Urchin-like CoP3/Cu3P heterostructured nanorods supported on a 3D porous copper foam for high-performance non-enzymatic electrochemical dopamine sensors.

In this study, we developed a high-performance non-enzymatic electrochemical sensor based on urchin-like CoP3/Cu3P heterostructured nanorods supported on a three-dimensional porous copper foam, namely, CoP3/Cu3P NRs/CF, for the detection of dopamine. Benefiting from the promising intrinsic catalytic activities of CoP3 and Cu3P, urchin-like microsphere structures, and a large electrochemically active surface area for exposing numerous accessible catalytic active sites, the proposed CoP3/Cu3P NRs/CF shows extraordinary electrochemical response towards the electrocatalytic oxidation of dopamine. As a result, the CoP3/Cu3P NRs/CF sensing electrode has a broad detection window (from 0.2 to 2000 µM), low detection limit (0.51 µM), high electrochemical sensitivity (0.0105 mA µM-1 cm-2), excellent selectivity towards dopamine in the coexistence of some interfering species, and good stability for dopamine determination. More importantly, the CoP3/Cu3P NRs/CF catalyst also exhibits excellent catalytic activity, sensitivity, and selectivity for dopamine detection under simulated human body conditions at a physiological pH of 7.25 (0.1 M PBS) at 36.6 °C.

LED dynamic electro-optical responses and light-fidelity-application optimization.

Commercial light-emitting diodes (LEDs) from different manufacturers were studied by means of impedance measurements in the frequency range between 75 kHz and 10 MHz. Electrical characteristics of these LEDs, such as impedance and resistance, were proven to be strongly influenced by the applied frequencies, the bias values, and the alternating-signal amplitudes. Through these measurements, a specific bias value, which later could be of great importance, was pointed out. Coupled with the optical signal-to-noise ratio measurements, this frequency-, bias-, and alternating-signal-amplitude-dependent impedance shows a close correlation between optical and electrical responses of LEDs, which turns out to be useful for visible light communication. Hence, a new and simple method of light-fidelity optimization through impedance measurements is proposed in this article.

Mannosylated STING Agonist Drugamers for Dendritic Cell-Mediated Cancer Immunotherapy.

The Stimulator of Interferon Genes (STING) pathway is a promising target for cancer immunotherapy. Despite recent advances, therapies targeting the STING pathway are often limited by routes of administration, suboptimal STING activation, or off-target toxicity. Here, we report a dendritic cell (DC)-targeted polymeric prodrug platform (polySTING) that is designed to optimize intracellular delivery of a diamidobenzimidazole (diABZI) small-molecule STING agonist while minimizing off-target toxicity after parenteral administration. PolySTING incorporates mannose targeting ligands as a comonomer, which facilitates its uptake in CD206+/mannose receptor+ professional antigen-presenting cells (APCs) in the tumor microenvironment (TME). The STING agonist is conjugated through a cathepsin B-cleavable valine-alanine (VA) linker for selective intracellular drug release after receptor-mediated endocytosis. When administered intravenously in tumor-bearing mice, polySTING selectively targeted CD206+/mannose receptor+ APCs in the TME, resulting in increased cross-presenting CD8+ DCs, infiltrating CD8+ T cells in the TME as well as maturation across multiple DC subtypes in the tumor-draining lymph node (TDLN). Systemic administration of polySTING slowed tumor growth in a B16-F10 murine melanoma model as well as a 4T1 murine breast cancer model with an acceptable safety profile. Thus, we demonstrate that polySTING delivers STING agonists to professional APCs after systemic administration, generating efficacious DC-driven antitumor immunity with minimal side effects. This new polymeric prodrug platform may offer new opportunities for combining efficient targeted STING agonist delivery with other selective tumor therapeutic strategies.

Correction to "Mannosylated STING Agonist Drugamers for Dendritic Cell-Mediated Cancer Immunotherapy".

[This corrects the article DOI: 10.1021/acscentsci.3c01310.].

A mannosylated polymer with endosomal release properties for peptide antigen delivery.

