Enzyme-responsive micelles have great potential as drug delivery platforms due to the high selectivity of the activating enzymes. Here we report a highly modular design for the efficient and simple synthesis of amphiphilic block copolymers based on a linear hydrophilic polyethyleneglycol (PEG) and an enzyme-responsive hydrophobic dendron. These amphiphilic hybrids self-assemble in water into micellar nanocontainers that can disassemble and release encapsulated molecular cargo upon enzymatic activation. The utilization of monodisperse dendrons as the stimuli-responsive block enabled a detailed kinetic study of the molecular mechanism of the enzymatically triggered disassembly. The modularity of these PEG-dendron hybrids allows control over the disassembly rate of the formed micelles by simply tuning the PEG length. Such smart amphiphilic hybrids could potentially be applied for the fabrication of nanocarriers with adjustable release rates for delivery applications.

No abstract

The high selectivity and often-observed overexpression of specific disease-associated enzymes make them extremely attractive for triggering the release of hydrophobic drug or probe molecules from stimuli-responsive micellar nanocarriers. Here we utilized highly modular amphiphilic polymeric hybrids, composed of a linear hydrophilic polyethylene glycol (PEG) and an esterase-responsive hydrophobic dendron, to prepare and study two diverse strategies for loading of enzyme-responsive micelles. In the first type of micelles, hydrophobic coumarin-derived dyes were encapsulated noncovalently inside the hydrophobic core of the micelle, which was composed of lipophilic enzyme-responsive dendrons. In the second type of micellar nanocarrier the hydrophobic molecular cargo was covalently linked to the end-groups of the dendron through enzyme-cleavable bonds. These amphiphilic hybrids self-assembled into micellar nanocarriers with their cargo covalently encapsulated within the hydrophobic core. Both types of micelles were highly responsive toward the activating enzyme and released their molecular cargo upon enzymatic stimulus. Importantly, while faster release was observed with noncovalent encapsulation, higher loading capacity and slower release rate were achieved with covalent encapsulation. Our results clearly indicate the great potential of enzyme-responsive micellar delivery platforms due to the ability to tune their payload capacities and release rates by adjusting the loading strategy.

Studying the enzymatic degradation of synthetic polymers is crucial for the design of suitable materials for biomedical applications ranging from advanced drug delivery systems to tissue engineering. One of the key parameters that governs enzymatic activity is the limited accessibility of the enzyme to its substrates that may be collapsed inside hydrophobic domains. PEG-dendron amphiphiles can serve as powerful tools for the study of enzymatic hydrolysis of polymeric amphiphiles due to the monodispersity and symmetry of the hydrophobic dendritic block, which significantly simplifies kinetic analyses. Using these hybrids, we demonstrate how precise, minor changes in the hydrophobic block are manifested into tremendous changes in the stability of the assembled micelles toward enzymatic degradation. The obtained results emphasize the extreme sensitivity of self-assembly and its great importance in regulating the accessibility of enzymes to their substrates. Furthermore, the demonstration that the structural differences between readily degradable and undegradable micelles are rather minor, points to the critical roles that self-assembly and polydispersity play in designing biodegradable materials.

A modified approach toward synthesizing colloidal CoFe 2 O 4 nanocrystals, using mixed types of organometallic precursors, is presented and compared to CoFe 2 O 4 nanocrystals that have been produced according to previously reported synthetic techniques. Although the standard characterization techniques, such as electron microscopy, energy-dispersive X-ray spectroscopy, magnetometry, Fourier transform infrared spectroscopy, and X-ray diffraction, provided similar results for nanocrystals from three different syntheses, magneto-optical (MO) spectroscopy is the only technique that has revealed significant differences between these preparation techniques. The MO spectra displayed substantial differences in the incorporation of Co 2+ ions within the ferrite crystal structure, making it a unique probe for optimizing the synthesis of stoichiometrically and structurally precise cobalt-ferrite nanoparticles.