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Decorative journal cover. Layered nanoparticles functionalized with protease-responsive peptide biomarkers and loaded with siRNA enable non-invasive urinary diagnostics in mouse models of three different cancer types with simultaneous gene silencing in adjacent and metastatic mouse models of ovarian cancer. P. T. Hammond et al. describe in their Research Article on page 2798 a modular nanotheranostics platform that can both disrupt and characterize tumors, allowing simultaneous treatment and monitoring of the disease.

Decorative journal cover. Immune status and responses are often determined by analyzing circulating cells isolated from the blood. However, many immune processes and diseases depend on tissue-resident immune cells acting in target organs, which would not be reflected in peripheral immune cells. To sample these tissue-resident cells, Mandal et al. designed a microneedle array that can be applied to the skin. These microneedles can be loaded with adjuvants and antigens of interest to draw in responding immune cells. The microneedles are noninvasive and can be used to follow immune responses over time; similar sampling could be done in the future for other tissues. Tools such as these microneedles can help scientists gain a more accurate understanding of immune responses.

Decorative journal cover. The development of stable skeletal joint prostheses - con-formal, nanoscale electrostatic coatings capable of de novo bone regeneration - is reported by P. T. Hammond and co-workers. These coatings contain a combination of hydroxyapatite and bone growth factor, components which are present in and which regulate the structure of the bone. Osteoblast cells adhere to these coatings and lay down new bone on and around the implant for stable bonding with the surrounding bone tissue.

Decorative journal cover. Advanced staged high-grade serous ovarian cancer (HGSOC) is the leading cause of gynecological cancer death in the developed world. In this study, we address the challenge of resistance to platinum-based therapy by developing a targeted delivery approach. Novel electrostatic layer-by-layer (LbL) liposomal nanoparticles (NPs) with a terminal hyaluronic acid layer that facilitates CD44 receptor targeting are designed for selective targeting of HGSOC cells; the liposomes can be formulated to contain both cisplatin and the PARPi drug within the liposomal core and bilayer. The NPs exhibited prolonged blood circulation half-life, mechanistic staged drug release and targeted codelivery of the therapeutic agents to HGSOC cells. Moreover, compared to the free drugs, the NPs resulted in significantly reduced tumor metastasis, extended survival, and moderated systemic toxicity.

Decorative journal cover. Uncontrolled bleeding from traumatic wounds is a major factor in deaths resulting from military conflict, accidents, disasters and crime. Self-assembling peptide nanofibers have shown superior hemostatic activity, and herein, we elucidate their mechanism by visualizing the formation of nanofiber-based clots that aggregate blood components with a similar morphology to fibrin-based clots.

Decorative journal image. Morton et al. developed a dual-drug, time-delayed nanoparticle delivery system for treating cancer. The nanoparticles contained two drugs (one in the membrane and one in the center) and were coated to target the nanoparticles to cancer cells. Cancer cells took up the nanoparticles. The first drug quickly escaped the nanoparticle, sensitizing the cells to the second drug, which escaped more slowly. In mice, tumors from cells that respond to the first drug were reduced when the mice were treated with the dual-drug nanoparticles, but the tumors continued to grow in mice receiving only single-drug therapy. This time-delayed, nanoparticle-mediated drug delivery may avoid the resistance that cancer cells develop to chemotherapy.

Decorative journal cover. The encapsulation and delivery of short interfering RNA (siRNA) has been realized using lipid nanoparticles, cationic complexes, inorganic nanoparticles, RNA nanoparticles and dendrimers. Still, the instability of RNA and the relatively ineffectual encapsulation process of siRNA remain critical issues towards the clinical translation of RNA as a therapeutic. Lee et al. report the synthesis of a delivery vehicle that combines carrier and cargo: RNA interference (RNAi) polymers that self-assemble into nanoscale pleated sheets of hairpin RNA, which in turn form sponge-like microspheres. The RNAi-microsponges consist entirely of cleavable RNA strands, and are processed by the cell’s RNA machinery to convert the stable hairpin RNA to siRNA only after cellular uptake, thus inherently providing protection for siRNA during delivery and transport to the cytoplasm. More than half a million copies of siRNA can be delivered to a cell with the uptake of a single RNAi-microsponge. The approach could lead to novel therapeutic routes for siRNA delivery.

Decorative journal cover. With an aging population comes more and more surgical implants to stabilize broken hips and replace worn-down joints. Despite their widespread application, these biomedical implants can loosen by not integrating fully with the host tissue; this requires revision surgery and increases patient morbidity. In response, Shah and colleagues designed a series of biochemical coatings that can be applied to both polymer (PEEK) and metal (titanium) surfaces to help implants develop a strong interface with existing bone.

ACS Nano cover featuring work on nanocoated implants to enhance bone regeneration.

Clinical cancer research journal cover highlighting layer-by-layer nanoparticle delivery of synergistic MAPK and PI3K inhibitors.

Advanced materials journal cover showing nanocomposites templated on bacteriophage.

Back cover of the journal advanced materials, highlighting the ability to layer polyelectrolytes on bacteriophage surfaces.

Science

Science

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