Peptide cancer vaccines have had limited clinical success despite their safety, characterization and production advantages. We hypothesize that the poor immunogenicity of peptides can be surmounted by delivery vehicles that overcome the systemic, cellular and intracellular drug delivery barriers faced by peptides. Here, we introduce Man-VIPER, a self-assembling (40-50 nm micelles), pH-sensitive, mannosylated polymeric peptide delivery platform that targets dendritic cells in the lymph nodes, encapsulates peptide antigens at physiological pH, and facilitates endosomal release of antigens at acidic endosomal pH through a conjugated membranolytic peptide melittin. We used d-melittin to improve the safety profile of the formulation without compromising the lytic properties. We evaluated polymers with both releasable (Man-VIPER-R) or non-releasable (Man-VIPER-NR) d-melittin. Both Man-VIPER polymers exhibited superior endosomolysis and antigen cross-presentation compared to non-membranolytic d-melittin-free analogues (Man-AP) in vitro. In vivo, Man-VIPER polymers demonstrated an adjuvanting effect, induced the proliferation of antigen-specific cytotoxic T cells and helper T cells compared to free peptides and Man-AP. Remarkably, antigen delivery with Man-VIPER-NR generated significantly more antigen-specific cytotoxic T cells than Man-VIPER-R in vivo. As our candidate for a therapeutic vaccine, Man-VIPER-NR exerted superior efficacy in a B16F10-OVA tumor model. These results highlight Man-VIPER-NR as a safe and powerful peptide cancer vaccine platform for cancer immunotherapy.

Well-Defined Mannosylated Polymer for Peptide Vaccine Delivery with Enhanced Antitumor Immunity.

Peptide-based cancer vaccines offer production and safety advantages but have had limited clinical success due to their intrinsic instability, rapid clearance, and low cellular uptake. Nanoparticle-based delivery vehicles can improve the in vivo stability and cellular uptake of peptide antigens. Here, a well-defined, self-assembling mannosylated polymer is developed for anticancer peptide antigen delivery. The amphiphilic polymer is prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization, and the peptide antigens are conjugated to the pH-sensitive hydrophobic block through the reversible disulfide linkage for selective release after cell entry. The polymer-peptide conjugates self-assemble into sub-100 nm micelles at physiological pH and dissociate at endosomal pH. The mannosylated micellar corona increases the accumulation of vaccine cargoes in the draining inguinal lymph nodes and facilitates nanoparticle uptake by professional antigen presenting cells. In vivo studies demonstrate that the mannosylated micelle formulation improves dendritic cell activation and enhances antigen-specific T cell responses, resulting in higher antitumor immunity in tumor-bearing mice compared to free peptide antigen. The mannosylated polymer is therefore a simple and promising platform for the delivery of peptide cancer vaccines.

Amphiphilic Polyelectrolyte Graft Copolymers Enhance the Activity of Cyclic Dinucleotide STING Agonists.

Cyclic dinucleotide (CDN) agonists of stimulator of interferon genes (STING) hold great therapeutic potential, but their activity is hindered by poor drug-like properties that restrict cytosolic bioavailability. Here, this challenge is addressed through the synthesis and evaluation of a novel series of PEGMA-co-DEAEMA-co-BMA copolymers with pH-responsive, membrane-destabilizing activity to enhance intracellular delivery of the CDN, cGAMP. Copolymers are synthesized with PEGMA of two different molecular weights (300 and 950 Da) and over a range of PEG mass fraction and polymer molecular weight, and relationships between copolymer structure, self-assembly, endosomal escape, and cGAMP activity are elucidated. A subset of polymers that self-assembled into 50-800 nm nanoparticles is identified, which can be loaded with cGAMP via a simple mixing strategy, resulting in significantly enhanced immunostimulatory activity. Increased cGAMP activity is found to be highly correlated with the capacity of carriers to enhance intracellular CDN uptake and to promote endosomal destabilization, findings that establish efficient cytosolic delivery as a criterion for CDN carriers. Additionally, it is demonstrated that a lead CDN carrier formulation can enhance STING activation in vivo in a model of intratumoral immunotherapy. Collectively, these investigations demonstrate the utility of PEGMA-co-DEAEMA-co-BMA copolymers as carriers for CDNs and potentially other cytosolically-acting drug cargo.

Hierarchical Manganese-Nickel Sulfide Nanosheet Arrays as an Advanced Electrode for All-Solid-State Asymmetric Supercapacitors.

In this work, hierarchical manganese-nickel sulfide nanosheet arrays (Mn-Ni-S NAs) were designed through a cost-effective hydrothermal method, followed by an ion-exchange technique. Among the various electrode samples prepared, Mn-Ni-S NAs with a Mn/Ni feeding ratio of 1:2 (denoted Mn-Ni-S NAs (1:2)) were found to possess outstanding electrochemical properties, including a superb areal capacity of 0.687 mAh cm-2 (286.3 mAh g-1 specific capacity) and a splendid cycling stability. Furthermore, Mn-Ni-S NAs (1:2) can be coupled with iron oxide embedded in reduced graphene oxides (Fe2O3@rGO) to assemble all-solid-state asymmetric supercapacitor devices. The resultant device demonstrated superior volumetric capacity and a superb energy density of 76.6 W h kg-1 with a prominent cycling stability. The current synthesis protocol provides a meritorious reference for the synthesis of other kinds of transition-metal sulfide electrode materials for energy storage applications.