Ionic nanoporous membranes from self-assembled liquid crystalline brush-like imidazolium triblock copolymers.

There is a need to generate mechanically and thermally robust ionic nanoporous membranes for separation and fuel cell applications. Herein, we report a general approach to the preparation of ionic nanoporous membranes through custom synthesis, self-assembly, and subsequent chemical manipulations of ionic brush block copolymers. We synthesized polynorbornene-based triblock copolymers containing imidazolium cations balanced by counter anions in the central block, side-chain liquid crystalline units, and sidechain polylactide end blocks. This unique platform comprises: (1) imidazolium/bis(trifluoromethanesulfonyl)imide (TFSI) as the middle block, which has an excellent ion-exchange ability, (2) cyanobiphenyl liquid crystalline end block, a sterically hindered hydrophobic segment, which is chemically stable and immune to hydroxide attack, (3) polylactide brush-like units on the other end block that is easily etched under mild alkaline conditions and (4) a polynorbornene backbone, a lightly crosslinked system that offers mechanical robustness. These membranes retain their morphology before and after backbone crosslinking as well as etching of polylactide sidechains. The ion exchange performance and dimensional stability of these membranes were investigated by water uptake capability and swelling ratio. Moreover, the length of the carbon spacer in the imidazolium/TFSI central block moiety endowed the membrane with improved ionic conductivity. The ionic nanoporous materials are unusual due to their singular thermal, mechanical, alkaline stability and ion transport properties. Applications of these materials include electrochemical actuators, solid-state ionic nanochannel biosensors, and ion-conducting membranes.

Fast Photoswitchable Order-Disorder Transitions in Liquid-Crystalline Block Co-oligomers.

Optically driven ordering transitions are rarely observed in macromolecular systems, often because of kinetic limitations. Here, we report a series of block co-oligomers (BCOs) that rapidly order and disorder at room temperature in response to optical illumination, and the absence thereof. The system is a triblock where rigid azobenzene (Azo) mesogens are attached to each end of a flexible siloxane chain. UV-induced trans-to-cis Azo isomerization, and vice versa in the absence of UV light, drive disordering and ordering of lamellar superstructures and smectic mesophases, as manifested by liquefaction and solidification of the material, respectively. The impacts of chemical structure on BCO self-assembly and photoswitching kinetics are explored by in situ microscopy and X-ray measurements for different mesogen end groups (NO2 or CN), and different carbon chain lengths (0C or 12C) between the siloxane and the mesogen. The presence of the 12C spacer leads to hierarchical ordering with smectic layers of mesogens existing alongside larger length-scale lamellae, versus only smectic ordering without the spacer. These hierarchically ordered BCOs display highly persistent lamellar sheets that contrast with the tortuous, low-persistence "fingerprint"-type structures seen in conventional block copolymers. The reordering kinetics upon removal of UV illumination are extremely rapid (<5 s). This fast response is due to the electron-withdrawing NO2 and CN, which facilitate cis-to-trans isomerization via thermal relaxation at room temperature without additional stimuli. This work elucidates structure-property relationships in photoswitching BCOs and advances the possibility of developing systems in which ordered nanostructures can be easily optically written and erased.

Self-assembled materials from cellulose nanocrystals conjugated with a thermotropic liquid crystalline moiety.

Manipulating molecular and supramolecular interactions within cellulose nanocrystals (CNCs) to introduce different levels of assemblies combined with multiple functionalities is required for the development of degradable smart materials from renewable resources. To attain hierarchical structures and stimuli-responsive properties, a new class of liquid crystalline cellulosic hybrid materials is synthesized. Herein, main-chain rigid-rod-like oxidized cellulose (CNC-COOH) is prepared from a Cellulose Whatman filter paper (Cellulose W.P.) by acid hydrolysis and oxidized using 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO). Thermotropic LC molecule, 4-cyano-4'-hydroxybiphenyl with a 12-methylene spacer (CB12-OH) is grafted onto the carboxylic acid group of CNC-COOH via Steglich esterification. The liquid crystalline functionalized CNCs cellulose nanocrystals (CNC-COO-CB12) are readily soluble in DMSO and ionic liquids. The extent of functionalization and structure of CNC-COO-CB12 are confirmed by solution-state 1H NMR and supported by other characterization techniques. We investigate the interplay of liquid crystalline orientational order of CNCs and cyanobiphenyl (CB12), and the supramolecular hydrogen bonding of CNCs within CNC-COO-CB12 and compare it with CNC-COOH. The introduction of thermotropic CB12 side chains onto rigid-rod CNCs shows the exclusive formation of smectic mesophases from the assemblies of CB12 with the absence of the cholesteric mesophase typically observed from CNC-COOH as verified by temperature-controlled SAXS (T-SAXS). This is further verified by UV-visible and SEM studies that show CNC-COO-CB12 forms smectic domains while CNC-COOH forms a visible light reflecting cholesteric mesophase in dried films. Thus, the interplay of liquid crystalline order of CNCs and CB12 and supramolecular hydrogen bonding of CNCs results in ordered, smectic-mesostructured CNCs for use in stimuli-responsive functional materials.

