Customized Nanostructured Ceramics via Microphase Separation 3D Printing.

To date, the restricted capability to fabricate ceramics with independently tailored nano- and macroscopic features has hindered their implementation in a wide range of crucial technological areas, including aeronautics, defense, and microelectronics. In this study, a novel approach that combines self- and digital assembly to create polymer-derived ceramics with highly controlled structures spanning from the nano- to macroscale is introduced. Polymerization-induced microphase separation of a resin during digital light processing generates materials with nanoscale morphologies, with the distinct phases consisting of either a preceramic precursor or a sacrificial polymer. By precisely controlling the molecular weight of the sacrificial polymer, the domain size of the resulting material phases can be finely tuned. Pyrolysis of the printed objects yields ceramics with complex macroscale geometries and nanoscale porosity, which display excellent thermal and oxidation resistance, and morphology-dependent thermal conduction properties. This method offers a valuable technological platform for the simplified fabrication of nanostructured ceramics with complex shapes.

Effect of Macromolecular Structure on Phase Separation Regime in 3D Printed Materials.

In this study, the fabrication of 3D-printed polymer materials with controlled phase separation using polymerization induced microphase separation (PIMS) via photoinduced 3D printing is demonstrated. While many parameters affecting the nanostructuration in PIMS processes are extensively investigated, the influence of the chain transfer agent (CTA) end group, i.e., Z-group, of macromolecular chain transfer agent (macroCTA) remains unclear as previous research has exclusively employed trithiocarbonate as the CTA end group. Herein, the effect of macroCTAs containing four different Z-groups on the formation of nanostructure of 3D printed materials is explored. The results show that the different Z-groups lead to distinct network formation and phase separation behaviors between the resins, influencing both the 3D printing process and the resulting material properties. Specifically, less reactive macroCTAs toward acrylic radical addition, such as O-alkyl xanthate and N-alkyl-N-aryl dithiocarbamate, result in translucent and brittle materials with macrophase separation morphology. In contrast, more reactive macroCTAs such as S-alkyl trithiocarbonate and 4-chloro-3,5-dimethylpyrazo dithiocarbamate produce transparent and rigid materials with nano-scale morphology. Findings of this study provide a novel approach to manipulate the nanostructure and properties of 3D printed PIMS materials, which can have important implications for materials science and engineering.

Surface Inactivation of Highly Mutated SARS-CoV-2 Variants of Concern: Alpha, Delta, and Omicron.

Continued SARS-CoV-2 transmission among the human population has meant the evolution of the virus to produce variants of increased infectiousness and virulence, coined variants of concern (VOCs). The last wave of pandemic infections was driven predominantly by the delta VOC, but because of continued transmission and adaptive mutations, the more highly transmissible omicron variant emerged and is now dominant. However, due to waning immunity and emergence of new variants, vaccines alone cannot control the pandemic. The application of an antiviral coating to high-touch surfaces and physical barriers such as masks are an effective means to inactivate the virus and their spread. Here, we demonstrate an environmentally friendly water-borne polymer coating that can completely inactivate SARS-CoV-2 independent of the infectious variant. The polymer was designed to target the highly glycosylated spike protein on the virion surface and inactivate the virion by disruption of the viral membrane through a nano-mechanical process. Our findings show that, even with low amounts of coating on the surface (1 g/m2), inactivation of alpha, delta, and omicron VOCs and degradation of their viral genome were complete. Furthermore, our data shows that the polymer induces little to no skin sensitization in mice and is non-toxic upon oral ingestion in rats. We anticipate that our transparent polymer coating can be applied to face masks and many other surfaces to capture and inactivate the virus, aiding in the reduction of SARS-CoV-2 transmission and evolution of new variants of concern.

3D Printing Nanostructured Solid Polymer Electrolytes with High Modulus and Conductivity.

