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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). A maximal enhancement factor of ∼1320, contributed by both excitation and radiative decay rate enhancement, is achieved by varying the dye-to-AuNR ratio. In addition, the upconversion emission intensity of both free dyes and AuNR-dye NCs depends linearly on the excitation power, indicating that the upconversion emission mechanism remains unchanged upon enhancement, and it involves one-photon absorption. Moreover, the SWIR upconversion emission shows a significantly higher signal contrast than downconversion emission in the same emission window in a nonscattering medium. Finally, we apply the surface plasmon enhanced SWIR upconversion fluorescence for in vivo imaging of ovarian cancer, demonstrating high image contrast and low required dosage due to the suppressed autofluorescence.

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. The system is composed of poly(caprolactone) microparticles of 200 μm size with incorporated molybdenum disulfide (MoS2) nanosheets as the photothermal agent and hydrophilic doxorubicin or hydrophobic violacein, as model drugs. Upon irradiation the nanosheets heat up to ≥50 °C leading to polymer matrix melting and release of the drug. MoS2nanosheets exhibit high photothermal conversion efficiency and allow for application of low power laser irradiation for the system activation. A Machine Learning algorithm was applied to acquire optimal laser operation conditions; 0.4 W/cm2laser power at 808 nm, 3-cycle irradiation, for 3 cumulative minutes. In a mouse subcutaneous model of 4T1 triple-negative breast cancer, 25 microparticles were intratumorally administered and after 3-cycle laser treatment the system conferred synergistic phototherapeutic and chemotherapeutic effect. Our on-demand, pulsatile synergistic treatment resulted in increased median survival up to 40 days post start of treatment compared to untreated mice, with complete eradication of the tumors at the primary site. Such a system could have potential for patients in need of recurring cycles of treatment on subcutaneous tumors.GRAPHICAL ABSTRACT

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). The process results in the formation of self-assembled cGAMP-peptide-STINGΔTM tetramers, which enables efficient lymphatic trafficking of the peptide. Moreover, the cGAMP-STINGΔTM complex acts not only as a protein carrier for the peptide, but also as a potent adjuvant capable of triggering STING signaling independent of endogenous STING protein-an especially important attribute considering that certain cancer cells epigenetically silence their endogenous STING expression. With model antigen SIINFEKL, it is demonstrated that the platform elicits effective STING signaling in vitro, draining lymph node targeting in vivo, effective T cell priming in vivo as well as antitumoral immune response in a mouse colon carcinoma model, providing a versatile solution to the challenges faced in peptide vaccine delivery.

Our demand for electronic goods and fossil fuels has challenged our ecosystem with contaminating amounts of heavy metals, causing numerous water sources to become polluted. To counter heavy-metal waste, industry has relied on a family of physicochemical processes, with chemical precipitation being one of the most commonly used. However, the disadvantages of chemical precipitation are vast, including the generation of secondary waste, technical handling of chemicals and need for complex infrastructures. To circumvent these limitations, biological processes to naturally manage waste have been sought. Here, we show that yeast can act as a biological alternative to traditional chemical precipitation by controlling naturally occurring production of hydrogen sulfide (H2S). Sulfide production was harnessed by controlling the sulfate assimilation pathway, where strategic knockouts and culture conditions generated H2S from 0 to over 1,000 ppm (~30 mM). These sulfide-producing yeasts were able to remove mercury, lead and copper from real-world samples taken from the Athabasca oil sands. More so, yeast surface display of biomineralization peptides helped control for size distribution and crystallinity of precipitated metal sulfide nanoparticles. Altogether, this yeast-based platform not only removes heavy metals but also offers a platform for metal re-extraction through precipitation of metal sulfide nanoparticles. Physicochemical treatments of heavy-metal pollution in waste water have several environmental and structural disadvantages. This Article shows that sulfide-producing yeasts are able to remove mercury, lead and copper from real-world water samples and offer a platform for metal re-extraction.