Stabilization and X-ray Attenuation of PEGylated Cholesterol/Polycaprolactone-Based Perfluorooctyl Bromide Nanocapsules for CT Imaging.

Contrast-enhanced X-ray computed tomography plays an important role in cancer imaging and disease progression monitoring. Imaging using radiopaque nanoparticle platforms can provide insights on the likelihood of nanoparticle accumulation and can enable image-guided therapies. Perfluorooctyl bromide (PFOB)-loaded nanocapsules designed for this purpose were stabilized using an in-house synthesized PEGylated polycaprolactone-based copolymer (PEG-b-PCL(Ch)) and compared with commercial polycaprolactone employing a Quality-by-Design approach. PFOB is a dense liquid, weakly polarizable, and immiscible in organic and aqueous solvents; thus, carefully designed formulations for optimal colloidal stabilization to overcome settling-associated instability are required. PFOB-loaded nanocapsules exhibited high PFOB loading due to the intrinsic properties of PEG-b-PCL(Ch). Settling and caking are major sources of instability for PFOB formulations. However, the PEG-b-PCL(Ch) copolymer conferred the nanocapsules enough steric impediment and polymer shell elasticity to settle without significant caking, increasing the overall colloidal stability of the formulation. Furthermore, a clear relationship between nanocapsule physical properties and X-ray attenuation was established. Nanocapsules were able to enhance the X-ray contrast in vitro as a function of PFOB loading. This nanocapsule-based platform is promising for future translational studies and image-guided tumor therapy due to its enhanced contrastability and optimal colloidal stability.

Controlling orientational order in block copolymers using low-intensity magnetic fields.

The interaction of fields with condensed matter during phase transitions produces a rich variety of physical phenomena. Self-assembly of liquid crystalline block copolymers (LC BCPs) in the presence of a magnetic field, for example, can result in highly oriented microstructures due to the LC BCP's anisotropic magnetic susceptibility. We show that such oriented mesophases can be produced using low-intensity fields (<0.5 T) that are accessible using permanent magnets, in contrast to the high fields (>4 T) and superconducting magnets required to date. Low-intensity field alignment is enabled by the addition of labile mesogens that coassemble with the system's nematic and smectic A mesophases. The alignment saturation field strength and alignment kinetics have pronounced dependences on the free mesogen concentration. Highly aligned states with orientation distribution coefficients close to unity were obtained at fields as small as 0.2 T. This remarkable field response originates in an enhancement of alignment kinetics due to a reduction in viscosity, and increased magnetostatic energy due to increases in grain size, in the presence of labile mesogens. These developments provide routes for controlling structural order in BCPs, including the possibility of producing nontrivial textures and patterns of alignment by locally screening fields using magnetic nanoparticles.

Reduced in vivo toxicity of doxorubicin by encapsulation in cholesterol-containing self-assembled nanoparticles.

We previously reported the development of an amphiphilic brush-like block copolymer composed of polynorbornene-cholesterol/polyethylene glycol (P(NBCh9-b-NBPEG)) that self-assembles in aqueous media to form long circulating nanostructures capable of encapsulating doxorubicin (DOX-NPs). Biodistribution studies showed that this formulation preferentially accumulates in tumor tissue with markedly reduced accumulation in the heart and other major organs. The aim of the current study was to evaluate the in vivo efficacy and toxicity of DOX containing self-assembled polymer nanoparticles in a mouse xenograft tumor model and compare its effects with the hydrochloride non-encapsulated form (free DOX). DOX-NPs significantly reduced the growth of tumors without inducing any apparent toxicity. Conversely, mice treated with free DOX exhibited significant weight loss, early toxic cardiomyopathy, acute toxic hepatopathy, reduced hematopoiesis and fatal toxicity. The improved safety profile of the polymeric DOX-NPs can be explained by the low circulating concentration of non-nanoparticle-associated drug as well as the reduced accumulation of DOX in non-target organs. These findings support the use of P(NBCh9-b-NBPEG) nanoparticles as delivery platforms for hydrophobic anticancer drugs intended to reduce the toxicity of conventional treatments.

Long circulating self-assembled nanoparticles from cholesterol-containing brush-like block copolymers for improved drug delivery to tumors.