The development of advanced solid-state energy-storage devices is contingent upon finding new ways to produce and manufacture scalable, high-modulus solid-state electrolytes that can simultaneously provide high ionic conductivity and robust mechanical integrity. In this work, an efficient one-step process to manufacture solid polymer electrolytes composed of nanoscale ion-conducting channels embedded in a rigid crosslinked polymer matrix via Digital Light Processing 3D printing is reported. A visible-light-mediated polymerization-induced microphase-separation approach is utilized, which produces materials with two chemically independent nanoscale domains with highly tunable nanoarchitectures. By producing materials containing a poly(ethylene oxide) domain swelled with an ionic liquid, robust solid polymer electrolytes with outstanding room-temperature (22 °C) shear modulus (G' > 108 Pa) and ionic conductivities up to σ = 3 × 10-4 S cm-1 are achieved. The nanostructured 3D-printed electrolytes are fabricated into a custom geometry and employed in a symmetric carbon supercapacitor, demonstrating the scalability of the fabrication and the functionality of the electrolyte. Critically, these high-performance materials are manufactured on demand using inexpensive and commercially available 3D printers, which allows the facile modular design of solid polymer electrolytes with custom geometries.

Designing Nanostructured 3D Printed Materials by Controlling Macromolecular Architecture.

Nanostructured polymeric materials play important roles in many advanced applications, however, controlling the morphologies of polymeric thermosets remains a challenge. This work uses multi-arm macroCTAs to mediate polymerization-induced microphase separation (PIMS) and prepare nanostructured materials via photoinduced 3D printing. The characteristic length scale of microphase-separated domains is determined by the macroCTA arm length, while nanoscale morphologies are controlled by the macroCTA architecture. Specifically, using 2- and 4- arm macroCTAs provides materials with different morphologies compared to analogous monofunctional linear macroCTAs at similar compositions. The mechanical properties of these nanostructured thermosets can also be tuned while maintaining the desired morphologies. Using multi-arm macroCTAs can thus broaden the scope of accessible nanostructures for extended applications, including the fabrication of actuators and potential drug delivery devices.

Nano- to macro-scale control of 3D printed materials via polymerization induced microphase separation.

Although 3D printing allows the macroscopic structure of objects to be easily controlled, controlling the nanostructure of 3D printed materials has rarely been reported. Herein, we report an efficient and versatile process for fabricating 3D printed materials with controlled nanoscale structural features. This approach uses resins containing macromolecular chain transfer agents (macroCTAs) which microphase separate during the photoinduced 3D printing process to form nanostructured materials. By varying the chain length of the macroCTA, we demonstrate a high level of control over the microphase separation behavior, resulting in materials with controllable nanoscale sizes and morphologies. Importantly, the bulk mechanical properties of 3D printed objects are correlated with their morphologies; transitioning from discrete globular to interpenetrating domains results in a marked improvement in mechanical performance, which is ascribed to the increased interfacial interaction between soft and hard domains. Overall, the findings of this work enable the simplified production of materials with tightly controllable nanostructures for broad potential applications.

Temperature-Directed Formation of Anisotropic Kettlebell and Tadpole Nanostructures in the Absence of a Swelling-Induced Solvent.

Anisotropic Janus ("snowman") nanoparticles with a single protrusion are currently made via the solvent swelling-induced method. Here, we demonstrate without the aid of toxic solvents a generally applicable method for the formation of anisotropic polymer nanoparticles directly in water by controlling polymer mobility through tuning its glass transition temperature (Tg ). Spherical structures, formed immediately after the emulsion polymerization, transformed into uniform tadpoles (with head diameter ≈60 nm and tail length ≈130 nm) through the protrusion of a single cylindrical tail when cooled to a temperature above the Tg of the polymer. Cooling the spheres to below the Tg produced kinetically trapped kettlebell structures that could be freeze-dried and rehydrated without any structural change. These unique kettlebells could transform into uniform tadpoles by heating above the Tg , representing a triggered and on-demand structural reorganization.

