We report here a controllable shape transformation of polymer vesicles (polymersomes) constructed from block copolymers of which the hydrophobic part is a high-molecular-weight glassy segment. Control over the shape transformation is obtained by kinetic manipulation of the phase behavior of this glassy hydrophobic segment. Kinetic manipulation of the phase behavior of polymer membranes allows for different shapes of polymersomes to be captured at specific times, which directly translates into physically robust nanostructures that are otherwise unobtainable. Combining the morphological diversity of giant liposomes and the physical robustness of polymersomes, our finding can be a general way to realize unusual nanostructures in a predictable manner.

A rapid and efficient approach for the preparation and modification of a versatile class of functional polymer nanoparticles has been developed, for which the entire engineering process from small molecules to polymers to nanoparticles bypasses typical slow and inefficient procedures, and rather employs a series of steps that capture fully the “click” chemistry concepts that have greatly facilitated the preparation of complex polymer materials over the past decade. The construction of various nanoparticles with functional complexity from a versatile platform is a challenging aim to provide materials for fundamental studies and also optimization toward a diverse range of applications. In this paper, we demonstrate the rapid and facile preparation of a family of nanoparticles with different surface charges and functionalities based on a biodegradable polyphosphoester block copolymer system. From a retrosynthetic point of view, the non-ionic, anionic, cationic and zwitterionic micelles with hydrodynamic diameters between 13 nm to 21 nm and great size uniformity were quickly formed by suspending, independently, four amphiphilic diblock polyphosphoesters into water, which were functionalized from the same parental hydrophobic-functional AB diblock polyphosphoester by “click” type thiol-yne reactions. The well-defined (PDI < 1.2) hydrophobic-functional AB diblock polyphosphoester was synthesized by an ultrafast (< 5 min) organocatalyzed ring-opening polymerization in a two-step, one-pot manner with the quantitative conversions of two kinds of cyclic phospholane monomers. The whole programmable process starting from small molecules to nanoparticles could be completed within 6 h, as the most rapid approach for the anionic and non-ionic nanoparticles, although the cationic and zwitterionic nanoparticles required ca. 2 days due to purification by dialysis. The micelles showed high biocompatibility, with even the cationic micelles exhibiting a 6-fold lower cytotoxicity toward RAW 264.7 mouse macrophage cells, as compared to the Lipofectamine® commercial transfection agent.

Devices resident in the stomach --which are used for a variety of clinical applications including nutritional modulation for bariatrics, ingestible electronics for diagnosis and monitoring, and gastric retentive dosage forms for prolonged drug delivery --typically incorporate elastic polymers to compress the devices during delivery through the esophagus and other narrow orifices in the digestive system. However, in the event of accidental device fracture or migration, the nondegradable nature of these materials risks intestinal obstruction. Here, we show that an elastic, pHresponsive supramolecular gel remains stable and elastic in the acidic environment of the stomach but can be dissolved in the neutral-pH environment of the small and large intestines. In a large Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use

Researchers strive to produce nanoparticles with complexity in composition and structure. Although traditional spherical, cylindrical and membranous, or planar, nanostructures are ubiquitous, scientists seek more complicated geometries for potential functionality. Here we report the simple solution construction of multigeometry nanoparticles, disk-sphere and diskcylinder, through a straightforward, molecular-level, blending strategy with binary mixtures of block copolymers. The multigeometry nanoparticles contain disk geometry in the core with either spherical patches along the disk periphery in the case of disk-sphere particles or cylindrical edges and handles in the case of the disk-cylinder particles. The portions of different geometry in the same nanoparticles contain different core block chemistry, thus also defining multicompartments in the nanoparticles. Although the block copolymers chosen for the blends are important for the definition of the final hybrid particles, the control of the kinetic pathway of assembly is critical for successful multigeometry particle construction.

The directed or dynamic assembly of molecular components in solution is a simple and effective strategy to confine materials in desired geometries and length scales. We use a kinetic control strategy with block copolymer blending to construct complex nanoparticles through the demixing of unlike block copolymers within the same nanoscale particle. Successful nanoparticle construction relies on kinetic trapping of unlike block copolymers into the same nanoparticle with solution processing. Not only can we make nanoparticles with multiple internal compartments of a desired size, but we can also make nanoparticles of hybrid geometries (e.g. a blend of cylindrical and spherical geometries). These combination particles are kinetically trapped, non-equilibrium structures. However, the block copolymers are able to phase separate locally within the nanoscale particle, thus producing internal compartments and hybrid geometries.