The ability to treat tumors with high efficacy in a local microenvironment, while mitigating the side effects of systemic toxicity is an area of active investigation. Towards this goal, designing a minimally-invasive local therapeutic modality, with a controlled, pulsatile drug release mechanism is an attractive proposition. In this study, a near-infrared (NIR) photo-activatable microparticle was developed for localized, pulsatile delivery of encapsulated anticancer drugs into the tumor with simultaneous thermal ablation, with controlled ON-OFF thermal cycles using NIR laser irradiation. The microparticles were fabricated using a poly(caprolactone) (PCL) matrix, containing 2D molybdenum disulfide (MoS2) nanosheets as the NIR-responsive photothermal agent, and doxorubicin or violacein, as hydrophilic and hydrophobic model anticancer drugs, respectively. Cubic microparticles of 200 µm size were fabricated by casting a polymer-MoS2-drug film on PDMS mold with loading efficiency of 2 μg MoS2 per particle, and 0.2-8 μg of drug per particle. A cytotoxicity assay was performed to test the efficacy of the loaded microparticles in reducing the viability of 4T1 murine-derived cell culture, using the ON-OFF laser switch mechanism. In order to select a suitable laser power and duration of treatment for in vivo studies, a Machine Learning algorithm based on a Random Forest classifier was trained, to arrive at the optimal treatment conditions: 0.4-0.5 W/cm2 of laser power at 808 nm, for 3 cumulative minutes of laser irradiation, to reach the target temperature of 50 °C, which activates PCL melting and subsequent drug release. The effect of pulsatile treatment was studied in vivo in a murine-derived 4T1 subcutaneous mouse model of breast cancer, using this photo-activatable ON-OFF switch mechanism, for up to 3 cycles of laser irradiation. As control groups, tumor only (no treatment), laser only (no drug or microparticle), drug only (no laser or microparticle), microparticles only (no drug or laser), and microparticles with laser (no drug) were studied. The cohorts receiving the photo-activated 3-cyclic treatment for both drugs showed increased median survival up to 40 days post tumor induction, compared to a median survival of 16 days for the control groups. Although one laser cycle was enough to trigger drug release, there was a significant shrinkage in the tumor volume noticed with 3 cycles, with eventual scarring and shedding of the tissue with no evidence of residual tumor at the primary site. While this cyclic drug release modality is very effective at treating the primary site, subsequent histopathology revealed that the aggressive tumor in some animals had metastasized to the liver and other organs. More work is ongoing to design better targeted approaches to deliver the drug-loaded microparticles to the site of metastatic tumors, to increase the survival prospects of this disease. Citation Format: Maria Kanelli, Neelkanth M. Bardhan, Morteza Sarmadi, Shahad Alsaiari, William Rothwell, Apurva Pardeshi, Angela M. Belcher, Ana Jaklenec, Robert S. Langer. Photo-activatable ON-OFF microparticles for on-demand pulsatile drug delivery in a breast cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 820.

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 immunostimulatory complexes (ISCOMs) formed by the self-assembly of saponin and phospholipids in the absence or presence of the Toll like receptor (TLR) 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). Saponin-containing adjuvants exhibited distinctive mechanisms of action, altering lymph flow in a mast cell-dependent manner and promoting antigen entry into draining lymph nodes. SMNP was particularly effective, exhibiting even greater potency than the compositionally-related adjuvant AS01(B) in mice, and primed robust germinal center B cell, T(FH), and HIV tier 2 neutralizing antibodies in non-human primates. Altogether, these findings shed new light on mechanisms by which saponin adjuvants act to promote the immune response and suggest SMNP may be a promising adjuvant in the setting of HIV, SARS-CoV-2, and other pathogens.

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. The model reveals the assembly of gold nanoparticles on two experimentally-based M13 phage types using full M13-capsid structural models and with polarizable gold nanoparticles in explicit solvent. Both mechanistic and structural insights into the selective binding affinity of the M13 phage to gold nanoparticles are obtained based on a previously unconsidered clamp-based binding-pocket-favored N-terminal-domain assembly and also on surface-peptide flexibility. These results provide a deeper level of understanding of protein sequence-based affinity and open the route for genetically engineering a wide range of 3D electrodes for high-density low-cost device integration.

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. We used a custom-built reflectance/fluorescence imaging system with an orthotopic OC mouse model to both quantify tumor detectability and evaluate the effect of fluorescence image-guided surgery on post-operative survival. The contrast agent is an intraperitoneal injectable nanomolecular probe, composed of single-walled carbon nanotubes, coupled to an M13 bacteriophage carrying a modified peptide binding to the SPARC protein, an extracellular protein overexpressed in OC. The imaging system is capable of detecting a second near-infrared window fluorescence (1000-1700 nm) and can display real-time video imagery to guide intraoperative tumor debulking. We observed high microscopic tumor detection with a pixel-limited resolution of 200 μm. Moreover, in a survival-surgery orthotopic OC mouse model, we demonstrated an increased survival benefit for animals treated with fluorescence image-guided surgical resection compared to standard surgery.

