Reprogramming the genome of M13 bacteriophage for all-in-one personalized cancer vaccine.

Peptide-based vaccines face limitations in immunogenicity and stability, and challenges in co-delivering antigens and adjuvants effectively. Virus-based nanoparticles, particularly M13 bacteriophage, present a promising solution due to their genetic modifiability, intrinsic adjuvanticity, and efficient antigen presentation capabilities. Here we developed a programmable M13 phage-based personalized cancer vaccine enabling single-step antigen-adjuvant assembly.

A Machine Learning-Optimized System for Pulsatile, Photo- and Chemotherapeutic Treatment Using Near-Infrared Responsive MoS-Based Microparticles in a Breast Cancer Model.

Multimodal cancer therapies are often required for progressive cancers due to the high persistence and mortality of the disease and the negative systemic side effects of traditional therapeutic methods. Thus, the development of less invasive modalities for recurring treatment cycles is of clinical significance. Herein, a light-activatable microparticle system was developed for localized, pulsatile delivery of anticancer drugs with simultaneous thermal ablation by applying controlled ON-OFF thermal cycles using near-infrared laser irradiation.

Noninvasive Imaging of T-Cells during Cancer Immunotherapy Using Rare-Earth Nanoparticles.

Only a minority of patients respond positively to cancer immunotherapy, and addressing this variability is an active area of immunotherapy research. Infiltration of tumors by immune cells is one of the most significant prognostic indicators of response and disease-free survival. However, the ability to noninvasively sample the tumor microenvironment for immune cells remains limited.

A Machine Learning-optimized system for on demand, pulsatile, photo- and chemo-therapeutic treatment using near-infrared responsive MoS -based microparticles in a breast cancer model.

Cancer therapy research is of high interest because of the persistence and mortality of the disease and the side effects of traditional therapeutic methods, while often multimodal treatments are necessary based on the patient's needs. The development of less invasive modalities for recurring treatment cycles is thus of critical significance. Herein, a light-activatable microparticle system was developed for localized, pulsatile delivery of anticancer drugs with simultaneous thermal ablation, by applying controlled ON-OFF thermal cycles using near-infrared laser irradiation.

Engineering a Two-Component Hemostat for the Treatment of Internal Bleeding through Wound-Targeted Crosslinking.

Primary hemostasis (platelet plug formation) and secondary hemostasis (fibrin clot formation) are intertwined processes that occur upon vascular injury. Researchers have sought to target wounds by leveraging cues specific to these processes, such as using peptides that bind activated platelets or fibrin. While these materials have shown success in various injury models, they are commonly designed for the purpose of treating solely primary or secondary hemostasis.

STING Protein-Based In Situ Vaccine Synergizes CD4 T, CD8 T, and NK Cells for Tumor Eradication.

Stimulator of interferon genes (STING) signaling is a promising target in cancer immunotherapy, with many ongoing clinical studies in combination with immune checkpoint blockade (ICB). Existing STING-based therapies largely focus on activating CD8 T cell or NK cell-mediated cytotoxicity, while the role of CD4 T cells in STING signaling has yet to be extensively studied in vivo. Here, a distinct CD4-mediated, protein-based combination therapy of STING and ICB as an in situ vaccine, is reported.

A new label-free optical imaging method for the lymphatic system enhanced by deep learning.

Unlabelled: Our understanding of the lymphatic vascular system lags far behind that of the blood vascular system, limited by available imaging technologies. We present a label-free optical imaging method that visualizes the lymphatic system with high contrast. We developed an orthogonal polarization imaging (OPI) in the shortwave infrared range (SWIR) and imaged both lymph nodes and lymphatic vessels of mice and rats through intact skin, as well as human mesenteric lymph nodes in colectomy specimens.

Surface Plasmon Enhanced Upconversion Fluorescence in Short-Wave Infrared for In Vivo Imaging of Ovarian Cancer.

Short-wave infrared (SWIR; 850-1700 nm) upconversion fluorescence enables "autofluorescence-free" imaging with minimal tissue scattering, yet it is rarely explored due to the lack of strongly emissive SWIR upconversion fluorophores. In this work, we apply SWIR upconversion fluorescence for in vivo imaging with exceptional image contrast. Gold nanorods (AuNRs) are used to enhance the SWIR upconversion emission of small organic dyes, forming a AuNR-dye nanocomposite (NC).

