Fracture formation due to drying is a common process in a range of systems, from mud cracks to thin polymeric films. Design and control of the fracturing process can be used as a tool for directing the fractures into predefined paths, leading to patterning and controlled fragmentation. In this work, we report the spontaneous periodic fragmentation of polymeric microfibers upon drying. The microfibers are fabricated via electrospinning of amphiphilic triblock copolymers over a glass substrate, and throughout their drying, highly periodic and sharp transverse cracking occurs along the fiber, resulting in the production of anisotropic microparticles (MPs) with a remarkably narrow size distribution. The average length of the MPs depends on the fiber's diameter; hence, by tuning the diameter of the fibers, size control over the MPs is achieved. X-ray scattering measurements reveal the formation of a lamellar arrangement of the copolymers along the fiber, providing a molecular insight into the formation of sharp transverse fractures. Adjusting the lipophilicity of the two terminal hydrophobic dendritic blocks of the triblock copolymers allows tuning the solubility of the obtained MPs in water and the release rate of hydrophobic cargo, opening a new route for the fabrication of anisotropic MPs for controlled release applications.

Polymeric assemblies, such as micelles, are gaining increasing attention due to their ability to serve as nanoreactors for the execution of organic reactions in aqueous media. The ability to conduct organic transformations, which have been traditionally limited to organic media, in water is essential for the further development of important fields ranging from green catalysis to bioorthogonal chemistry. Considering the recent progress that has been made to expand the range of organometallic reactions conducted using nanoreactors, we aimed to gain a deeper understanding of the roles of the hydrophobicity of both the core of micellar nanoreactors and the substrates on the reaction rates in water. Toward this goal, we designed a set of five metal-loaded micelles composed of polyethylene glycol–dendron amphiphiles and studied their ability to serve as nanoreactors for a palladium-mediated depropargylation reaction of four substrates with different log P values. Using dendrons as the hydrophobic block, we could precisely tune the lipophilicity of the nanoreactors, which allowed us to reveal linear correlations between the rate constants and the hydrophobicity of the amphiphiles (estimated by the dendron’s cLog P ). While exponential dependence was obtained for the lipophilicity of the substrates, a similar degree of rate acceleration was observed due to the increase in the hydrophobicity of the amphiphiles regardless of the effect of the substrate’s log P . Our results demonstrate that while increasing the hydrophobicity of the substrates may be used to accelerate reaction rates, tuning the hydrophobicity of the micellar nanoreactors can serve as a vital tool for further optimization of the reactivity and selectivity of nanoreactors.

Enzyme-responsive polymeric micelles hold great potential as drug delivery systems due to the overexpression of disease-associated enzymes. To achieve selective and efficient delivery of their therapeutic cargo, micelles need to be highly stable and yet disassemble when encountering their activating enzyme at the target site. However, increased micellar stability is accompanied by a drastic decrease in enzymatic degradability. The need to balance between stability and enzymatic degradation has severely limited the therapeutic applicability of enzyme-responsive nanocarriers. Here, we report a general modular approach for designing stable enzyme-responsive micelles whose enzymatic degradation can be enhanced on demand. The control over their response to the activating enzyme is achieved by stimuli-induced splitting of triblock amphiphiles into two identical diblock amphiphiles, which have the same hydrophilic–lipophilic balance as the parent amphiphile. This architectural transition drastically affects the micelle–unimer equilibrium and therefore increases the sensitivity of the micelles toward enzymatic degradation. As a proof of concept, we designed UV- and reduction-activated splitting mechanisms, demonstrating the ability to use architectural transition as a tool for tuning amphiphile–protein interactions, providing a general solution toward overcoming the stability–degradability barrier for enzyme-responsive nanocarriers.

<p>Polymeric assemblies, such as micelles, are gaining increasing attention due to their ability to serve as nanoreactors for the execution of organic reactions in aqueous media. The ability to conduct transformations, which have been limited to organic media, in water is essential for the further development of the important fields of green</p><p>catalysis and bioorthogonal chemistry, among other fields. In light of the recent progress in the expanding the scopes of reactions that can be conducted using nanoreactors, we aimed to gain deeper understanding of the roles of the hydrophobicity of both the core of micellar nanoreactors and the substrates on the reaction rates in water. Towards this goal we designed a set of metal-loaded micelles, composed of PEG-dendron amphiphiles and studied their ability to serve as nanoreactors for a palladium mediated depropargylation reaction of four substrates with different LogP values. Using dendrons as the hydrophobic block, allowed us to fine tune the lipophilicity of the dendritic end-groups and study how precise structural changes in the hydrophobicity of the amphiphiles affect the reaction rates. The kinetic data revealed linear relations between the rate constants and the hydrophobicity of the amphiphiles (estimated by the dendron’s</p><p>cLogP), while exponential dependence was obtained for the lipophilicity of the substrates (estimated by their LogP values). Our results demonstrate the vital contributions of the hydrophobicity of both the substrates and amphiphiles on the lipo-selectivity of nanoreactors, illustrating the potential of tuning hydrophobicity as a tool for optimizing</p><p>the reactivity and selectivity of nanoreactors.</p>

Degradable polymeric micelles are promising drug delivery systems due to their hydrophobic core and responsive design. When applying micellar nanocarriers for tumor delivery, one of the bottlenecks encountered in vivo is the tumor tissue barrier: crossing the dense mesh of cells and extracellular matrix (ECM). Sometimes overlooked, the extracellular matrix can trap nanoformulations based on charge, size and hydrophobicity. Here we used a simple design of a microfluidic chip with two types of ECM and MCF7 spheroids to allow high throughput screening of the interactions between biological interfaces and polymeric micelles. To demostrarte the applicapility of the chip, a small library of fluorescently labelled polymeric micelles varying in their hydrophilic shell and hydrophobic core forming blocks was studied. Three widely used hydrophilic shells were tested and compared, poly(ethylene glycol), poly(2-ethyl-2-oxazoline), and poly(acrylic acid), along with two enzyamticaly degradable dendritic hydrophobic cores (based on Hexyl or Nonyl end-gorups). Using ratiometric imaging of unimer:micelle fluorescence and FRAP inside the chip model, we obtained the local assembly state and dynamics inside the chip. Notably, we observed different micelle behaviors in the basal lamina ECM, from avoidance of ECM structure to binding of the poly(acrylic acid) formulations. Binding to basal lamina correlated with higher uptake into MCF7 spheroids. Overall, we proposed a simple microfluidic chip containing dual ECM and spheroids for the assessment of the interactions of polymeric nanocarrires with biological interfaces and evaluating nanoformulations capacity to cross the tumor tissue barrier.