It has been shown by us in a recent communication that homopolymers, in which each repeat unit contains a hydrophilic and a hydrophobic head group, are capable of forming environment dependent micellar or inverse micellar assemblies. A systematic structure-property relationship study is carried out here to test the scope of the design. We show here that the molecular design is indeed broadly applicable and that there is a significant gain in the critical aggregation concentrations of these polymers, compared to the small molecule counterparts. We also show that the design can be tuned to achieve vesicle-type assemblies, which further expands the repertoire of amphiphilic homopolymers in a variety of areas. Characterizations of these assemblies have been carried out using transmission electron microscopy, dynamic light scattering, static light scattering, and dye incorporation experiments.

This review highlights the developments in dendrimer-based micelles for drug delivery. Dendrimers, the perfectly branched monodisperse macromolecules, have certain structural advantages that make them attractive candidates as drug carriers for controlled release or targeted delivery. As polymeric micelle-based approaches precede the work in dendrimers, these are also discussed briefly. The review concludes with a perspective on possible applications of biaryl-based dendrimeric micelles that exhibit environment-dependent conformations, in drug delivery.

Management of metastatic disease is integral to cancer treatment. Evaluation of metastases often requires surgical removal of all anatomically susceptible lymph nodes for ex vivo pathologic examination. We report a family of novel ratiometric activatable cell-penetrating peptides, which contain Cy5 as far red fluorescent donor and Cy7 as near-infrared fluorescent acceptor. Cy5 is quenched in favor of Cy7 reemission until the intervening linker is cut by tumor-associated matrix metalloproteinases-2 and 9 (MMP2,9) or elastases. Such cleavage increases the Cy5:Cy7 emission ratio 40-fold and triggers tissue retention of the Cy5-containing fragment. This ratiometric increase provides an accelerated and quantifiable metric to identify primary tumors and metastases to liver and lymph nodes with increased sensitivity and specificity. This technique represents a significant advance over existing nonratiometric protease sensors and sentinel lymph node detection methods, which give no information about cancer invasion.

A hydrogen peroxide (H2O2)-activated cell-penetrating peptide was developed through incorporation of a boronic acid-containing cleavable linker between polycationic cell-penetrating peptide and polyanionic fragments. Fluorescence labeling of the two ends of the molecule enabled monitoring its reaction with H2O2 through release of the highly adhesive cell-penetrating peptide and disruption of fluorescence resonance energy transfer. The H2O2 sensor selectively reacts with endogenous H2O2 in cell culture to monitor the oxidative burst of promyelocytes and in vivo to image lung inflammation. Targeting H2O2 has potential applications in imaging and therapy of diseases related to oxidative stress.

Syntheses up to three generations have been achieved of biaryl-based amphiphilic dendrons with a charge-neutral pentaethylene glycol as the hydrophilic part and a decyl chain as the hydrophobic part. Studies on the temperature-dependent characteristics revealed that these dendrons exhibit a generation-dependent lower critical solution temperature (LCST). This behavior is attributed to the combination of the amphipathic nature of the hydrophilic pentaethylene glycol side chain and dendritic effect. Interestingly, this biaryl-based scaffold also maintains the ability to form a micelle-like assembly in polar solvents and an inverted micelle-like assembly in apolar solvents. Polarity of the dendritic interior was investigated using dye-based microenvironment studies. The aggregation behavior of these micelles was analyzed by fluorescence spectroscopy and dynamic light scattering. Critical micelle concentrations (CMC) of these assemblies were investigated using fluorescence excitation spectra of the sequestered guest molecule, pyrene.

Recognition of small organic molecules and large biomolecules such as proteins is of great importance in pharmaceutical as well as biological applications. Recognition inside a nanoporous membrane is particularly attractive, because of the advantages associated with ligand-receptor interactions in confined spaces. Classical nanoporous membrane-based separations simply use the difference in size of the analytes relative to pore size in the membrane. In order to bring about selectivity beyond size, it is necessary that methods for functionalizing the membrane pores are readily available. Here, we describe a simple approach to functionalize the nanopores within these membranes using self-assembling and non-self-assembling polymers. We show that these modified membranes separate small molecules based on size, charge and hydrophobicity. We also demonstrate here that proteins can be differentially transported through the nanopores based on their size and/or electrostatics.

A simple strategy for pattern recognition of proteins through micellar disassembly is introduced. Five different noncovalently assembled receptors have been generated, and the disassembly was studied by monitoring the encapsulated dye release in response to five different proteins. The disassembly induced fluorescence change of the guest molecule produces protein-specific patterns.

In real time: Thrombin activation in vivo can be imaged in real time with ratiometric activatable cell penetrating peptides (RACPPs). RACPPs are designed to combine 1) dual‐emission ratioing, 2) far red to infrared wavelengths for in vivo mammalian imaging, and 3) cleavage‐dependent spatial localization. The most advanced RACPP uses norleucine (Nle)‐TPRSFL as a linker that increases sensitivity to thrombin by about 90‐fold (see figure).