Phage Particles of Controlled Length and Genome for Targeted Glioblastoma Imaging and Therapeutic Delivery.

M13 bacteriophage (phage) are versatile, genetically tunable nanocarriers that have been recently adapted for use as diagnostic and therapeutic platforms. Applying p3 capsid chlorotoxin fusion with the "" circular single-stranded DNA (cssDNA) gene packaging system, we produced miniature chlorotoxin (CTX-) phage particles with a minimum length of 50 nm that can target intracranial orthotopic patient-derived GBM22 glioblastoma tumors in the brains of mice. Systemically administered indocyanine green conjugated CTX- phage accumulated in brain tumors, facilitating shortwave infrared detection.

Peptide-Based Cancer Vaccine Delivery via the STINGΔTM-cGAMP Complex.

With the advent of bioinformatic tools in efficiently predicting neo-antigens, peptide vaccines have gained tremendous attention in cancer immunotherapy. However, the delivery of peptide vaccines remains a major challenge, primarily due to ineffective transport to lymph nodes and low immunogenicity. Here, a strategy for peptide vaccine delivery is reported by first fusing the peptide to the cytosolic domain of the stimulator of interferon genes protein (STINGΔTM), then complexing the peptide-STINGΔTM protein with STING agonist 2'3' cyclic guanosine monophosphate-adenosine monophosphate (cGAMP).

A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity.

Saponins are potent and safe vaccine adjuvants, but their mechanisms of action remain incompletely understood. Here, we explored the properties of several saponin formulations, including immune-stimulatory complexes (ISCOMs) formed by the self-assembly of saponin and phospholipids in the absence or presence of the Toll-like receptor 4 agonist monophosphoryl lipid A (MPLA). We found that MPLA self-assembles with saponins to form particles physically resembling ISCOMs, which we termed saponin/MPLA nanoparticles (SMNP).

Structural ceramic batteries using an earth-abundant inorganic waterglass binder.

Sodium trisilicate waterglass is an earth-abundant inorganic adhesive which binds to diverse materials and exhibits extreme chemical and temperature stability. Here we demonstrate the use of this material as an electrode binder in a lay-up based manufacturing system to produce structural batteries. While conventional binders for structural batteries exhibit a trade-off between mechanical and electrochemical performance, the waterglass binder is rigid, adhesive, and facilitates ion transport.

Surface Plasmon-Enhanced Short-Wave Infrared Fluorescence for Detecting Sub-Millimeter-Sized Tumors.

Short-wave infrared (SWIR, 900-1700 nm) enables in vivo imaging with high spatiotemporal resolution and penetration depth due to the reduced tissue autofluorescence and decreased photon scattering at long wavelengths. Although small organic SWIR dye molecules have excellent biocompatibility, they have been rarely exploited as compared to their inorganic counterparts, mainly due to their low quantum yield. To increase their brightness, in this work, the SWIR dye molecules are placed in close proximity to gold nanorods (AuNRs) for surface plasmon-enhanced emission.

Simulating selective binding of a biological template to a nanoscale architecture: a core concept of a clamp-based binding-pocket-favored N-terminal-domain assembly.

The biological template and its mutants have vital significance in next generation remediation, electrochemical, photovoltaic, catalytic, sensing and digital memory devices. However, a microscopic model describing the biotemplating process is generally lacking on account of modelling complexity, which has prevented widespread commercial use of biotemplates. Here, we demonstrate M13-biotemplating kinetics in atomic resolution by leveraging large-scale molecular dynamics (MD) simulations.

Designing yeast as plant-like hyperaccumulators for heavy metals.

Hyperaccumulators typically refer to plants that absorb and tolerate elevated amounts of heavy metals. Due to their unique metal trafficking abilities, hyperaccumulators are promising candidates for bioremediation applications. However, compared to bacteria-based bioremediation systems, plant life cycle is long and growing conditions are difficult to maintain hindering their adoption.

Virus-Templated Nickel Phosphide Nanofoams as Additive-Free, Thin-Film Li-Ion Microbattery Anodes.

Transition metal phosphides are a new class of materials generating interest as alternative negative electrodes in lithium-ion batteries. However, metal phosphide syntheses remain underdeveloped in terms of simultaneous control over phase composition and 3D nanostructure. Herein, M13 bacteriophage is employed as a biological scaffold to develop 3D nickel phosphide nanofoams with control over a range of phase compositions and structural elements.