Amphiphilic brush-like block copolymers composed of polynorbonene-cholesterol/poly(ethylene glycol) (P(NBCh9-b-NBPEG)) self-assembled to form a long circulating nanostructure capable of encapsulating the anticancer drug doxorubicin (DOX) with high drug loading (22.1% w/w). The release of DOX from the DOX-loaded P(NBCh9-b-NBPEG) nanoparticles (DOX-NPs) was steady at less than 2% per day in PBS. DOX-NPs were effectively internalized by human cervical cancer cells (HeLa) and showed dose-dependent cytotoxicity, whereas blank nanoparticles were noncytotoxic. The DOX-NPs demonstrated a superior in vivo circulation time relative to that of free DOX. Tissue distribution and in vivo imaging studies showed that DOX-NPs preferentially accumulated in tumor tissue with markedly reduced accumulation in the heart and other vital organs. The DOX-NPs greatly improved survival and significantly inhibited tumor growth in tumor-bearing SCID mice compared to that for the untreated and free DOX-treated groups. The results indicated that self-assembled P(NBCh9-b-NBPEG) may be a useful carrier for improving tumor delivery of hydrophobic anticancer drugs.

Dynamic magnetic field alignment and polarized emission of semiconductor nanoplatelets in a liquid crystal polymer.

Reconfigurable arrays of 2D nanomaterials are essential for the realization of switchable and intelligent material systems. Using liquid crystals (LCs) as a medium represents a promising approach, in principle, to enable such control. In practice, however, this approach is hampered by the difficulty of achieving stable dispersions of nanomaterials. Here, we report on good dispersions of pristine CdSe nanoplatelets (NPLs) in LCs, and reversible, rapid control of their alignment and associated anisotropic photoluminescence, using a magnetic field. We reveal that dispersion stability is greatly enhanced using polymeric, rather than small molecule, LCs and is considerably greater in the smectic phases of the resulting systems relative to the nematic phases. Aligned composites exhibit highly polarized emission that is readily manipulated by field-realignment. Such dynamic alignment of optically-active 2D nanomaterials may enable the development of programmable materials for photonic applications and the methodology can guide designs for anisotropic nanomaterial composites for a broad set of related nanomaterials.

Cholesteric mesophase based 1D photonic materials from self-assembly of liquid crystalline block and random terpolymers containing chromonic molecules.

We describe the influence of competing self-organizing phenomena on the formation of cholesteric mesophase in liquid crystalline brush block terpolymers (LCBBTs) and liquid crystalline random brush terpolymers (LCRBTs) containing chromonic molecules. A library of LCBBTs and LCRBTs are synthesized using ring-opening metathesis polymerization (ROMP) of norbornene side-chain functionalized monomers comprising cholesteryl mesogen (NBCh9), chromonic xanthenone (NBXan), and poly(ethylene glycol) (NBMPEG). Compression molded films of LCRBTs containing chromonic molecules display multilevel hierarchical structure in which cholesteric mesophase co-exists with π-π stacking of the chromonic mesophase along with PEG microphase segregated domains. This is unexpected as conventional LCBCPs and LCBBCs that lack chromonic molecules do not form cholesteric mesophases. The presence of π-π interactions modifies the interface at the IMDS so that both chromonic and cholesteric mesophases coexist leading to the manifestation of cholesteric phase for the first time within block architecture and is very reminiscent of previously published LCRBCs without chromonic molecules. The key to the observed hierarchical assembly in these LCBBTs containing chromonic molecules lies in the interplay of LC order, chromonic π-π stacking, PEG side chain microphase segregation, and their supramolecular cooperative motion. This unique "single component" polymer scaffold transforms our capacity to attain nanoscale hierarchies and optical properties from block architecture similar to nanoscale mesophases resulting in random architecture.

Influence of the method of preparation on the characteristics and performance of cholesterol-based polymeric nanoparticles for redox-triggered release of doxorubicin in tumor cells.

Immature manufacturing and sub-optimal control of quality attributes hinder the effective translation of nanoformulations for cancer treatment, being partially responsible for the scarce number of products on the market. The effect of the method of preparation on the performance of complex formulations such as bio-responsive nanomedicines needs further understanding. In this study, we investigated the the influence of the method of preparation on the characteristics and bio-responsiveness of doxorubicin-loaded redox-sensitive nanoparticles (DOX-SS-NPs), formed by a biocompatible cholesterol-based amphiphilic block copolymer (PC5MA-SS-PEO). Two commonly used preparation techniques: (1) cosolvent removal and (2) an O/W emulsion method were compared and the in vitro and in vivo performance of promising formulations was assessed. Besides particle size distribution and drug loading, the response of the nanoparticles to reducing environments and subsequent release kinetics and cytotoxicity were also affected by the method of preparation. The investigation and understanding of this extensive influence, led to a DOX-SS-NPs formulation with significant in vivo efficacy and an improved safety profile when evaluated against free doxorubicin (DOX-HCl) and the commercial pegylated liposomal form (Doxil®). Our findings highlight the importance of formulation optimization and support the use of systematic approaches like Quality by Design to the development of bio-responsive nanomedicines for cancer treatment.