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.

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.

Driving amphiphilic block copolymers to selfassemble 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.

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.

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, crosslinking 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-crosslinked 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.