Supramolecular Disassembly of Facially Amphiphilic Dendrimer Assemblies in Response to Physical, Chemical, and Biological Stimuli

Abstract

ConspectusSupramolecular assemblies formed from spontaneous self-assembly of amphiphilic macromolecules are explored as biomimetic architectures and for applications in areas such as sensing, drug delivery, and diagnostics. Macromolecular assemblies are usually preferred, compared with their simpler small molecule counterparts, due to their low critical aggregate concentrations (CAC) and high thermodynamic stability. This Account focuses on the structural and functional aspects of assemblies formed from dendrimers, specifically facially amphiphilic dendrons that form micelle or inverse micelle type supramolecular assemblies depending on the nature of the solvent medium.The micelle type assemblies formed from facially amphiphilic dendrons sequester hydrophobic guest molecules in their interiors. The stability of these assemblies is dependent on the relative compatibility of the hydrophilic and hydrophobic functionalities with water, often referred to as hydrophilic–lipophilic balance (HLB). Disruption of the HLB, using an external stimulus, could lead to disassembly of the aggregates, which can then be utilized to cause an actuation event, such as guest molecule release. Studying these possibilities has led to (i) a robust and general strategy for stimulus-induced disassembly and molecular release and (ii) the introduction of a new approach to protein-responsive supramolecular disassembly. The latter strategy provides a particularly novel avenue for impacting biomedical applications. Most of the stimuli-sensitive supramolecular assemblies have been designed to be responsive to factors such pH, temperature, and redox conditions. The reason for this interest stems from the fact that certain disease microenvironments have aberrations in these factors. However, these variations are the secondary imbalances in biology. Imbalances in protein activity are the primary reasons for most, if not all, human pathology. There have been no robust strategies in stimulus-responsive assemblies that respond to these variations. The facially amphiphilic dendrimers provide a unique opportunity to explore this possibility.Similarly, the propensity of these molecules to form inverse micelles in apolar solvents and thus bind polar guest molecules, combined with the fact that these assemblies do not thermodynamically equilibrate in biphasic mixtures, was used to predictably simplify peptide mixtures. The structure–property relationships developed from these studies have led to a selective and highly sensitive detection of peptides in complex mixtures. Selectivity in peptide extraction was achieved using charge complementarity between the peptides and the hydrophilic components present in inverse micellar interiors. These findings will have implications in areas such as proteomics and biomarker detection.

Multifunctional triazolylferrocenyl Janus dendron: Nanoparticle stabilizer, smart drug carrier and supramolecular nanoreactor

“…Amphiphilic Janus dendrimers and dendrons feature various well‐defined and complex self‐assembled structures such as micelles, vesicles, cubosomes, discs, tubular vesicles, helical ribbons and bilayered vesicles called dendrimersomes, and their potential applications for drug delivery . Redox‐responsive Fc‐containing macromolecules have recently gained considerable attention due to their potential in controllable delivery and release in physiological environments, where redox reactions are widely and constantly present .…”

“…Janus dendrimers (JDs) are newly emerging types of dendrimers and are normally constructed of two different dendrons with varying size and functionality to obtain a single amphiphilic or heterofunctional macromolecule . Their asymmetric structures lead to new and efficient characteristic properties for the formation of complex self‐assembled materials that are presently inconceivable for homogeneous or symmetric dendrimers, and many applications have been investigated, especially in the fields of materials and biology, such as thermal actuators, ionic liquids, catalysis, light harvesting systems, bioimaging, optoelectronics and drug delivery …”

Diverse Applications of Nanomedicine

“…Drug encapsulation can be realized in unimolecular micelles or in supramolecular assemblies. 332 This approach enables encapsulation of the most widely used chemotherapeutic agents, e.g. , DOX, methotrexate, paclitaxel, and campthothecin.…”

Experimental and theoretical investigations in stimuli responsive dendrimer-based assemblies

“…Protein-induced disassembly of dendron assemblies in solution, due to a specific binding between complementary ligand-protein pairs such as biotin-avidin and 2, 4 DNP- Anti DNP IgG is well established in our research groups. 32 The change in the hydrophilic lipophilic balance (HLB) upon protein binding was hypothesized to be the driving force for disassembly. The ligand placement had a significant role in encapsulation efficiency, but its role in disassembly needed to be understood.…”