Evolution of Dip-Pen Nanolithography (DPN): From Molecular Patterning to Materials Discovery.

Dip-pen nanolithography (DPN) is a nanofabrication technique that can be used to directly write molecular patterns on substrates with high resolution and registration. Over the past two decades, DPN has evolved in its ability to transport molecular and material "inks" (e.g., alkanethiols, biological molecules like DNA, viruses, and proteins, polymers, and nanoparticles) to many surfaces in a high-throughput fashion, enabling the synthesis and study of complex chemical and biological structures. In addition, DPN has laid the foundation for a series of related scanning probe methodologies, for example, polymer pen lithography (PPL), scanning probe block copolymer lithography (SPBCL), and beam-pen lithography (BPL), which do not rely on cantilever tips. Structures prepared with these methodologies have been used to understand the consequences of miniaturization and open a door to new capabilities in catalysis, optics, biomedicine, and chemical synthesis, where, in sum, a process originally intended to compete with tools used by the semiconductor industry for rapid prototyping has transcended that application to advanced materials discovery. This review outlines the major DPN advances, the subsequent methods based on the technique, and the opportunities for future fundamental and technological exploration. Most importantly, it commemorates the 20th anniversary of the discovery of DPN.

Spherical Nucleic Acids: Integrating Nanotechnology Concepts into General Chemistry Curricula.

Nanoscience and technology research offer exciting avenues to modernize undergraduate-level General Chemistry curricula. In particular, spherical nucleic acid (SNA) nanoconjugates, which behave as "programmable atom equivalents" (PAEs) in the context of colloidal crystals, are one system that one can use to reinforce foundational concepts in chemistry including matter and atoms, the Periodic Table, Lewis dot structures and the octet rule, valency and valence-shell electron-pair repulsion (VSEPR) theory, and Pauling's rules, ultimately leading to enriching discussions centered on materials chemistry and biochemistry with key implications in medicine, optics, catalysis, and other areas. These lessons connect historical and modern concepts in chemistry, relate course content to current professional and popular science topics, inspire critical and creative thinking, and spur some students to continue their science, technology, engineering, and mathematics (STEM) education and attain careers in STEM fields. Ultimately, and perhaps most importantly, these lessons may expand the pool of young students interested in chemistry by making connections to a broader group of contemporary concepts and technologies that impact their lives and enhance their view of the field. Herein, a way of teaching aspects of General Chemistry in the context of modern nanoscience concepts is introduced to instructors and curricula developers at research institutions, primarily undergraduate institutions, and community colleges worldwide.

Direct Observation of Plasmon-Induced Interfacial Charge Separation in Metal/Semiconductor Hybrid Nanostructures by Measuring Surface Potentials.

Plasmon-induced interfacial charge separation (PICS) is one of the key processes responsible for the improved conversion efficiencies of energy-harvesting devices that incorporate metal nanostructures. In this Letter, we reveal a mechanism of PICS by visualizing (with nanometer-scale resolution) and characterizing plasmon-exciton coupling between p-type poly(pyrrole) (PPy) nanowires (NWs) and Ag nanoparticles (NPs) using light-irradiated Kelvin probe force microscopy (KPFM). Under blue-light irradiation, the Ag NPs are expected to donate electrons to the PPy NWs via a hot electron injection process. However, in this Letter, we observe that under blue-light irradiation the plasmonically and excitonically excited electrons in the semiconductor back-transfer to the metal. The PICS in this system can be explained by comparing it with a similar one where Au NPs are attached to n-type ZnO NWs; we observed a net electron transfer from the Au NPs to the ZnO NWs (an upward band bending is formed at the interface of the two materials, presumably obstructing electron back-transfer). Indeed, energy band matching between the metal and the semiconductor components of hybrid nanostructures influences PICS pathways. These experimental findings and our proposed mechanism consistently explain the PICS occurring in the PPy NW-Ag NP system with important implications on explaining their cooperative optoelectronic activities.

Molecular Transport Junctions Created By Self-Contacting Gapped Nanowires.

Molecular transport junctions (MTJs) are important components in molecular electronic devices. However, the synthesis of MTJs remains a significant challenge, as the dimensions of the junction must be tailored for each experiment, based on the molecular lengths. A novel methodology is reported for forming MTJs, taking advantage of capillary and van der Waals forces.

Nanoflares as probes for cancer diagnostics.

Patients whose cancer is detected early are much more likely to have a positive prognosis and outcome. Nanoflares hold promise as a practical diagnostic platform for the early detection of cancer markers in living cells. These probes are based on spherical nucleic acid (SNAs) and are typically composed of gold nanoparticle cores and densely packed and highly oriented oligonucleotide shells; these sequences are complementary to specific mRNA targets and are hybridized to fluorophore-labeled reporter strands. Nanoflares take advantage of the highly efficient fluorescence quenching properties of gold, the rapid cellular uptake of SNAs that occurs without the use of transfection agents, and the enzymatic stability of such constructs to report a highly sensitive and specific signal in the presence of intracellular target mRNA. In this chapter, we will focus on the synthesis, characterization, and diagnostic applications of nanoflares as they relate to cancer markers.

Therapeutic applications of spherical nucleic acids.

