Oligoethylene glycol decorated supramolecular assemblies have been of great interest due to their charge-neutral character and thus the propensity to avoid non-specific interactions. These systems are known to exhibit a macroscopic temperature-sensitive transition, where the assembly phase-separates from the aqueous phase at higher temperatures. While this so-called lower critical solution temperature (LCST) behavior has been well-studied, there have been no studies on the fate of these supramolecular assemblies below this transition temperature. The work here brings to light the presence of a second, sub-LCST transition, observed well below the LCST of oligoethylene glycol (OEG) based dendrons, where the host-guest properties of the assembly are significantly altered. This sub-LCST transition is accompanied by changes in the guest encapsulation stability and dynamics of host exchange.

Reverse-micelle forming amphiphilic homopolymers with carboxylic acid and quaternary amine substituents are used to selectively enrich biomarker peptides and protein fragments from human serum prior to matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis. After depletion of human serum albumin (HSA) and immunoglobulin G (IgG), low abundance peptide biomarkers can be selectively enriched and detected by MALDI-MS at clinically relevant concentrations by using the appropriate homopolymer(s) and extraction pH value(s). Three breast cancer peptide biomarkers, bradykinin, C4a, and ITIH4, were chosen to test this new approach, and detection limits of 0.5 ng/mL, 0.08 ng/mL, and 0.2 ng/mL, respectively, were obtained. In addition, the amphiphilic homopolymers were used to detect prostate specific antigen (PSA) at concentrations as low as 0.5 ng/mL by targeting a surrogate peptide fragment of this protein biomarker. Selective enrichment and sensitive MS detection of low abundance peptide/protein biomarkers by these polymeric reverse micelles should be a sensitive and straightforward approach for biomarker screening in human serum.

In the past decade, there has been an increasing interest in supramolecular systems that can undergo physical or chemical tranformations upon encountering a specific stimulus. Micelle-forming amphiphilic systems based on polymers and dendrimers are particularly preferred over small molecule amphiphiles, due to their ability to sequester and release a vast library of hydrophobic guest molecules at micromolar polymer or dendrimer concentrations. Here we review a relatively underexplored, yet rapidly advancing, field of amphiphilic systems based on dendritic architechture that exhibit stimuli sensitive behaviour. In particular, we will be focusing on stimuli such as temperature, pH, enzymatic and non-enzymatic proteins. These stimuli-responsive systems offer a unique opportunity in the field of drug delivery and sensing.

Zwitterionic amphiphilic homopolymers can be conveniently prepared in one-pot using activated ester-based polymer precursors. We show that these zwitterionic polymers can (i) spontaneously self-assemble to form micelle-like and inverse micelle-like assemblies depending on the solvent environment; (ii) act as hydrophilic and hydrophobic nanocontainers in apolar and polar solvents respectively; (iii) undergo pH-responsive surface charge and size variations; (iv) exhibit least cytotoxicity compared to structurally analogous amphiphilic homopolymers.

Supramolecular assemblies formed by amphiphilic homopolymers with negatively charged groups in the hydrophilic segment have been designed to enable high labeling selectivity towards reactive side chain functional groups in peptides. The negatively-charged interiors of the supramolecular assemblies are found to block the reactivity of protonated amines that would otherwise be reactive in aqueous solution, while maintaining the reactivity of non-protonated amines. Simple changes to the pH of the assemblies’ interiors allow control over the reactivity of different functional groups in a manner that is dependent on the pKa of a given peptide functional group. The labeling studies carried out in positively charged supramolecular assemblies and free buffer solution show that, even when the amine is protonated, labeling selectivity exists only when complementary electrostatic interactions are present, thereby demonstrating the electrostatically controlled nature of these reactions.