Phases of multielement nanoparticles: Thermodynamically stable metal nanoparticles composed of multiple elements could, in principle, exhibit several different phases that form multiple interfaces. Chen et al. explored the structure and composition of palladium-tin alloy nanoparticles formed with up to five other elements after high-temperature annealing. Triphase nanoparticles possessed two or three interface architectures, and tetraphase nanoparticles exhibited up to six interfaces. Theoretical and experimental studies revealed how the balance between surface and interfacial energies influences the observed phases and interface structure. Science , this issue p. 959

Significance: Discovering new materials is traditionally a slow process, as the materials genome encompasses a massive parameter space, particularly on the nanoscale where synthesis methods are less universal. To overcome this challenge, a cantilever-free lithography method has been used to deposit millions of discrete nanoreactors on a substrate, which can be transformed into millions of nanoparticles spatially encoded in terms of composition and size. These compositions were screened for their ability to catalytically grow carbon nanotubes, and a composition (Au ₃ Cu) was identified as optimum for this application. More generally, this combinatorial method of synthesizing nanoparticle megalibraries offers researchers a platform for identifying structures with desired properties at a rate not previously possible.

A one-pot synthesis of micellar spherical nucleic acid (SNA) nanostructures using Pluronic F127 as a thermoresponsive template is reported. These novel constructs are synthesized in a chemically straightforward process that involves intercalation of the lipid tails of DNA amphiphiles (CpG motifs for TLR-9 stimulation) into the hydrophobic regions of Pluronic F127 micelles, followed by chemical cross-linking and subsequent removal of non-cross-linked structures. The dense nucleic acid shell of the resulting cross-linked micellar SNA enhances their stability in physiological media and facilitates their rapid cellular internalization, making them effective TLR-9 immunomodulatory agents. These constructs underscore the potential of SNAs in regulating immune response and address the relative lack of stability of noncovalent constructs.

Spherical nucleic acids (SNAs) are nanomaterials typically consisting of a nanoparticle core and a functional, dense, and highly oriented oligonucleotide shell with unusual biological properties that make them appealing for many applications, including sequence-specific gene silencing, mRNA quantification, and immunostimulation. When placed in biological fluids, SNAs readily interact with serum proteins, leading to the formation of ill-defined protein coronae on the surface, which can influence the targeting capabilities of the conjugate. In this work, SNAs were designed and synthesized with functional proteins, such as antibodies and serum albumin, deliberately adsorbed onto their surfaces. These particles exhibit increased resistance to protease degradation compared with native SNAs but still remain functional, as they can engage in hybridization with complementary oligonucleotides. SNAs with adsorbed targeting antibodies exhibit improved cellular selectivity within mixed cell populations. Similarly, SNAs coated with the dysopsonizing protein serum albumin show reduced macrophage uptake, providing a strategy for tailoring selective SNA delivery. Importantly, the protein coronae remain stable on the SNAs in human serum, exhibiting a less than 45% loss of protein through exchange after 12 h at 37 °C. Taken together, these results show that protein–SNA complexes and the method used to prepare them provide a new avenue for enhancing SNA stability, targeting, and biodistribution.