Nanostructure Control in 3D Printed Materials.

Currently, there are no straightforward methods to 3D print materials with nanoscale control over morphological and functional properties. Here, a novel approach for the fabrication of materials with controlled nanoscale morphologies using a rapid and commercially available Digital Light Processing 3D printing technique is demonstrated. This process exploits reversible deactivation radical polymerization to control the in-situ-polymerization-induced microphase separation of 3D printing resins, which provides materials with complex architectures controllable from the macro- to nanoscale, resulting in the preparation of materials with enhanced mechanical properties. This method does not require specialized equipment or process conditions and thus represents an important development in the production of advanced materials via additive manufacturing.

Water-Borne Nanocoating for Rapid Inactivation of SARS-CoV-2 and Other Viruses.

The rise in coronavirus variants has resulted in surges of the disease across the globe. The mutations in the spike protein on the surface of the virion membrane not only allow for greater transmission but also raise concerns about vaccine effectiveness. Preventing the spread of SARS-CoV-2, its variants, and other viruses from person to person via airborne or surface transmission requires effective inactivation of the virus. Here, we report a water-borne spray-on coating for the complete inactivation of viral particles and degradation of their RNA. Our nanoworms efficiently bind and, through subsequent large nanoscale conformational changes, rupture the viral membrane and subsequently bind and degrade its RNA. Our coating completely inactivated SARS-CoV-2 (VIC01) and an evolved SARS-CoV-2 variant of concern (B.1.1.7 (alpha)), influenza A, and a surrogate capsid pseudovirus expressing the influenza A virus attachment glycoprotein, hemagglutinin. The polygalactose functionality on the nanoworms targets the conserved S2 subunit on the SARS-CoV-2 virion surface spike glycoprotein for stronger binding, and the additional attachment of guanidine groups catalyze the degradation of its RNA genome. Coating surgical masks with our nanoworms resulted in complete inactivation of VIC01 and B.1.1.7, providing a powerful control measure for SARS-CoV-2 and its variants. Inactivation was further observed for the influenza A and an AAV-HA capsid pseudovirus, providing broad viral inactivation when using the nanoworm system. The technology described here represents an environmentally friendly coating with a proposed nanomechanical mechanism for inactivation of both enveloped and capsid viruses. The functional nanoworms can be easily modified to target viruses in future pandemics, and is compatible with large scale manufacturing processes.

Therapeutic Delivery of Polymeric Tadpole Nanostructures with High Selectivity to Triple Negative Breast Cancer Cells.

Targeted delivery of therapeutic drugs using nanoparticles to the highly aggressive triple negative breast cancer cells has the potential to reduce side effects and drug resistance. Cell entry into triple negative cells can be enhanced by incorporating cell binding receptor molecules on the surface of the nanoparticles to enhance receptor-mediated entry pathways, including clatherin or caveolae endocytosis. However, for highly aggressive cancer cells, these pathways may not be effective, with the more rapid and high volume uptake from macropinocytosis or phagocytosis being significantly more advantageous. Here we show, in the absence of attached cell binding receptor molecules, that asymmetric polymer tadpole nanostructure coated with a thermoresponsive poly(N-isopropylacrylamide) polymer with approximately 50% of this polymer in a globular conformation resulted in both high selectivity and rapid uptake into the triple breast cancer cell line MDA-MB-231. We found that the poly(N-isopropylacrylamide) surface coating in combination with the tadpole's unique shape had an almost 15-fold increase in cell uptake compared to spherical particles with the same polymer coating, and that the mode of entry was most likely through phagocytosis. Delivery of the tadpole attached with doxorubicin (a prodrug, which can be released at pHs < 6) showed a remarkable 10-fold decrease in the IC50 compared to free doxorubicin. It was further observed that cell death was primarily through late apoptosis, which may allow further protection from the body's own immune system. Our results demonstrate that by tuning the chemical composition, polymer conformation and using an asymmetric-shaped nanoparticle, both selectivity and effective delivery and release of therapeutics can be achieved, and such insights will allow the design of nanoparticles for optimal cancer outcomes.

