A terahertz meta-sensor array for 2D strain mapping.

Large-scale stretchable strain sensor arrays capable of mapping two-dimensional strain distributions have gained interest for applications as wearable devices and relating to the Internet of Things. However, existing strain sensor arrays are usually unable to achieve accurate directional recognition and experience a trade-off between high sensing resolution and large area detection. Here, based on classical Mie resonance, we report a flexible meta-sensor array that can detect the in-plane direction and magnitude of preloaded strains by referencing a dynamically transmitted terahertz (THz) signal. By building a one-to-one correspondence between the intrinsic electrical/magnetic dipole resonance frequency and the horizontal/perpendicular tension level, arbitrary strain information across the meta-sensor array is accurately detected and quantified using a THz scanning setup. Particularly, with a simple preparation process of micro template-assisted assembly, this meta-sensor array offers ultrahigh sensor density (~11.1 cm-2) and has been seamlessly extended to a record-breaking size (110 × 130 mm2), demonstrating its promise in real-life applications.

Tunable C4-Symmetry-Broken Metasurfaces Based on Phase Transition of Vanadium Dioxide (VO2).

Coupling is a ubiquitous phenomenon observed in various systems, which profoundly alters the original oscillation state of resonant systems and leads to the unique optical properties of metasurfaces. In this study, we introduce a terahertz (THz) tunable coupling metasurface characterized by a four-fold rotation (C4) symmetry-breaking structural array achieved through the incorporation of vanadium dioxide (VO2). This disruption of the C4 symmetry results in dynamically controlled electromagnetic interactions and couplings between excitation modes. The coupling between new resonant modes modifies the peak of electromagnetic-induced transparency (EIT) within the C4 symmetric metasurfaces, simulating the mutual interference process between modes. Additionally, breaking the C4 symmetry enhances the mirror asymmetry, and imparts distinct chiral properties in the far-field during the experimental process. This research demonstrates promising applications in diverse fields, including biological monitoring, light modulation, sensing, and nonlinear enhancement.

Layer-by-layer nanoparticle encapsulating all-trans retinoic acid and CpG as a mucosal adjuvant targeting colorectal cancer.

Colorectal cancer (CRC) ranks among the most prevalent cancers globally, demanding innovative therapeutic strategies. Immunotherapy, a promising avenue, employs cancer vaccines to activate the immune system against tumors. However, conventional approaches fall short of eliciting robust responses within the gastrointestinal (GI) tract, where CRC originates. Harnessing the potential of all-trans retinoic acid (ATRA) and cytosine-phosphorothioate-guanine (CpG), we developed layered nanoparticles using a layer-by-layer assembly method to co-deliver these agents. ATRA, crucial for gut immunity, was efficiently encapsulated alongside CpG within these nanoparticles. Administering these ATRA@CpG-NPs, combined with ovalbumin peptide (OVA), effectively inhibited orthotopic CRC growth in mice. Our approach leveraged the inherent benefits of ATRA and CpG, demonstrating superior efficacy in activating dendritic cells, imprinting T cells with gut-homing receptors, and inhibiting tumor growth. This mucosal adjuvant presents a promising strategy for CRC immunotherapy, showcasing the potential for targeting gut-associated immune responses in combating colorectal malignancies.

All-Trans-Retinoic Acid-Adjuvanted mRNA Vaccine Induces Mucosal Anti-Tumor Immune Responses for Treating Colorectal Cancer.