Thermally robust solvent-free biofluids of M13 bacteriophage engineered for high compatibility with anhydrous ionic liquids.

Here, we demonstrate a chemical modification strategy to create biomaterials of the M13 bacteriophage with extraordinary thermal stability, and high compatibility with non-aqueous ionic liquids. The results provide a blueprint for developing soft materials with well-defined architectures that may find broad applicability in the next generation of flexible devices.

Creating fluorescent quantum defects in carbon nanotubes using hypochlorite and light.

Covalent doping of single-walled carbon nanotubes (SWCNTs) can modify their optical properties, enabling applications as single-photon emitters and bio-imaging agents. We report here a simple, quick, and controllable method for preparing oxygen-doped SWCNTs with desirable emission spectra. Aqueous nanotube dispersions are treated at room temperature with NaClO (bleach) and then UV-irradiated for less than one minute to achieve optimized O-doping.

M13 Virus-Based Framework for High Fluorescence Enhancement.

Fluorescence imaging is a powerful tool for studying biologically relevant macromolecules, but its applicability is often limited by the fluorescent probe, which must demonstrate both high site-specificity and emission efficiency. In this regard, M13 virus, a versatile biological scaffold, has previously been used to both assemble fluorophores on its viral capsid with molecular precision and to also target a variety of cells. Although M13-fluorophore systems are highly selective, these complexes typically suffer from poor molecular detection limits due to low absorption cross-sections and moderate quantum yields.

Real-Time Single-Walled Carbon Nanotube-Based Fluorescence Imaging Improves Survival after Debulking Surgery in an Ovarian Cancer Model.

Improved cytoreductive surgery for advanced stage ovarian cancer (OC) represents a critical challenge in the treatment of the disease. Optimal debulking reaching no evidence of macroscopic disease is the primary surgical end point with a demonstrated survival advantage. Targeted molecule-based fluorescence imaging offers complete tumor resection down to the microscopic scale.

Deep-tissue optical imaging of near cellular-sized features.

Detection of biological features at the cellular level with sufficient sensitivity in complex tissue remains a major challenge. To appreciate this challenge, this would require finding tens to hundreds of cells (a 0.1 mm tumor has ~125 cells), out of ~37 trillion cells in the human body.

Highly adjustable 3D nano-architectures and chemistries via assembled 1D biological templates.

Porous metal nanofoams have made significant contributions to a diverse set of technologies from separation and filtration to aerospace. Nonetheless, finer control over nano and microscale features must be gained to reach the full potential of these materials in energy storage, catalytic, and sensing applications. As biologics naturally occur and assemble into nano and micro architectures, templating on assembled biological materials enables nanoscale architectural control without the limited chemical scope or specialized equipment inherent to alternative synthetic techniques.

DNA Origami and G-Quadruplex Hybrid Complexes Induce Size Control of Single-Walled Carbon Nanotubes via Biological Activation.

DNA self-assembly has enabled the programmable fabrication of nanoarchitectures, and these nanoarchitectures combined with nanomaterials have provided several applications. Here, we develop an approach for cutting single-walled carbon nanotubes (SWNTs) of predetermined lengths, using DNA origami and G-quadruplex hybrid complexes. This approach is based on features of DNA: (1) wrapping SWNTs with DNA to improve the dispersibility of SWNTs in water; (2) using G-quadruplex DNA to confine hemin in close proximity to SWNTs and enhance the biological activation of hydrogen peroxide by hemin; and (3) forming DNA origami platforms to allow for the precise placement of G-quadruplexes, enabling size control.

Harnessing the hygroscopic and biofluorescent behaviors of genetically tractable microbial cells to design biohybrid wearables.

Cells' biomechanical responses to external stimuli have been intensively studied but rarely implemented into devices that interact with the human body. We demonstrate that the hygroscopic and biofluorescent behaviors of living cells can be engineered to design biohybrid wearables, which give multifunctional responsiveness to human sweat. By depositing genetically tractable microbes on a humidity-inert material to form a heterogeneous multilayered structure, we obtained biohybrid films that can reversibly change shape and biofluorescence intensity within a few seconds in response to environmental humidity gradients.