Clean hydrogen production via water electrolysis is incumbent upon the development of high-performing hydrogen evolution reaction electrocatalysts. Despite decades of commercial maturity, however, alkaline water electrolyzers continue to suffer from limitations in electrocatalytic activity and stability, even with noble metal catalysts. In recent years, combining platinum with oxophilic materials, such as metal hydroxides, has shown great promise for improving performance potentially by enabling stronger water dissociation at the surface of electrocatalysts. In this work, we leveraged the nanoscopic proportions and surface programmability of the filamentous M13 bacteriophage in the design, synthesis, and exceptional performance of 3D nanostructured biotemplated electrocatalysts for alkaline hydrogen evolution. We developed a facile synthesis method for phage-templated, Pt–Ni(OH)₂ nanonetworks, relying on scalable techniques like electroless deposition. After optimization of the platinum content, our materials display –4.9 A mg⁻¹Pt at −70 mV versus the reversible hydrogen electrode, the highest reported mass activity in 1 M KOH to date, and undergo minimal changes in overpotential under galvanostatic operation at −10 mA cm⁻²[subscript geo]. Looking forward, the performance of these catalysts suggests that biotemplating nanostructures with M13 bacteriophage offers an interesting new route for developing high-performing electrocatalysts. Keywords: Hydrogen evolution reaction; Electrocatalysis; M13 bacteriophage; 3D nanostructure; Biotemplating, United States. Defense Advanced Research Projects Agency (Award HR0011835402), Shell International Exploration and Production B.V. (Award 4550155123)

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. Near-infrared optical imaging holds promise for high-resolution, deep-tissue imaging, but is limited by autofluorescence and scattering. To date, the maximum reported depth using second-window near-infrared (NIR-II: 1000–1700 nm) fluorophores is 3.2 cm through tissue. Here, we design an NIR-II imaging system, “Detection of Optically Luminescent Probes using Hyperspectral and diffuse Imaging in Near-infrared” (DOLPHIN), that resolves these challenges. DOLPHIN achieves the following: (i) resolution of probes through up to 8 cm of tissue phantom; (ii) identification of spectral and scattering signatures of tissues without apriori knowledge of background or autofluorescence; and (iii) 3D reconstruction of live whole animals. Notably, we demonstrate noninvasive real-time tracking of a 0.1 mm-sized fluorophore through the gastrointestinal tract of a living mouse, which is beyond the detection limit of current imaging modalities.

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. The fluorescence enhancement is optimized by controlling the dye-to-AuNR number ratio and up to ≈45-fold enhancement factor is achieved. In addition, the results indicate that the highest dye-to-AuNR number ratio gives the highest emission intensity per weight and this is used for synthesizing SWIR imaging probes using layer-by-layer (LbL) technique with polymer coating protection. Then, the SWIR imaging probes are applied for in vivo imaging of ovarian cancer and the surface coating effect on intratumor distribution of the imaging probes is investigated in two orthotopic ovarian cancer models. Lastly, it is demonstrated that the plasmon-enhanced SWIR imaging probe has great potential for fluorescence imaging-guided surgery by showing its capability to detect sub-millimeter-sized tumors.

One of the best strategies for achieving faster computers is to mitigate the millisecond-order time delays arising from the transfer and storage of information between silicon- and magnetic-based memories. Segregating-binary-alloy (SBA)-type phase-change materials (PCMs), such as gallium antimonide-based systems, can store information on 10 ns time scales by using a single memory structure; however, these materials are hindered by the high consumption of energies and undergo elemental segregation around 620 K. Nanowire-like PCMs can achieve low-energy consumption but are often synthesized by vapor–liquid–solid methods above 720 K, which would cause irreversible corruption of SBA-based PCMs. Here we control the morphology, composition, and functionality of SBA-type germanium–tin oxide systems using template-driven nucleation that leverages the electrostatic-binding specificity of the M13 bacteriophage surface. A wirelike PCM was achieved, with controllable and reliable phase-changing signatures, capable of...

Sodium-ion batteries (SIBs) have generated substantial interest because of the geopolitical uncertainty of the availability of lithium, as well as the potential cost savings associated with replacing lithium with sodium. One of the key technological impediments to SIBs is the availability of a high-capacity anode material. Here, we show that biotemplated zinc sulfide nanofibers, prepared using the M13 bacteriophage template, have the potential to be used for this purpose. We investigated the effect of both annealing and carbon coating on the electrochemical performance of these materials. Biotemplated zinc sulfide nanofibers, when coated with a few-nanometer carbon layer, could deliver a reversible capacity of 603 mAh/g at 100 mA/g discharge rate, even when the zinc sulfide loading is as high as 70%. The initial Coulombic efficiency reached 71%, and the electrode could be cycled for at least 100 cycles.