Messenger RNA (mRNA) cancer vaccines are a new class of immunotherapies that can activate the immune system to recognize and destroy cancer cells. However, their effectiveness in treating colorectal cancer located on the mucosal surface of the gut is limited due to the insufficient activation of mucosal immune response and inadequate infiltration of cytotoxic T cells into tumors. To address this issue, a new mRNA cancer vaccine is developed that can stimulate mucosal immune responses in the gut by co-delivering all-trans-retinoic acid (ATRA) and mRNA using lipid nanoparticle (LNP). The incorporation of ATRA has not only improved the mRNA transfection efficiency of LNP but also induced high expression of gut-homing receptors on vaccine-activated T cells. Additionally, the use of LNP improves the aqueous solubility of ATRA, eliminating the need for toxic solvents to administer ATRA. Upon intramuscular injections, ATRA-adjuvanted mRNA-LNP significantly increase the infiltration of antigen-specific, cytotoxic T cells in the lamina propria of the intestine, mesenteric lymph nodes, and orthotopic colorectal tumors, resulting in significantly improved tumor inhibition and prolonged animal survival compared to conventional mRNA-LNP without ATRA. Overall, this study provides a promising approach for improving the therapeutic efficacy of mRNA cancer vaccines against colorectal cancer.

VO2 Films Decorated with an MXene Interface for Decreased-Power-Triggered Terahertz Modulation.

VO2, which exhibits semiconductor-metal phase transition characteristics occurring on a picosecond time scale, holds great promise for ultrafast terahertz modulation in next-generation communication. However, as of now, there is no reported prototype for an ultrafast device. The temperature effect has been proposed as one of the major obstacles. Consequently, reducing the excitation threshold for the phase transition would be highly significant. The traditional strategy typically involves chemical doping, but this approach often leads to a decrease in phase transition amplitude and a slower transition speed. In this work, we proposed a design featuring a highly conductive MXene interfacial layer between the VO2 film and the substrate. We demonstrate a significant reduction in the phase transition threshold for both temperature and laser-induced phase transition by adjusting the conductivity of the MXene layers with varying thicknesses. Our observations show that the phase transition temperature can be decreased by 9 °C, while the pump fluence for laser excitation can be reduced by as high as 36%. The ultrafast phase transition process on a picosecond scale, as revealed by the optical-pump terahertz-probe method, suggests that the MXene layers have minimal impact on the phase transition speed. Moreover, the reduced phase transition threshold can remarkably alleviate the photothermal effect and inhibit temperature rise and diffusion in VO2 triggered by laser. This study offers a blueprint for designing VO2/MXene hybrid films with reduced phase transition thresholds. It holds significant potential for the development of low-power, intelligent optical and electrical devices including, but not limited to, terahertz modulators based on phase transition phenomena.

A Synergistic Lipid Nanoparticle Encapsulating mRNA Shingles Vaccine Induces Potent Immune Responses and Protects Guinea Pigs from Viral Challenges.

Shingles is caused by the reactivation of varicella zoster virus (VZV) and manifests as painful skin rashes. While the recombinant protein-based vaccine proves highly effective, it encounters supply chain challenges due to a shortage of the necessary adjuvant. Messenger RNA (mRNA)-based vaccines can be rapidly produced on a large scale, but their effectiveness relies on efficient delivery and sequence design. Here, an mRNA-based VZV vaccine using a synergistic lipid nanoparticle (Syn-LNP) containing two different ionizable lipids is developed. Syn-LNP shows superior mRNA expression compared to LNPs formulated with either type of ionizable lipid and to a commercialized LNP. After encapsulating VZV glycoprotein E (gE)-encoding mRNA, mgE@Syn-LNP induces robust humoral and cellular immune responses in two strains of mice. The magnitude of these responses is similar to that induced by adjuvanted recombinant gE proteins and significantly higher than that observed with live-attenuated VZV. mgE@Syn-LNP exhibits durable humoral responses for over 7 months without obvious adverse effects. In addition, mgE@Syn-LNP protects vaccinated guinea pigs against live VZV challenges. Preliminary studies on the mRNA antigen design reveal that the removal of glycosylation sites of gE greatly reduces its immune responses. Collectively, Syn-LNP encapsulating gE-encoded mRNA holds great promise as a shingles vaccine.

A fluorinated ionizable lipid improves the mRNA delivery efficiency of lipid nanoparticles.

