5) in which reversibly larger agglomerates are formed. Both amphiphiles also form very stable unilamellar vesicles with diameters ranging from 30 nm up to 10 μm, if prepared via a thin film hydration method, which remain intact above 38 °C.

Dendronylation: Residue-specific chemoselective attachment of oligoglycerol dendrimers on proteins with noncanonical amino acids

Polyglycerol dendrimers as an important class of polymeric materials especially attractive for covalent attachment to therapeutic proteins as a useful alternative to traditional PEGylation procedures. Herein, we combine in vivo noncanonical amino acid (ncAA) incorporation and chemoselective conjugation in vitro to produce novel hybrid protein-dendrimer conjugates with the defined architectures. We incorporated Azidohomoalanine (Aha) as methionine substitute in vivo into various protein scaffolds to allow non-invasive dendrimer conjugations (dendronylation). Our approach makes recombinant proteins accessible for the design of multivalent dendrimer conjugates since it enables the preparation of many sequences with various positions for regioselective dendronylation.

Aggregation behaviour of non‐ionic twinned amphiphiles and their application as biomedical nanocarriers

A new class of twinned amphiphiles was developed by conjugating a pair of hydrophilic head groups from mPEG chains (Mn : 350 or 1000) and a pair of hydrophobic segments from linear alkyl chains (C11 or C18 ) through a novel spacer synthesized from glycerol and p-hydroxybenzoic acid. The aggregation phenomena of the amphiphiles were proven by DLS and fluorescence experiments, whereas size and morphology of the aggregates were evaluated by cryo-TEM. The measurements proved the formation of globular, thread-like or rod-like micelles as well as planar double-layer assemblies, depending on the amphiphiles molecular structure. The applicability of these non-ionic amphiphilic systems as nanocarriers for hydrophobic guest molecules was demonstrated by encapsulating a hydrophobic dye, Nile Red, and a hydrophobic drug, Nimodipine. The transport capacity results for both Nimodipine and Nile Red prove them as a promising candidate for drug delivery.

Supramolecular Copolymerization as a Strategy to Control the Stability of Self‐Assembled Nanofibers

A major challenge in supramolecular polymerization is controlling the stability of the polymers formed, that is, controlling the rate of monomer exchange in the equilibrium between monomer and polymer. The exchange dynamics of supramolecular polymers based on benzene-1,3,5-tricarboxamide (BTA) can be regulated by copolymerizing molecules with dendronized (dBTA) and linear (nBTA) ethylene glycol-based water-soluble side chains. Whereas nBTAs form long nanofibers in water, dBTAs do not polymerize, forming instead small spherical aggregates. The copolymerization of the two BTAs results in long nanofibers. The exchange dynamics of both the BTA monomers in the copolymer are significantly slowed down in the mixed systems, leading to a more stable copolymer, while the morphology and spectroscopic signature of the copolymers are identical to that of nBTA homopolymer. This copolymerization is the supramolecular counterpart of styrene/ maleic anhydride copolymerization.