Herein, we report a method that uses free-base amino acids to mediate the controlled hydrothermal growth of amorphous zinc oxide (a-ZnO) or nanocrystalline zinc sulfide (c-ZnS) shells on gold nanoparticles. By screening through a set of 13 candidate amino acids, we have identified four as being capable of mediating inorganic shell growth using an aqueous, low-temperature, one-pot process. In particular, unaggregated and monodisperse sols of exceptional quality are produced using l-histidine, which preserves colloidal stability and mediates the growth of continuous and remarkably uniform a-ZnO shells with a tunable thickness between 2 and 25 nm while avoiding the nucleation of free particles. By coupling spectral extinction measurements with generalized Mie theory calculations, we estimated the complex refractive index of the a-ZnO shell to be 1.47 + i0.09. It is expected not only that our Au@a-ZnO core–shell particles are suitable for both energy and biological applications but also that our process for g...

Cell-intrinsic reporters such as luciferase (LUC) and red fluorescent protein (RFP) have been commonly utilized in preclinical studies to image tumor growth and to monitor therapeutic responses. While extrinsic reporters that emit near infrared I (NIR-I: 650–950 nm) or near-infrared II (NIR-II: 1000–1700 nm) optical signals have enabled minimization of tissue autofluorescence and light scattering, it has remained unclear as to whether their use has afforded more accurate tumor imaging in small animals. Here, we developed a novel optical imaging construct comprised of rare earth lanthanide nanoparticles coated with biodegradable diblock copolymers and doped with organic fluorophores, generating NIR-I and NIR-II emissive bands upon optical excitation. Simultaneous injection of multiple spectrally-unique nanoparticles into mice bearing tumor implants established via intraperitoneal dissemination of LUC+/RFP+ OVCAR-8 ovarian cancer cells enabled direct comparisons of imaging with extrinsic vs. intrinsic reporters, NIR-II vs. NIR-I signals, as well as targeted vs. untargeted exogenous contrast agents in the same animal and over time. We discovered that in vivo optical imaging at NIR-II wavelengths facilitates more accurate detection of smaller and earlier tumor deposits, offering enhanced sensitivity, improved spatial contrast, and increased depths of tissue penetration as compared to imaging with visible or NIR-I fluorescent agents. Our work further highlights the hitherto underappreciated enhancements in tumor accumulation that may be achieved with intraperitoneal as opposed to intravenous administration of nanoparticles. Lastly, we found discrepancies in the fidelity of tumor uptake that could be obtained by utilizing small molecules for in vivo as opposed to in vitro targeting of nanoparticles to disseminated tumors.

In recent years, there has been tremendous excitement over the development of new classes of applications for NIR-emitting nanoparticles. These materials have found application in fields diverse as early diagnosis of metastatic cancers, imaging-guided drug delivery and biodistribution studies, photothermal or photodynamic therapy of tumors, non-invasive detection and monitoring of deep-tissue pathogenic infections, and potentiating the antibiotic strength against antibiotic-resistant bacterial infections, to name a few. However, the cornerstone of these applications rests on the successful functionalization of these nanoparticles, in order to render them biocompatible, increase circulation and residence time, and to provide them the necessary targeting capability and enhance the functionality of the imaging agent. Here, we present an in-depth review of the methods used for polymer functionalization of the most common classes of NIR-emitting nanoparticles: organic dyes and small-molecule probes, inorganic quantum dots, gold nanoparticles, carbon dots, carbon nanotubes, graphene and their derivatives, and upconversion or downconversion nanoparticles. By exploring the preclinical studies and the clinical trials (wherever applicable), we investigate the strategies which have been successfully deployed till date, as well as comment on the potential concerns of toxicity arising from the biomedical applications of these nanoparticles.

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. Virus-templated Ni5P4 nanofoams are then integrated as thin-film negative electrodes in lithium-ion microbatteries, demonstrating a discharge capacity of 677 mAh g⁻¹ (677 mAh cm⁻³) and an 80% capacity retention over more than 100 cycles. This strong electrochemical performance is attributed to the virus-templated, nanostructured morphology, which remains electronically conductive throughout cycling, thereby sidestepping the need for conductive additives. When accounting for the mass of additional binder materials, virus-templated Ni₅P₄ nanofoams demonstrate the highest practical capacity reported thus far for Ni₅P₄ electrodes. Looking forward, this synthesis method is generalizable and can enable precise control over the 3D nanostructure and phase composition in other metal phosphides, such as cobalt and copper. Keywords: 3D nanostructure; transition metal phosphide; biotemplating; M13 bacteriophage; Li-ion microbattery, United States. Defense Advanced Research Projects Agency (Grant HR0011835402), National Science Foundation (Grant DMR‐1419807), Shell International Exploration and Production B.V. (Grant 4550155123)

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. The doping efficiency is controlled by varying surfactant concentration and type, NaClO concentration, and irradiation dose. Photochemical action spectra indicate that doping involves reaction of SWCNT sidewalls with oxygen atoms formed by photolysis of ClO− ions. Variance spectroscopy of products reveals that most individual nanotubes in optimally treated samples show both pristine and doped emission. A continuous flow reactor is described that allows efficient preparation of milligram quantities of O-doped SWCNTs. Finally, we demonstrate a bio-imaging application that gives high contrast short-wavelength infrared fluorescence images of vasculature and lymphatic structures in mice injected with only ~100 ng of the doped nanotubes., Creating fluorescent defects in single-walled carbon nanotubes is a promising way to modify their optical properties, but defect generation is still difficult to control. Here, the authors report an efficient method to incorporate high-quality oxygen defects in carbon nanotubes using only hypochlorite and light.