The efficacy of messenger RNA (mRNA)-based vaccines or therapies relies on delivery vehicles that can transport them into the cytosol of cells. Lipid nanoparticles (LNPs) are the most clinically advanced carrier for mRNA. The chemical structure of an ionizable lipid is critical for the delivery efficiency of the LNPs. Herein, we synthesize a new ionizable lipid containing fluorinated alkyl chains (F-L319) and evaluate its mRNA delivery efficiency compared to its hydrocarbon counterpart (L319). While LNPs formulated with F-L319 alone showed decreased mRNA encapsulation and delivery efficiencies in comparison to the L319-LNP, we found that combining the appropriate ratios of F-L319 and L319 as hybrid ionizable lipids in LNPs (hybrid-LNPs) greatly enhanced mRNA delivery efficiency both in vitro and in vivo. Upon intravenous injection, the hybrid-LNP showed targeted mRNA expression in the spleen. Mechanistic studies indicate that the enhanced mRNA delivery of the hybrid-LNP is attributed to both improved mRNA encapsulation and cellular uptake. Collectively, fluorination of ionizable lipids represents a promising strategy to improve the delivery efficiency of LNPs.

Increase Nebulization Stability of Lipid Nanoparticles by Integrating a DNA Supramolecular Hydrogel.

Nebulized lipid nanoparticles (LNPs) have been considered as potential therapies for genetic disease as well as infectious disease. However, the sensitivity of LNPs to high shear stress during the nebulization process results in loss of the integrity of the nanostructure and the capability of delivering active pharmaceutical ingredients. Herein we have provided a fast extrusion method to prepare liposomes incorporated with a DNA hydrogel (hydrogel-LNPs) to improve the stability of the LNPs. Taking advantage of the good cellular uptake efficiency, we also demonstrated the potential of hydrogel-LNPs in delivering small molecular doxorubicin (Dox) and nucleic acid drugs. This work provides not only highly biocompatible hydrogel-LNPs for aerosol delivery, but also a strategy to regulate the elasticity of LNPs, which will benefit the potential optimization of drug delivery carriers.

Thermal and mechanical THz modulation of flexible all-dielectric metamaterial.

The implementation of Terahertz (THz) modulation is critical for applications in high-speed wireless communications, security screening and so on. Therefore, it is particularly significant to obtain THz wave modulation devices with stable and flexible performance, easy manipulation of the modulation method, and multi-functionality. Here, we propose a flexible all-dielectric metamaterial by embedding zirconia (ZrO2) microspheres into a vanadium dioxide/polydimethylsiloxane (VO2/PDMS) composite, which can achieve thermal and mechanical tuning of THz wave transmission. When the temperature of the ZrO2/VO2/PDMS metamaterial increases, VO2 changes from the insulating phase to the metallic phase, and the 1st (at 0.304 THz) and 2nd (at 0.414 THz) order magnetic resonances exhibit the tunability of 20 GHz and 15 GHz, respectively. When stretched, the 1st and 2nd order magnetic resonances show the tunability of 12 GHz and 10 GHz, respectively. In the meantime, there are accompanying changes in transmittance at the resonances. The ZrO2/VO2/PDMS all-dielectric metamaterial presented in this work provides an alternative strategy for developing actively tunable, flexible, and versatile THz devices. In addition, it has the merits of simple preparation and low cost, promising large-area and rapid preparation of meta-arrays.

Highly Flexible Ti3C2Tx MXene/Waterborne Polyurethane Membranes for High-Efficiency Terahertz Modulation with Low Insertion Loss.

The dynamic control of terahertz (THz) wave transmission on flexible functional materials is a fundamental building block for wearable electronics and sensors in the THz range. However, achieving high-efficiency THz modulation and low insertion loss is a great challenge while maintaining the excellent flexibility and stretchability of the materials. Herein, we report a Ti3C2Tx MXene/waterborne polyurethane (WPU) membrane prepared by a vacuum-assisted filtration method, which exhibits excellent THz modulation properties across stretching. The hydrophilic Ti3C2Tx MXene and WPU enable the uniform 3D distribution of Ti3C2Tx MXene in the WPU matrix. Particularly, the stretchability with the maximum strain of the membranes can reach 200%, accompanied by dynamic tuning of THz transmittance for more than 90% and an insertion loss as low as -4.87 dB. The giant THz modulation continuously decreases with MXene content per unit area, accompanied by a lower density of the MXene interface and diminished THz absorption during stretching. Such a design opens a pathway for achieving flexible THz modulators with a high modulation depth and low insertion loss, which would be used for THz flexible and wearable devices.

