Crystallization processes are in general sensitive to detailed conditions, but our present understanding of underlying mechanisms is insufficient. A crystallizable chain within a diblock copolymer assembly is expected to couple curvature to crystallization and thereby impact rigidity as well as preferred morphology, but the effects on dispersed phases have remained unclear. The hydrophobic polymer polycaprolactone (PCL) is semi-crystalline in bulk (T m = 60°C) and is shown here to generate flexible worm micelles or rigid vesicles in water from several dozen polyethyleneoxide-based diblocks (PEO-PCL). Despite the fact that `worms' have a mean curvature between that of vesicles and spherical micelles, `worms' are seen only within a narrow, process-dependent wedge of morphological phase space that is deep within the vesicle phase. Fluorescence imaging shows worms are predominantly in one of two states -either entirely flexible with dynamic thermal undulations or fully rigid; only a few worms appear rigid at room temperature (T << T m ), indicating suppression of crystallization by both curvature and PCL hydration. Worm rigidification, which depends on molecular weight, is also prevented by copolymerization of caprolactone with just 10% racemic lactide that otherwise has little impact on bulk crystallinity. In contrast to worms, vesicles of PEO-PCL are always rigid and typically leaky. Defects between crystallite domains induce dislocation-roughening with focal leakiness although select PEO-PCL -which classical surfactant arguments would predict make worms -yield vesicles that retain encapsulant and appear smooth, suggesting a gel or glassy state. Hydration in dispersion thus tends to selectively soften high curvature microphases.Keywords block copolymer; worm micelle; polymersome; crystallinity Corresponding: discher@seas.upenn.edu. Supporting Information. Molecular details of all polymers synthesized, calculation of polymer distribution in assemblies, AFM and fluorescence microscopy images, DLS and dye encapsulation studies, movies of worm micelles, persistence length measurement of worm micelles, procedure for measurement of contour lengths, and phase contrast images of OCL (2, 13.5) can be found in Supporting Information. Supporting Information is available free of charge on the internet at

Nanoparticle shape can improve drug delivery, based in part on recent findings that flexible, worm-like nanocarriers (Worms) increase the amount of drug delivered to tumors and shrink the tumors more effectively than spherical micelles (Spheres). Here, all-atom molecular dynamics (MD) simulations are used to build a rational coarse grain (rCG) model that helps clarify shape-dependent effects in delivery of the widely used anticancer drug Taxol by block copolymer micelles. Potentials for rCG-MD were developed to examine the partitioning of this hydrophobic-aromatic drug into Worms and Spheres that self-assemble in water from poly(ethyleneglycol)-poly(caprolactone) (PEG-PCL), a weakly segregating amphiphile. PCL is a biodegradable, hydrophobic polymer widely used in biomaterials and accurately modeled here. Thermodynamic integration of the force to pull a single Taxol molecule from the micelles into solvent shows that twice as much drug loads into Worms than Spheres, fully consistent with experiments. Diffusivity of drug in the hydrated PEG corona is surprisingly slow compared to that in the core, indicative of strong but transient drug-polymer interactions. The distinctly distended corona of the Worms enhances such interactions and reflects the same balance of molecular forces that underlie an experimentally-validated phase diagram for simulated Spheres, Worms, and Bilayers. Moreover, with realistic drug loadings in micro-second simulations, Taxol is seen to draw PEG chains into the PCL core, dispersing the drug while localizing it near the interface—thus providing a molecular explanation for a measurable burst release of drug as well as the enhanced delivery seen with Worms.

While a great diversity of peptide-based supra-molecular filaments have been reported, the impact of an auxiliary segment on the chiral assembly of peptides remains poorly understood. Herein we report on the formation of chiral filaments by the self-assembly of a peptide-drug conjugate containing an aromatic drug camptothecin (CPT) in a computational study. We find that the chirality of the filament is mediated by the π‒π stacking between CPTs, not only by the well-expected intermolecular hydrogen bonding between peptide segments. Our simulations show that π‒π stacking of CPTs governs the early stages of the self-assembly process, while a hydrogen bonding network starts at a relatively later stage to contribute to the eventual morphology of the filament. Our results also show the possible presence of water within the core of the CPT filament. These results provide very useful guiding principles for the rational design of supramolecular assemblies of peptide conjugates with aromatic segments.