Block copolymer micelles (BCMs) were prepared from amphiphilic diblock copolymers of poly(n-butyl acrylate) and poly(acrylic acid) partially modified with 2-hydroxyethyl acrylate. Radical polymerization of acrylamide in the presence of micellar crosslinkers gave rise to elastomeric hydrogels (BCM-PAAm) whose mechanical properties can be tuned by varying the BCM composition. Transmission electron microscopy (TEM) imaging revealed stretch-induced, reversible micelle deformation in BCM-PAAm gels. A model hydrophobic drug, pyrene, loaded into the micelle core prior to the formation of BCM-PAAm gels, was dynamically released in response to externally applied mechanical forces. The BCM-crosslinked hydrogels with combined strength and force-modulated drug release are attractive candidates for the repair and regeneration of mechanically-active tissues.

Amphiphlic block copolymers consisting of hydrophilic, poly(acrylic acid) randomly decorated with acrylate groups and hydrophobic, rubbery poly(n-butyl acrylate) self-assembled into welldefined micelles with an average diameter of ~21 nm. Radical polymerization of acrylamide in the presence of the crosslinkable micelles gave rise to hybrid, elastomeric hydrogels whose mechancial properties can be readily tuned by varying the BCM concentration.Hydrogels are macroscopic, polymeric networks that imbibe large amount of water. Due to their biocompatibility, tissue-like viscoelasticity and structural similarity to the native extracelluar matrices (ECM), hydrogels are widely used in tissue engineering and drug delivery applications. [1][2][3] Traditional hydrogels are derived from molecularly-dispersed, soluble precursors (monomers and multifunctional crosslinkers or macromers) that are randomly interconnected, lacking the structural complexity, mechanical integrity and functional diversity seen in the natural ECM. 4 Novel hybrid hydrogels with hierarchical structures and robust mechanical properties have been synthesized using organic or inorganic particles of nano or micron dimensions as the constituent building blocks or multifunctional crosslinkers. For example, nanocomposite hydrogels with unprecedented mechanical strength have been constructed by initiating radical polymerization from the surface of clay nanoparticles. The unique mechanical properties were attributed to the reduced fluctuation in the crosslinking density and the cooperativity of the polymer chains connecting the same clays. 5,6 Soft hydrogel particles have also been exploited as the multifunctional, microscopic crosslinkers. 7-10 Our group has created hyaluronic acid (HA)-based doubly crosslinked networks with densely crosslinked, nanoporous HA hydrogel particles covalently interconnected by a loose secondary network that is also HA-based. 11-15 Such hierarchically-structured hydrogels permit the controlled release of bone morphogenetic protein 2 (BMP-2) with reduced initial bursts over prolonged periods of time. 12 Block copolymer micelles (BCMs) are yet another class of microscopic, spherical objects consisting of a segregated hydrophobic interior and a stealth, hydrophilic corona that stablizes the assembled structure and interacts with the aqueous environment. 16 Unlike inorganic nanoparticles or covalently crosslinked hydrogel particles (microgels and nanogels), BCMs exhibit distinct core-shell structure, capable of sequestering hydrophobic molecules and modulating their release kinetics, thereby, extending their pharmacokinetics. 17 Although water-dispersed BCMs have been extensively explored as drug delivery vehicles, they have not been investigated as multifunctional, microscopic crosslinkers for the formation of elastomeric hydrogels with desirable pharmacological activities. We hypothesize that strategic integration of well-defined hydrophobic microdomains within the hydrogel matrix will not only provide a local depot for therap...

In order to expand the utility of current polymeric micellar systems, we have developed amphiphilic multiblock copolymers containing alternating blocks of poly(acrylic acid) and poly(styrene). Heterotelechelic poly(tert-butyl acrylate-b-styrene) diblock copolymers containing an α-alkyne and an ω-azide were synthesized by atom transfer radical polymerization (ATRP), allowing control over the molecular weight while maintaining narrow polydispersity indices. The multiblock copolymers were constructed by copper-catalyzed azide-alkyne cycloaddition of azide-alkyne end functional diblock copolymers which were then characterized by 1H NMR, FT-IR and SEC. The tert-butyl moieties of the poly(tert-butyl acrylate-b-styrene) multiblock copolymers were easily removed to form the poly(acrylic acid-b-styrene) multiblock copolymer ((PAA-PS)9), which contained up to 9 diblock repeats. The amphiphilic multiblock (PAA-PS)9 (Mn = 73.3 kg/mol) was self-assembled by dissolution into tetrahydrofuran and extensive dialysis against deionized water for 4 days. The critical micelle concentration (CMC) for (PAA-PS)9 was determined by fluorescence spectroscopy using pyrene as a fluorescent probe and was found to be very low at 2 × 10-4 mg/mL. The (PAA-PS)9 multiblock was also analyzed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The hydrodynamic diameter of the particles was found to be 11 nm. Discrete spherical particles were observed by TEM with an average particle diameter of 14 nm. The poly(acrylic acid) periphery of the spherical particles should allow for future conjugation of biomolecules.