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. ©2019 The Royal Society of Chemistry., MIT-Imperial College London MISTI Global Seed Fund, U.S. Defense Advanced Research Projects Agency’s Living Foundries program (award no. HR0011-15-C-0084), EPSRC (EP/K038648/1), EPSRC (EP/R013764/1)

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. To overcome these challenges, a coassembly of the M13 virus, cyanine 3 dye, and silver nanoparticles is developed to create a fluorescent tag capable of binding with molecular precision with high emissivity. Enhanced emission of cyanine 3 of up to 24‐fold is achieved by varying nanoparticle size and particle‐fluorophore separation. In addition, it is found that the fluorescence enhancement increases with increasing dye surface density on the viral capsid. Finally, this highly fluorescent probe is applied for in vitro staining of E. coli . These results demonstrate an inexpensive framework for achieving tuned fluorescence enhancements. The methodology developed in this work is potentially amendable to fluorescent detection of a wide range of M13/cell combinations., Defense Advanced Research Projects Agency (Award HR0011-15-C-0084)

Near-infrared (NIR) emissive nanomaterials are desired for bioimaging and drug delivery applications due to the high tissue penetration depth of NIR light, enabling in vitro/ex vivo/in vivo fluorescence tracking. Considering the scarcity of NIR-fluorescing biocompatible nanostructures, we have for the first-time synthesized nanometer-sized reduced graphene oxide-derived graphene quantum dots (RGQDs) with NIR (950 nm) emission highly biocompatible in vitro with no preliminary toxic response in vivo. RGQDs are obtained in a high-yield (∼90%) top-down sodium hypochlorite/ultraviolet-driven synthetic process from non-emissive micron-sized reduced graphene oxide (RGO) flakes. This oxidation of RGO yields quantum dots with an average size of 3.54 ± 0.05 nm and a highly crystalline graphitic lattice structure with distinguishable lattice fringes. RGQDs exhibit excitation-independent emission in the visible and NIR-I region with a maximum NIR quantum yield of ∼7%. Unlike their parent material, RGQDs show substantial biocompatibility with ∼75%–80% cell viability up to high (1 mg ml−1) concentrations verified via both MTT and luminescence-based cytotoxicity assays. Tracked in vitro via their NIR fluorescence, RGQDs exhibit efficient internalization in HeLa cells maximized at 12 h with further anticipated excretion. In vivo, RGQDs introduced intravenously to NCr nude mice allow for fluorescence imaging in live sedated animals without the need in sacrificing those at imaging time points. Their distribution in spleen, kidneys, liver, and intestine assessed from NIR fluorescence in live mice, is further confirmed by excised organ analysis and microscopy of organ tissue slices. This outlines the potential of novel RGQDs as NIR imaging probes suitable for tracking therapeutic delivery in live animal models. A combination of smaller size, water-solubility, bright NIR emission, simple/scalable synthesis, and high biocompatibility gives RGQDs a critical advantage over a number of existing nanomaterials-based imaging platforms.

With the global rise in incidence of cancer and infectious diseases, there is a need for the development of techniques to diagnose, treat, and monitor these conditions. The ability to efficiently capture and isolate cells and other biomolecules from peripheral whole blood for downstream analyses is a necessary requirement. Graphene oxide (GO) is an attractive template nanomaterial for such biosensing applications. Favorable properties include its two-dimensional architecture and wide range of functionalization chemistries, offering significant potential to tailor affinity toward aromatic functional groups expressed in biomolecules of interest. However, a limitation of current techniques is that as-synthesized GO nanosheets are used directly in sensing applications, and the benefits of their structural modification on the device performance have remained unexplored. Here, we report a microfluidic-free, sensitive, planar device on treated GO substrates to enable quick and efficient capture of Class-II MHC-positive cells from murine whole blood. We achieve this by using a mild thermal annealing treatment on the GO substrates, which drives a phase transformation through oxygen clustering. Using a combination of experimental observations and MD simulations, we demonstrate that this process leads to improved reactivity and density of functionalization of cell capture agents, resulting in an enhanced cell capture efficiency of 92 ± 7% at room temperature, almost double the efficiency afforded by devices made using as-synthesized GO (54 ± 3%). Our work highlights a scalable, cost-effective, general approach to improve the functionalization of GO, which creates diverse opportunities for various next-generation device applications.