Metal-organic frameworks-based microtrapper for real-time monitoring of targeted analyte and mechanism study.

Interstitial fluid (ISF) provides important information of clinical value and physiological significance beyond blood tests for obtaining more precise health information and disease theranostics. Generally, current strategies are limited to simple extraction with time-consuming follow-up procedures. Facing challenges in efficient and real-time monitoring of target analytes in transdermal ISF, we develop metal-organic framework (MOF)-functionalized microneedle (MN) patches to achieve efficient antibiotics sampling, coupling direct analysis in real time mass spectrometry (DART-MS). The MOF MN microtrapper is constructed in a double-layered structure with a hard core and a better tissue penetration was accomplished. The MOF-based microtrapper manifests good in-vitro and in-vivo antibiotics tracking capability with a semi-quantitative method established. Moreover, the hydrogen-bond driven interaction is clarified by using molecular dynamics simulations (MDS) and related computational analysis. Good penetration safety is confirmed by histological analysis with promising clinical transnationality. We anticipate MOF MN-based microdevices provide a versatile minimally invasive strategy for transdermal ISF extraction and an extendable platform for a range of target molecules monitoring, including drugs, metabolites, biomarkers, et c, with promising clinical transnationality.

Terahertz switchable VO2-Au hybrid active metasurface holographic encryption.

The combination of metasurface and holographic technology is the most cutting-edge development, but most of the proposed designs are static and do not allow active changes through external stimulation after fabrication, which takes only a limited part of the advantage provided by metasurface. Here, we propose and demonstrate a switchable hybrid active metasurface hologram in the terahertz (THz) regime composed of dynamic pixels (VO2-CSRR) and static pixels (Au-CSRR) based on an intelligent algorithm, which can display some/all information in different temperature ranges. In particular, such performance shows excellent potential in the field of optical communication security, making it a promising candidate. To prove this possibility, we propose a scheme for optical information encryption/decryption and transmission, which takes metasurfaces as carriers of encrypted information and state/polarization/positions as the secret key components. Only when the two matches correctly can we get the hidden real information. The security of our proposed scheme has reached an unprecedented level, providing a new road for communication security.

Targeting oncogenic KRAS with molecular brush-conjugated antisense oligonucleotides.

The mutant form of the guanosine triphosphatase (GTPase) KRAS is a key driver in human tumors but remains a challenging therapeutic target, making KRASMUT cancers a highly unmet clinical need. Here, we report a class of bottlebrush polyethylene glycol (PEG)-conjugated antisense oligonucleotides (ASOs) for potent in vivo KRAS depletion. Owing to their highly branched architecture, these molecular nanoconstructs suppress nearly all side effects associated with DNA-protein interactions and substantially enhance the pharmacological properties of the ASO, such as plasma pharmacokinetics and tumor uptake. Systemic delivery to mice bearing human non-small-cell lung carcinoma xenografts results in a significant reduction in both KRAS levels and tumor growth, and the antitumor performance well exceeds that of current popular ASO paradigms, such as chemically modified oligonucleotides and PEGylation using linear or slightly branched PEG. Importantly, these conjugates relax the requirement on the ASO chemistry, allowing unmodified, natural phosphodiester ASOs to achieve efficacy comparable to that of chemically modified ones. Both the bottlebrush polymer and its ASO conjugates appear to be safe and well tolerated in mice. Together, these data indicate that the molecular brush-ASO conjugate is a promising therapeutic platform for the treatment of KRAS-driven human cancers and warrant further preclinical and clinical development.

Mild Acidosis-Directed Signal Amplification in Tumor Microenvironment via Spatioselective Recruitment of DNA Amplifiers.