Spherical nucleic acids (SNAs) represent an emerging class of nanoparticle-based therapeutics. SNAs consist of densely functionalized and highly oriented oligonucleotides on the surface of a nanoparticle which can either be inorganic (such as gold or platinum) or hollow (such as liposomal or silica-based). The spherical architecture of the oligonucleotide shell confers unique advantages over traditional nucleic acid delivery methods, including entry into nearly all cells independent of transfection agents and resistance to nuclease degradation. Furthermore, SNAs can penetrate biological barriers, including the blood-brain and blood-tumor barriers as well as the epidermis, and have demonstrated efficacy in several murine disease models in the absence of significant adverse side effects. In this chapter, we will focus on the applications of SNAs in cancer therapy as well as discuss multimodal SNAs for drug delivery and imaging.

Inspired Beyond Nature: Three Decades of Spherical Nucleic Acids and Colloidal Crystal Engineering with DNA.

The conception, synthesis, and invention of a nanostructure, now known as the spherical nucleic acid, or SNA, in 1996 marked the advent of a new field of chemistry. Over the past three decades, the SNA and its analogous anisotropic equivalents have provided an avenue for us to think about some of the most fundamental concepts in chemistry in new ways and led to technologies that are significantly impacting fields from medicine to materials science. A prime example is colloidal crystal engineering with DNA, the framework for using SNAs and related structures to synthesize programmable matter. Herein, we document the evolution of this framework, which was initially inspired by nature, and describe how it now allows researchers to chart paths to move beyond it, as programmable matter with real-world significance is envisioned and created.

Programmable Matter: The Nanoparticle Atom and DNA Bond.

Colloidal crystal engineering with DNA has led to significant advances in bottom-up materials synthesis and a new way of thinking about fundamental concepts in chemistry. Here, programmable atom equivalents (PAEs), comprised of nanoparticles (the "atoms") functionalized with DNA (the "bonding elements"), are assembled through DNA hybridization into crystalline lattices. Unlike atomic systems, the "atom" (e.g., the nanoparticle shape, size, and composition) and the "bond" (e.g., the DNA length and sequence) can be tuned independently, yielding designer materials with unique catalytic, optical, and biological properties. In this review, nearly three decades of work that have contributed to the evolution of this class of programmable matter is chronicled, starting from the earliest examples based on gold-core PAEs, and then delineating how advances in synthetic capabilities, DNA design, and fundamental understanding of PAE-PAE interactions have led to new classes of functional materials that, in several cases, have no natural equivalent.

Rational Vaccinology: Harnessing Nanoscale Chemical Design for Cancer Immunotherapy.

Cancer immunotherapy is a powerful treatment strategy that mobilizes the immune system to fight disease. Cancer vaccination is one form of cancer immunotherapy, where spatiotemporal control of the delivery of tumor-specific antigens, adjuvants, and/or cytokines has been key to successfully activating the immune system. Nanoscale materials that take advantage of chemistry to control the nanoscale structural arrangement, composition, and release of immunostimulatory components have shown significant promise in this regard. In this Outlook, we examine how the nanoscale structure, chemistry, and composition of immunostimulatory compounds can be modulated to maximize immune response and mitigate off-target effects, focusing on spherical nucleic acids as a model system. Furthermore, we emphasize how chemistry and materials science are driving the rational design and development of next-generation cancer vaccines. Finally, we identify gaps in the field that should be addressed moving forward and outline future directions to galvanize researchers from multiple disciplines to help realize the full potential of this form of cancer immunotherapy through chemistry and rational vaccinology.

Accelerating the Translation of Nanomaterials in Biomedicine.

Due to their size and tailorable physicochemical properties, nanomaterials are an emerging class of structures utilized in biomedical applications. There are now many prominent examples of nanomaterials being used to improve human health, in areas ranging from imaging and diagnostics to therapeutics and regenerative medicine. An overview of these examples reveals several common areas of synergy and future challenges. This Nano Focus discusses the current status and future potential of promising nanomaterials and their translation from the laboratory to the clinic, by highlighting a handful of successful examples.

CO2 Preactivation in Photoinduced Reduction via Surface Functionalization of TiO2 Nanoparticles.

Salicylate and salicylic acid derivatives act as electron donors via charge-transfer complexes when adsorbed on semiconducting surfaces. When photoexcited, charge is injected into the conduction band directly from their highest occupied molecular orbital (HOMO) without needing mediation by the lowest unoccupied molecular orbital (LUMO). In this study, we successfully induce the chemical participation of carbon dioxide in a charge transfer state using 3-aminosalicylic acid (3ASA). We determine the geometry of CO2 using a combination of ultraviolet-visible spectroscopy (UV-vis), surface enhanced Raman scattering (SERS), (13)C NMR, and electron paramagnetic resonance (EPR). We find CO2 binds on Ti sites in a carbonate form and discern via EPR a surface Ti-centered radical in the vicinity of CO2, suggesting successful charge transfer from the sensitizer to the neighboring site of CO2. This study opens the possibility of analyzing the structural and electronic properties of the anchoring sites for CO2 on semiconducting surfaces and proposes a set of tools and experiments to do so.