Fluorescence imaging in the second near-infrared window (NIR-II, 1,000-1,700 nm) features deep tissue penetration, reduced tissue scattering, and diminishing tissue autofluorescence. Here, NIR-II fluorescent probes, including down-conversion nanoparticles, quantum dots, single-walled carbon nanotubes, and organic dyes, are constructed into biocompatible nanoparticles using the layer-by-layer (LbL) platform due to its modular and versatile nature. The LbL platform has previously been demonstrated to enable incorporation of diagnostic agents, drugs, and nucleic acids such as siRNA while providing enhanced blood plasma half-life and tumor targeting. This work carries out head-to-head comparisons of currently available NIR-II probes with identical LbL coatings with regard to their biodistribution, pharmacokinetics, and toxicities. Overall, rare-earth-based down-conversion nanoparticles demonstrate optimal biological and optical performance and are evaluated as a diagnostic probe for high-grade serous ovarian cancer, typically diagnosed at late stage. Successful detection of orthotopic ovarian tumors is achieved by in vivo NIR-II imaging and confirmed by ex vivo microscopic imaging. Collectively, these results indicate that LbL-based NIR-II probes can serve as a promising theranostic platform to effectively and noninvasively monitor the progression and treatment of serous ovarian cancer.

Graphene has attracted interest for a number of applications ranging from electronics, optoelectronics to membrane-based technologies. The thermal reduction of chemically exfoliated graphene oxide (GO) sheets represents an important step for large-scale, solution-based graphene synthesis. Therefore, understanding the reduction process and being able to provide new handles to control the resulting sheet properties is highly desirable. Using atomistic calculations combined with experiments, we study and demonstrate the impact of one such new handle – oxygen clustering on the graphene basal plane – on the structural and electrical properties of reduced GO (rGO) structures. Our calculations reveal that the number of oxygen and carbon atoms removed from the graphene plane during reduction can be tuned depending on the degree of oxygen clustering, without altering the reduction temperature. Further, we demonstrate that rGO thin films with improved sheet resistance (up to 2-fold smaller) can be obtained by facilitating oxygen clustering prior to reduction. Overall, our results highlight that oxygen clustering serves as a useful handle in controlling the structural and electrical properties of the resulting rGO structures, and could be potentially useful toward the synthesis of electrodes, graphene quantum dots and for different graphene-based thin film applications.

Carbon nanomaterials offer remarkable properties including high durability, conductivity, and versatility in modification. Carbon nanotubes and graphene oxide also exhibit fluorescence in the near-infrared (NIR) making those attractive for bioimaging and drug delivery applications due to the high tissue penetration depth of the NIR emission. However, despite these remarkable properties, the biocompatibility and degradability of carbon-based platforms still rise some unfortunate controversy that hampers their clinical utilization. In order to address this, we specifically develop NIR-emissive graphene-based quantum dots with high biocompatibility. We explore both the bottom-up and the top-down synthetic approaches together with a variety of doping strategies that yield 2 – 5 nm quasi-spherical quantum dots with graphitic lattice structure observable in TEM. In the bottom-up glucosamine-based synthesis the most prominent NIR emission is observed from graphene quantum dots doped by nitrogen, sulfur or rare-earth metals exhibiting transitions in that spectral region. These GQDs decorated with oxygen-containing functional groups identified with the FTIR have high water solubility and offer efficient cell internalization in HeLa and MCF-7 cells maximized at 12 h. Few percent doping with rare earth metals or nitrogen/sulfur heteroatoms as verified by the EDX does not substantially contribute to the toxic profile of the formulation: doped GQDs exhibit high biocompatibility up to 1 – 2 mg/mL concentrations and degradation in cell culture at 36 h. Finally, these GQDs exhibit emission in the visible with quantum yields up to 60% and also in the NIR, which is utilized for in vitro fluorescence imaging in both spectral regions. Top-down synthesized GQDs are derived from graphitic materials via UV-assisted radical-based oxidation. Unlike their parent material, these few-layered GQDs containing oxygen addends are water-soluble and exhibit fluorescence in the visible and a wavelength-independent emission in the NIR with NIR quantum yields ranging from 1 to 8%. They are also biocompatible with cell viability over 80% with up to 1 mg/mL GQD concentrations and exhibit cellular internalization within several hours tracked with their NIR fluorescence excited by the 808 nm diode laser. The NIR imaging capabilities of both bottom-up and top-down synthesized GQDs are verified in vivo in live mouse models showing detectable fluorescence in spleen with some liver and kidney signal observed with 808 laser excitation through the tissues of live animals. Excised organs show NIR GQD emission from kidneys, liver, spleen and intestine with GQDs also detected in single organ slices indicating their location within the particular organ. As a result, we suggest that NIR-emissive biocompatible GQDs synthesized both via bottom-up and top-down approaches can be developed and utilized as imaging and, potentially, drug delivery agents both in vitro and in vivo in small animal models.

