Endosomal Organization of CpG Constructs Correlates with Enhanced Immune Activation.

This Letter describes how the endosomal organization of immunostimulatory nanoconstructs can tune the in vitro activation of macrophages. Nanoconstructs composed of gold nanoparticles conjugated with unmethylated cytosine-phosphate-guanine (CpG) oligonucleotides have distinct endosomal distributions depending on the surface curvature. Mixed-curvature constructs produce a relatively high percentage of hollow endosomes, where constructs accumulated primarily along the interior edges. These constructs achieved a higher level of toll-like receptor (TLR) 9 activation along with the enhanced secretion of proinflammatory cytokines and chemokines compared to constant-curvature constructs that aggregated mostly in the center of the endosomes. Our results underscore the importance of intraendosomal interactions in regulating immune responses and targeted delivery.

Enhanced Photodetection Properties of Tellurium@Selenium Roll-to-Roll Nanotube Heterojunctions.

Non-layered tellurium (Te) is a promising material for applications in transistor and optoelectronic devices for its advantages in excellent intrinsic electronic and optoelectronic properties. However, the poor photodetection performance and relatively uncertain stability of tellurene under ambient conditions greatly limit the practical applications. In order to improve the performance of tellurene-based materials, Te@Se roll-to-roll nanotubes with different selenium (Se) contents synthesized by epitaxial growth of Se on Te nanotubes are, for the first time, employed to fabricate working electrodes for photoelectrochemical (PEC)-type broadband photodetection. They exhibit not only a preferably enhanced capacity for self-powered broadband photodetection but also significantly improved photocurrent density and stability in various aqueous environments (HCl, NaCl, and KOH solutions), compared to tellurene-based photodetectors. It is anticipated that the present work can open up new possibilities for high-performance tellurene-based optoelectronic devices.

Synergistic Immunostimulation through the Dual Activation of Toll-like Receptor 3/9 with Spherical Nucleic Acids.

Toll-like receptors (TLRs) are a family of proteins that modulate the innate immune system and control the initiation of downstream immune responses. Spherical nucleic acids (SNAs) designed to stimulate single members of the TLR family (e.g., TLR7 or TLR9) have shown utility in cancer immunotherapy. We hypothesized that SNAs synthesized with multiple TLR agonists would enable the simultaneous activation of multiple TLR pathways for maximally synergistic immune activation. Here, we describe the synthesis of SNAs that incorporate both a TLR3 agonist (polyinosinic:polycytidylic acid, poly(I:C)) and TLR9 agonist (CpG oligonucleotide) on the same liposomal scaffold. In this design, CpG comprises the SNA oligonucleotide shell, and poly(I:C) is encapsulated in the liposome core. These dual-TLR activating SNAs efficiently codeliver high quantities of both agonists to the same target cell, yielding enhanced immunostimulation in various murine and human antigen-presenting cells (APCs). Moreover, codelivery of TLR agonists using the SNA both synchronizes and prolongs the duration of costimulatory molecule and major histocompatibility complex class II expression in APCs, which has been shown to be important for efficient downstream immune responses. Taken together, this SNA design provides a strategy for potently activating immune cells and increasing the efficiency of their activation, which likely will inform the preparation of nanomaterials for highly potent immunotherapies.

Sequence Multiplicity within Spherical Nucleic Acids.

The synthesis and evaluation of spherical nucleic acids (SNAs) incorporating two physically and chemically distinct classes of oligonucleotides (ODNs) at programmed ratios are described. These SNAs are single entity agents that enter the same target cell at defined stoichiometries, and as such allow one to control important cell signaling and regulatory processes. To study the effect of sequence multiplicity within such structures, we synthesized SNAs consisting of a mixture of class A CpG and class B CpG, immunostimulatory ODNs that activate two different toll-like receptor 9 signaling pathways, each in a sequence-specific fashion. These dual-CpG SNAs exhibit high cellular uptake and codelivery of the two ODNs, relative to mixtures of the linear ODN counterparts, and remain highly associated inside the cell over time. Furthermore, the dual-CpG SNAs augment dendritic cell maturation, compared to the same amounts of oligonucleotides delivered in linear or SNA form but not conjugated to one another. Consequently, these structures constitute a platform for designing oligonucleotide-based combination therapeutics with highly tailorable activities.

Two-dimensional beta-lead oxide quantum dots.

In recent years, black-phosphorus-analogue (BPA) two-dimensional (2D) materials have been explored to demonstrate promising optoelectronic performances and distinguished ambient stabilities, holding great promise in practical applications. Here, one new kind of BPA material, orthorhombic ß-PbO quantum dots (QDs), is successfully fabricated by a facile liquid phase exfoliation (LPE) technique. The as-prepared ß-PbO QDs show a homogeneous distribution of the lateral size (3.2 ± 0.9 nm) and thickness (2.5 ± 0.5 nm), corresponding to 4 ± 1 layers. The carrier dynamics of ß-PbO QDs was systematically investigated via a femtosecond resolution transient absorption approach in the visible wavelength regime and it was clarified that two decay components were resolved with a decay time of τ1 = 2.3 ± 0.3 ps and τ2 = 87.9 ± 6.0 ps, respectively, providing important insights into their potential applications in the field of ultrafast optics, nanomechanics and optoelectronics. As a proof-of-concept, ß-PbO QDs were, for the first time to our knowledge, fabricated as a working electrode in a photoelectrochemical (PEC)-typed photodetector that exhibits significantly high photocurrent density and excellent stability under ambient conditions.