Temperature-Induced Formation of Uniform Polymer Nanocubes Directly in Water.

Conventional self-assembly methods of block copolymers in cosolvents (i.e., usually water and organic solvents) has yet to produce a pure and monodisperse population of nanocubes. The requirement to assemble a nanocube is for the second block to have a high molecular weight. However, such high molecular weight block copolymers usually result in the formation of kinetically trapped nanostructures even with the addition of organic cosolvents. Here, we demonstrate the rapid production of well-defined polymer nanocubes directly in water by utilizing the thermoresponsive nature of the second block (with 263 monomer units), in which the block copolymer was fully water-soluble below its lower critical solution temperature (LCST) and would produce a pure population of nanocubes when heated above this temperature. Incorporating a pH-responsive monomer in the second block allowed us to control the size of the nanocubes in water with pH and the LCST of the block copolymer. We then used the temperature and pH responsiveness to create an adaptive system that changes morphology when using a unique fuel. This fuel (H2O2 + MnO2) is highly exothermic, and the solution pH increases with the consumption of H2O2. Initially, a nonequilibrium spherical nanostructure formed, which transformed over time into nanocubes, and by controlling the exotherm of the reaction, we controlled the time for this transformation. This block copolymer and the water-only method of self-assembly have provided some insights into designing biomimetic systems that can readily adapt to the environmental conditions.

UV-Cross-Linked Polymer Nanostructures with Preserved Asymmetry and Surface Functionality.

Polymer nanostructures can be designed with tailored properties and functions by varying their shape, chemical compositions, and surface functionality. The poor stability of these soft materials in solvent other than water can be overcome by introducing cross-links. However, cross-linking complex morphologies remains a challenge. Here, by using the temperature-directed morphology transformation method, we show that the symmetric (nanoworm) and asymmetric (tadpole) nanostructure cores can be UV-cross-linked through the coupling of styrene and para-chlorostyrene units found in the core by irradiating at 254 nm for up to 5 h. Once cross-linked, these nanostructures maintain their structure in organic solvent, further allowing us to couple on a water-insoluble pro-fluorescent probe with high efficiency.

Biodistribution of PNIPAM-Coated Nanostructures Synthesized by the TDMT Method.

Targeting the spleen with nanoparticles could increase the efficacy of vaccines and cancer immunotherapy, and have the potential to treat intracellular infections including leishmaniasis, trypanosome, splenic TB, AIDS, malaria, and hematological disorders. Although, nanoparticle capture in both the liver and spleen has been well documented, there are only a few examples of specific capture in the spleen alone. It is proposed that the larger the nanoparticle size (>400 nm) the greater the specificity and capture within the spleen. Here, we synthesized five nanostructures with different shapes (ranging from spheres, worms, rods, nanorattles, and toroids) and poly( N-isopropylacrylamide), PNIPAM, surface coating using the temperature-directed morphology transformation (TDMT) method. Globular PNIPAM (i.e., water insoluble) surface coatings have been shown to significantly increase cell uptake and enhanced enzyme activity. We incorporated a globular component of PNIPAM on the nanostructure surface and examined the in vivo biodistribution of these nanostructures and accumulation in various tissues and organs in a mouse model. The in vivo biodistribution as a function of time was influenced by the shape and PNIPAM surface composition, in which organ capture and retention was the highest in the spleen. The rods (∼150 nm in length and 15 nm in width) showed the highest capture and retention of greater than 35% to the initial injection amount compared to all other nanostructures. It was found that the rods specifically targeted the cells in the red pulp region of the spleen due to the shape and PNIPAM coating of the rod. This remarkable accumulation and selectively into the spleen represents new nanoparticle design parameters to develop new splenotropic effects for vaccines and other therapeutics.