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. Here, we rationally assemble 1D biological templates into scalable, 3D structures to fabricate metal nanofoams with a variety of genetically programmable architectures and material chemistries. We demonstrate that nanofoam architecture can be modulated by manipulating viral assembly, specifically by editing the viral surface coat protein, as well as altering templating density. These architectures were retained over a broad range of compositions including monometallic and bi-metallic combinations of noble and transition metals of copper, nickel, cobalt, and gold. Phosphorous and boron incorporation was also explored. In addition to increasing the surface area over a factor of 50, as compared to the nanofoam's geometric footprint, this process also resulted in a decreased average crystal size and altered phase composition as compared to non-templated controls. Finally, templated hydrogels were deposited on the centimeter scale into an array of substrates as well as free standing foams, demonstrating the scalability and flexibility of this synthetic method towards device integration. As such, we anticipate that this method will provide a platform to better study the synergistic and de-coupled effects between nano-structure and composition for a variety of applications including energy storage, catalysis, and sensing.

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. These integrated features of DNA allow for temporally efficient cutting of SWNTs into desired lengths, thus expanding the availability of SWNTs for applications in the fields of nanoelectronics, nanomedicine, nanomaterials, and quantum physics, as well as in fundamental studies.

We investigate an energy-efficient synthesis that merges the bio-templated technique and solid-state reactions to produce nano-structured lithiated polyanions. With the aid of bio-templates based on an M13 virus, the thermal budget of an annealing process can be reduced, and the nano-structured characteristics of the precursors are preserved in the product. This method enables us to successfully prepare monoclinic LiMnBO3 with an average particle size of 20 nm in a 1 h annealing process, showing improved electrochemical properties compared with the conventionally synthesized one. Thus, we consider that this bio-facilitated method can open up an environmentally-friendly pathway to produce nano-structured electrode materials with an enhanced performance.

Peripheral blood can provide valuable information on an individual’s immune status. Cell-based assays typically target leukocytes and their products. Characterization of leukocytes from whole blood requires their separation from the far more numerous red blood cells.1 Current methods to classify leukocytes, such as recovery on antibody-coated beads or fluorescence-activated cell sorting require long sample preparation times and relatively large sample volumes.2 A simple method that enables the characterization of cells from a small peripheral whole blood sample could overcome limitations of current analytical techniques. We describe the development of a simple graphene oxide surface coated with single-domain antibody fragments. This format allows quick and efficient capture of distinct WBC subpopulations from small samples (∼30 μL) of whole blood in a geometry that does not require any specialized equipment such as cell sorters or microfluidic devices., National Science Council of Taiwan (Grant 102-2917-I-564-001-A1), Calouste Gulbenkian Foundation, Portuguese Science and Technology Foundation, Champalimaud Foundation, National Institutes of Health (U.S.)

One of the challenges for achieving efficient exciton transport in solar energy conversion systems is precise structural control of the light-harvesting building blocks. Here, we create a tunable material consisting of a connected chromophore network on an ordered biological virus template. Using genetic engineering, we establish a link between the inter-chromophoric distances and emerging transport properties. The combination of spectroscopy measurements and dynamic modelling enables us to elucidate quantum coherent and classical incoherent energy transport at room temperature. Through genetic modifications, we obtain a significant enhancement of exciton diffusion length of about 68% in an intermediate quantum-classical regime.

Mesoporous semiconducting networks exhibit advantageous photoelectrochemical properties. The M13 virus is a versatile biological scaffold that has been genetically engineered to organize various materials into nanowire (NW)-based mesoporous structures. In this study, high-aspect ratio titanium dioxide NWs are synthesized by utilizing M13 viruses as templates, and the NWs are assembled into semiconducting mesoporous networks with tunable structural properties. To understand the effects of different morphologies on the photovoltaic performance, the as-fabricated networks are employed as photoanodes in liquid-state dye-sensitized solar cells (DSCs). Compared with traditional nanoparticle-based photoanodes, the NW-based DSC photoanodes demonstrate much higher electron diffusion lengths while maintaining a comparable light harvesting capacity, thus leading to improved power conversion efficiencies. In addition, the NW-based semiconducting mesoporous thin films are able to load sufficient organolead iodide pero...

We provide a detailed scientific demonstration to prove that the comment from the Yi Wang group is false.