DNA biotechnology offers intriguing opportunities for amplification-based sensitive detection. However, spatiotemporally-controlled manipulation of signal amplification for in situ imaging of the tumor microenvironment remains an outstanding challenge. Here, we demonstrate a DNA-based strategy that can spatial-selectively amplify the acidic signal in the extracellular milieu of the tumor to achieve specific imaging with improved sensitivity. The strategy, termed mild acidosis-targeted amplification (MAT-amp), leverages the specific acidic microenvironment to engineer tumor cells with artificial DNA receptors through a pH (low) insertion peptide, which permits controlled recruitment of fluorescent amplifiers via a hybridization chain reaction. The acidosis-responsive amplification cascade enables significant fluorescence enhancement in tumors with a reduced background signal in normal tissues, leading to improved signal-to-background ratio. These results highlight the utility of MAT-amp for in situ imaging of the microenvironment characterized by pH disequilibrium.

Micromolding of Thermoplastic Polymers for Direct Fabrication of Discrete, Multilayered Microparticles.

Soft lithography provides a convenient and effective method for the fabrication of microdevices with uniform size and shape. However, formation of an embossed, connective film as opposed to discrete features has been an enduring shortcoming associated with soft lithography. Removing this residual layer requires additional postprocessing steps that are often incompatible with organic materials. This limits adaptation and widespread realization of soft lithography for broader applications particularly in drug discovery and drug delivery fields. A novel and versatile approach is demonstrated that enables fabrication of discrete, multilayered, fillable, and harvestable microparticles directly from any thermoplastic polymer, even at very high molecular weights. The approach, isolated microparticle replication via surface-segregating polymer blend mold, utilizes a random copolymer additive, designed with a highly fluorinated segment that, when blended with the mold's matrix, spontaneously orients to the surface conferring an extremely low surface energy and nonwetting properties to the template. The extremely nonwetting properties of the mold are further utilized to load soluble biologics directly into the built-in microwells in a rapid and efficient manner using an innovative screen-printing approach. It is believed that this approach holds promise for fabrication of large-array, 3D, complex microstructures, and is a significant step toward clinical translation of microfabrication technologies.

Two-Pronged Intracellular Co-Delivery of Antigen and Adjuvant for Synergistic Cancer Immunotherapy.

Nanovaccines have emerged as promising alternatives or complements to conventional cancer treatments. Despite the progresses, specific co-delivery of antigen and adjuvant to their corresponding intracellular destinations for maximizing the activation of antitumor immune responses remains a challenge. Herein, a lipid-coated iron oxide nanoparticle is delivered as nanovaccine (IONP-C/O@LP) that can co-deliver peptide antigen and adjuvant (CpG DNA) into cytosol and lysosomes of dendritic cells (DCs) through both membrane fusion and endosome-mediated endocytosis. Such two-pronged cellular uptake pattern enables IONP-C/O@LP to synergistically activate immature DCs. Iron oxide nanoparticle also exhibits adjuvant effects by generating intracellular reactive oxygen species, which further promotes DC maturation. IONP-C/O@LP accumulated in the DCs of draining lymph nodes effectively increases the antigen-specific T cells in both tumor and spleen, inhibits tumor growth, and improves animal survival. Moreover, it is demonstrated that this nanovaccine is a general platform of delivering clinically relevant peptide antigens derived from human papilloma virus 16 to trigger antigen-specific immune responses in vivo.

Doxorubicin and CpG loaded liposomal spherical nucleic acid for enhanced Cancer treatment.

Chemotherapeutics that can trigger immunogenic cell death (ICD) and release tumor-specific antigens are effective on treating a variety of cancers. The codelivery of chemotherapeutics with adjuvants is a promising strategy to achieve synergistic therapeutic effect. However, low drug loading and complicated preparation of current delivery systems lead to carrier-associated toxicity and immunogenicity. Herein, we developed a facile approach to construct liposomal spherical nucleic acids (SNA) by the self-assembly of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)-doxorubicin conjugate and DOPE-matrix metalloproteinases-9 (MMP-9) responsive peptide-CpG conjugate (DOPE-MMP-CpG). Liposomal SNAs efficiently co-delivered DOX and CpG into tumors and released the two drugs upon biological stimuli of MMP-9 enzyme in tumor microenvironment (TME) and high concentration of endogenous glutathione in tumor cells. We demonstrated that liposomal SNA enhanced activation of dendritic cells (DCs), promoted expansion of CD8+ and CD4+ T cells in both tumors and spleen, inhibited tumor growth, and extended animal survival. This work provided a simple strategy of delivering chemotherapeutics and adjuvants to tumors with synergistic therapeutic effect and reduced side effect.

