Glioblastoma (GBM) is one of the most difficult cancers to effectively treat, in part because of the lack of precision therapies and limited therapeutic access to intracranial tumor sites due to the presence of the blood-brain and blood-tumor barriers. We have developed a precision medicine approach for GBM treatment that involves the use of brain-penetrant RNA interference–based spherical nucleic acids (SNAs), which consist of gold nanoparticle cores covalently conjugated with radially oriented and densely packed small interfering RNA (siRNA) oligonucleotides. On the basis of previous preclinical evaluation, we conducted toxicology and toxicokinetic studies in nonhuman primates and a single-arm, open-label phase 0 first-in-human trial (NCT03020017) to determine safety, pharmacokinetics, intratumoral accumulation and gene-suppressive activity of systemically administered SNAs carrying siRNA specific for the GBM oncogene Bcl2Like12 (Bcl2L12). Patients with recurrent GBM were treated with intravenous administration of siBcl2L12-SNAs (drug moniker: NU-0129), at a dose corresponding to 1/50th of the no-observed-adverse-event level, followed by tumor resection. Safety assessment revealed no grade 4 or 5 treatment–related toxicities. Inductively coupled plasma mass spectrometry, x-ray fluorescence microscopy, and silver staining of resected GBM tissue demonstrated that intravenously administered SNAs reached patient tumors, with gold enrichment observed in the tumor-associated endothelium, macrophages, and tumor cells. NU-0129 uptake into glioma cells correlated with a reduction in tumor-associated Bcl2L12 protein expression, as indicated by comparison of matched primary tumor and NU-0129–treated recurrent tumor. Our results establish SNA nanoconjugates as a potential brain-penetrant precision medicine approach for the systemic treatment of GBM.

We develop a model for the excitation of erbium ions in erbium-doped silicon nanocrystals via coupling from confined excitons generated within the silicon nanoclusters. The model provides a phenomenological picture of the exchange mechanism and allows us to evaluate an effective absorption cross section for erbium of up to 7.3ϫ10 Ϫ17 cm 2 : four orders of magnitude higher than in stoichiometric silica. We address the origin of the 1.6 eV emission band associated with the silicon nanoclusters and determine absorption cross sections and excitonic lifetimes for nanoclusters in silica which are of the order of 1.02ϫ10 Ϫ16 cm 2 and 20-100 s, respectively.

InGaN multiple-quantum-well structures grown by metal–organic chemical-vapor deposition on GaN and capped by p-type GaN are found to contain inverted pyramids of indium-free GaN. High-resolution structural and chemical analyses of these “V-defects” by a number of complementary transmission electron microscopy techniques show that the InGaN quantum wells end abruptly at the V-defect interfaces, which lie on {10–11} planes. Each V-defect has at its center a threading edge dislocation, indicating that the defects are initiated at edge dislocation cores in the presence of indium. The lower temperatures of InGaN/GaN quantum-well growth (790 °C/950 °C) assist the formation of V-pits, which are subsequently filled in during the growth at higher temperature (1045 °C) of the p-type capping layer.

Improving composite battery electrodes requires a delicate control of active materials and electrode formulation. The electrochemically active particles fulfill their role as energy exchange reservoirs through interacting with the surrounding conductive network. We formulate a network evolution model to interpret the regulation and equilibration between electrochemical activity and mechanical damage of these particles. Through statistical analysis of thousands of particles using x-ray phase contrast holotomography in a LiNi 0.8 Mn 0.1 Co 0.1 O 2 -based cathode, we found that the local network heterogeneity results in asynchronous activities in the early cycles, and subsequently the particle assemblies move toward a synchronous behavior. Our study pinpoints the chemomechanical behavior of individual particles and enables better designs of the conductive network to optimize the utility of all the particles during operation.

The ability to precisely arrange molecules or particles on the nanometer scale is an opportunity approached from many experimental perspectives. Molecular self-assembly is particularly promising for "bottom-up" nanofabrication because of its versatility and potential ease to pattern features on the nanometer size scale unavailable with conventional "top-down" (e.g., lithography) methods. Facile control of the size, shape, and spatial distribution of nanoparticles, proteins, and biomolecules creates opportunities with applications in fields ranging from nanoelectronics to biosensing. In a recent review, Kotov et al. described particular interest in one-dimensional nanostructures constructed by the linear assembly of inorganic nanoparticles because of the interparticle electronic, photonic, and energy transfer properties which give rise to potential device applications as well as provide model systems for the fundamental understanding of interparticle nanometer-scale phenomena.[1] Currently, there are a variety of solution-based assembly strategies being explored for the fabrication of linear inorganic nanoparticle assemblies. Most of these solution assembly strategies involve the use of a linear template such as polymers [2] or carbon nanotubes.[3] Biological molecules offer great potential for use in such applications because of the complexity of nanostructures they can inherently form and the ability to design multiple types and numbers of interactions within the same molecule. [4,5] DNA is a widely used template and has been shown by Seeman [6][7][8] and others [9][10][11][12][13] to be useful as a programmable two-dimensional template for the organization of inorganic nanoparticle arrays. Protein-based materials such as collagen, [14] microtubules, [15] amyloid fibrils, [16] viruses, [17][18][19] and de novo designed peptide assemblies [20][21][22][23][24] are a few examples of linear templates used for constructing 1D nanoparticle assemblies. Despite the diversity of templates employed thus far, most attempts, with the exception of DNA, have resulted in linear nanoparticle assemblies without specific control over relative particle placement. In this Communication, we demonstrate the ability of a de novo designed peptide-based template, formed through simple solution-based self-assembly and exhibiting a unique nontwisted, laminated morphology, [25] to produce periodically spaced, parallel, linear nanoparticle arrays. Research in the Pochan and Schneider groups has focused on the design of peptides and the understanding of their selfassembly behavior for biomaterials applications in tissue engineering as well as the current interest in construction of peptide-inorganic hybrid materials for potential nanotechnology applications. [25][26][27][28][29][30] Synthetic peptides can be designed to adopt specific secondary conformations, such as an a-helix or b-sheet, by utilization of specific design motifs. In turn, intermolecular interactions can be utilized to direct the formation of complex, hierarchical assemblies...