Uniform Symmetric and Asymmetric Polymer Nanostructures via Directed Chain Organization.

Polymer nanostructures can be designed with specific properties and functions, such as controlled shape, size, chemical composition, and adaptive ability to change shape or size in response to environmental cues. Precise control to organize polymer chains into uniform nonspherical symmetric and asymmetric nanostructures and at scale remains a synthetic challenge. Here, by using the temperature-directed morphology transformation (TDMT) method we show through a systematic organization of polymer chains the synthesis of well-defined asymmetric (i.e., tadpole) and symmetric (i.e., worm) nanostructures in water at high polymer concentrations. This method further allowed the production of tadpoles with controlled and uniform tail lengths, ranging from 200 to 800 nm. The organization of chains could be driven by environmental conditions to produce adaptive nanostructure systems.

Temperature-Directed Assembly of Stacked Toroidal Nanorattles.

Here, we have developed a new methodology to obtain a pure population of well-defined and new kinetically trapped structures directly in water, inaccessible by other self-assembly techniques. We have exemplified this method through the synthesis of stacked toroidal micelles trapped into a nanorattle with multiple and orthogonal surface chemical functionality. These unique polymer nanorattles result from a water-surrounded inner core (or yolk) of stacked toroidal micelles encapsulated by a shell of stacked toroids. The nanorattles were monodispersed and could be freeze-dried and rehydrated without a change in the nanorattle structure. Confirmation of the kinetically trapped nanorattle structure was through the release of the individual stacked toroids using a plasticizer. Our approach provides a strategy for the synthesis of unique nanostructures that have the potential to be coupled with biological molecules and probes capable of performing multiple tasks and functions.

Temperature-Directed Self-Assembly: from Tadpole to Multi-Arm Polymer Nanostructures Directly in Water.

Driving amphiphilic block copolymers to self-assemble into asymmetric and equilibrium nanostructures remains a challenge. Here, we use the temperature-directed morphology transformation (TDMT) method to tailor the self-assembly of block copolymers into asymmetric nanoparticles with either a single (i.e., tadpole) or multi-arm geometry directly in water and at scale (>10 wt % of polymer). These nanostructures were close to or at their equilibrium morphology and not a transient kinetically trapped structure since they did not change with the addition of high amounts of plasticizer, could be freeze-dried and rehydrated without any structural rearrangement.

Temperature-Directed Self-Assembly of Multifunctional Polymeric Tadpoles.

Multicompartment tadpole nano-objects are a rare and intriguing class of structures with potential in a wide range of applications. Here, we demonstrate the synthesis of chemically multifunctional polymer tadpoles made at high weight fractions of polymer (>10 wt %). The tadpoles are synthesized using two different thermoresponsive MacroCTAs with either alkyne or pyridyldisulfide end-groups, allowing chemical functionality in the head, tail, or both. Water-soluble molecules or polymers were coupled to either the head, tail or both without a change in tadpole configuration. In addition, the tadpoles can be dried, rehydrated, and stored in water for 5 months without a change in shape. This method represents a new and an important synthetic development in the design of nano-objects.

Multifunctional nanoworms and nanorods through a one-step aqueous dispersion polymerization.

Producing synthetic soft worm and rod structures with multiple chemical functionalities on the surface would provide potential utility in drug delivery, nanoreactors, tissue engineering, diagnostics, rheology modifiers, enzyme mimics, and many other applications. Here, we have synthesized multifunctional worms and rods directly in water using a one-step reversible addition-fragmentation chain transfer (RAFT)-mediated dispersion polymerization at high weight fractions of polymer (>10 wt %). The chain-end functionalities included alkyne, pyridyl disulfide, dopamine, ß-thiolactone, and biotin groups. These groups could further be converted or coupled with biomolecules or polymers. We further demonstrated a nanorod colorimetric system with good control over the attachment of fluorescent probes.