Volatile and Nonvolatile Switching of Phase Change Material Ge2Sb2Te5 Revealed by Time-Resolved Terahertz Spectroscopy.

Phase change materials exhibit unique advantages in reconfigurable photonic devices due to drastic tunability of photoelectric properties. Here, we systematically investigate the thermal equilibrium process and the ultrafast dynamics of Ge2Sb2Te5 (GST) driven by femtosecond (fs) pulses, using time-resolved terahertz spectroscopy. Both fs-pulse-driven crystallization and amorphization are demonstrated, and the threshold of photoinduced crystallization (amorphization) is determined to be 8.4 mJ/cm2 (10.1 mJ/cm2). The ultrafast carrier dynamics reveal that the cumulative photothermal effect plays a crucial role in the ultrafast crystallization, and modulation depth of volatile (nonvolatile) THz has switching limits up to 30% (15%). A distinctive phonon absorption at 1.1 THz is observed, providing fingerprint spectrum evidence of crystalline lattice formation driven by intense fs pulses. Finally, multistate volatile (nonvolatile) THz switching is implemented by tuning optical pump fluence. These results provide insight into the photoinduced phase change of GST and offer benefits for all optical THz functional devices.

Reconfigurable Optical Physical Unclonable Functions Enabled by VO2 Nanocrystal Films.

Optical physical unclonable function (PUF) is one of the most promising hardware security solutions, which has been proven to be resistant to machine learning attacks. However, the disordered structures of the traditional optical PUFs are usually deterministic once they are manufactured and therefore exhibit fixed challenge-response behaviors. Herein, a reconfigurable PUF (R-PUF) is proposed and demonstrated by using the reversible phase transition behavior of VO2 nanocrystals combined with TiO2 disordered nanoparticles. Both the simulation and experiment results show that the near-infrared laser speckle pattern of the R-PUF can be almost completely altered after the phase transition of VO2 nanocrystals, resulting in a reconfigurable and reproducible optical response. The similarity of the response speckles shows an obvious hysteresis loop during the rise and drop of temperature, providing a simple way to regulate and control the response behaviors of the R-PUF. More importantly, the hysteretic characteristic provides a new dimension to describe the challenge-response behavior of the R-PUF besides the laser speckle, providing an effective way to improve the security and encoding capacity of the optical PUFs. The proposed R-PUF can be employed as a promising security primitive for high robustness and high-security authentication and encryption.

Polymeric PD-L1 blockade nanoparticles for cancer photothermal-immunotherapy.

Checkpoint inhibitors, such as antibodies blocking the PD-1/PD-L1 pathway, are among the most promising immunotherapies to treat metastatic cancers, but their response rate remains low. In addition, the usage of monoclonal antibodies as checkpoint inhibitors is associated with a series of drawbacks. Herein, an all synthetic nanoparticle with PD-L1 blockade capability is developed for cancer photothermal-immunotherapy. The polymeric nanoparticle integrates photothermal treatment, antitumor vaccination, and PD-1/PD-L1 blockade in a single system to augment the antitumor efficacy. In a CT26 bilateral tumor model, intravenously injected nanoparticles accumulate in tumor sites and mediate strong photothermal effects, eradicate the NIR treated primary tumors and elicit strong antitumor immunity by inducing immunogenic cell death (ICD). Growth of the untreated distant tumors is also suppressed due to the synergies of systemic antitumor immune activation and PD-L1 blockade. Our strategy offers a simple but promising approach for the treatment of metastatic cancer.