Current approaches to nanoscale therapeutic delivery rely on the attachment of a drug of interest to a nanomaterial scaffold that is capable of releasing the drug selectively in a tumor environment. One class of nanocarriers receiving significant attention is protein nanomaterials, which are biodegradable and homogeneous in morphology and can be equipped with multiple functional handles for drug attachment. Although most protein-based nanocarriers are spherical in morphology, recent research has revealed that nonspherical nanomaterials may have favorable tumor uptake in comparison to their spherical counterparts. It is therefore important to expand the number of nonspherical protein-based nanocarriers that are available. Herein, we report the development of a self-assembling nanoscale disk derived from a double arginine mutant of recombinantly expressed tobacco mosaic virus coat protein (RR-TMV). RR-TMV disks display highly stable double-disk assembly states. These RR-TMV disks were functionalized with the chemotherapy drug doxorubicin (DOX) and further modified with polyethylene glycol (PEG) for improved solubility. RR-TMV displayed cytotoxic properties similar to those of DOX alone when incubated with U87MG glioblastoma cells, but unmodified RR-TMV did not cause any cytotoxicity. The RR-TMV disk assembly represents a promising protein-based nanomaterial for applications in drug delivery.
We have developed a method for integrating the self-assembling tobacco mosaic virus capsid into hydrophobic solvents and hydrophobic polymers. The capsid was modified at tyrosine residues to display an array of linear poly(ethylene glycol) chains, allowing it to be transferred into chloroform. In a subsequent step, the capsids could be transferred to a variety of hydrophobic solvents, including benzyl alcohol, o-dichlorobenzene, and diglyme. The thermal stability of the material against denaturation increased from 70 °C in water to at least 160 °C in hydrophobic solvents. With a view toward material fabrication, the polymer-coated TMV rods were also incorporated into solid polystyrene and thermally cast at 110 °C. Overall, this process significantly expands the range of processing conditions for TMV-based materials, with the goal of incorporating these templated nanoscale systems into conductive polymer matrices.
In the search for vacuum solutions, with or without a cosmological constant, Λ, of the Einstein field equations of Petrov type N with twisting principal null directions, the CR structures to describe the parameter space for a congruence of such null vectors provide a very useful tool. Work of Hill, Lewandowski and Nurowski has given a good foundation for this, reducing the field equations to a set of differential equations for two functions, one real and one complex, of three variables. Under the assumption of the existence of one Killing vector, the (infinite-dimensional) classical symmetries of those equations are determined and group-invariant solutions are considered. This results in a single ODE of the third order which may easily be reduced to one of the second order. A one-parameter class of power series solutions, g(w), of this second-order equation is realized, holomorphic in a neighborhood of the origin and behaving asymptotically as a simple quadratic function plus lower order terms for large values of w, which constitutes new solutions of the twisting type N problem. The solution found by Leroy, and also by Nurowski, is shown to be a special case in this class. Cartan’s method for determining equivalence of CR manifolds is used to show that this class is indeed much more general. In addition, for a special choice of a parameter, this ODE may be integrated once to provide a first-order Abel equation. It can also determine new solutions to the field equations, although no general solution has yet been found for it.
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