Conductive polymer hydrogels, which synergize the advantageous features of hydrogels and conductive materials, have been utilized in many electrochemical energy storage applications. Here, we introduce phytic acid as (1) a dispersing agent for pristine multi-walled carbon nanotubes (MWNTs) in aqueous solution containing aniline and as (2) a gelator to form polyaniline (PANI)-based hydrogels after polymerization. The PANI-based hydrogels exhibit nanowire-based mesoporous networks with high surface area and electrical conductivity. The nanostructured core (MWNT)–shell (PANI) hydrogels show an improvement on the electrical conductivity from 0.21 to 1.54 S cm[superscript −1] as the loading of MWNTs increases from 0 to 5.0 wt%. The conducting nanowire-based networks with MWNT loadings of 3.0 wt% in the hydrogel provide efficient electron transport pathways that exhibit a maximal specific capacity of 609 F g[superscript −1]. The scalable and facile synthesis demonstrates excellent electrochemical performance, rendering it attractive for sensing, energy conversion, and energy storage applications., Eni S.p.A. (Firm) (Eni-MIT Energy Fellowship), National Science Foundation (U.S.). Center for Chemical Innovation (CHE-1305124), United States. Army Research Office. Institute for Collaborative Biotechnologies, Natural Sciences and Engineering Research Council of Canada (Postgraduate Scholarship)

We harnessed the hygroscopic and biofluorescent behaviors of microbial cells to design sweat-responsive 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. Experimental characterization and mechanical modeling of the film were performed to guide the design of a wearable running suit and a fluorescent shoe prototype with bio-flaps that dynamically modulates ventilation in synergy with the body’s need for cooling.

Biocatalysis has grown rapidly in recent decades as a solution to the evolving demands of industrial chemical processes. Mounting environmental pressures and shifting supply chains underscore the need for novel chemical activities, while rapid biotechnological progress has greatly increased the utility of enzymatic methods. Enzymes, though capable of high catalytic efficiency and remarkable reaction selectivity, still suffer from relative instability, high costs of scaling, and functional inflexibility. Herein, we developed a biochemical platform for engineering de novo semisynthetic enzymes, functionally modular and widely stable, based on the M13 bacteriophage. The hydrolytic bacteriophage described in this paper catalyzes a range of carboxylic esters, is active from 25 to 80 °C, and demonstrates greater efficiency in DMSO than in water. The platform complements biocatalysts with characteristics of heterogeneous catalysis, yielding high-surface area, thermostable biochemical structures readily adaptable to reactions in myriad solvents. As the viral structure ensures semisynthetic enzymes remain linked to the genetic sequences responsible for catalysis, future work will tailor the biocatalysts to high-demand synthetic processes by evolving new activities, utilizing high-throughput screening technology and harnessing M13's multifunctionality.

Solitary fluorescent defects on single-walled carbon nanotubes (SWCNTs) have been shown to emit short-wave infrared (SWIR) single photons at room-temperature, enabling applications for quantum communication or cryptography. In addition, the new emission band at lower energy allows better resolution and contrast of in vivo images because lower scattering and lower autofluorescence can be achieved by shifting both excitation and emission into SWIR. A more reliable and scalable method for synthesizing fluorescent defects on SWCNTs is needed for translating from fundamental studies to practical applications. Here, we introduce a fast and reproducible method for creating oxygen-doped fluorescent defects on SWCNTs. The maximum intensity of the defect emission is reached within 40 secs, which is at least 24 times faster than reported values. The oxygen source is provided by the photo-dissociation of the hypochlorite ions and the doping occurs by direct attachment of the oxygen atom onto the SWCNT wall. This method produces minimum non-fluorescent defects, and more than 95% of the resulting SWCNTs contain fluorescent defects. We also built a high-throughput flow reactor to synthesize the O-doped SWCNTs at scale and used them for imaging vascular and lymphatic systems.

Physical characterization of nanoparticles is required for a wide range of applications. Nanomechanical resonators can quantify the mass of individual particles with detection limits down to a single atom in vacuum. However, applications are limited because performance is severely degraded in solution. Suspended micro- and nanochannel resonators have opened up the possibility of achieving vacuum-level precision for samples in the aqueous environment and a noise equivalent mass resolution of 27 attograms in 1-kHz bandwidth was previously achieved by Lee et al. [(2010) Nano Lett 10(7):2537-2542]. Here, we report on a series of advancements that have improved the resolution by more than 30-fold, to 0.85 attograms in the same bandwidth, approaching the thermomechanical noise limit and enabling precise quantification of particles down to 10 nm with a throughput of more than 18,000 particles per hour. We demonstrate the potential of this capability by comparing the mass distributions of exosomes produced by different cell types and by characterizing the yield of self-assembled DNA nanoparticle structures.

Organolead halide perovskite solar cells (PSCs) show great promise as a new large-scale and cost-competitive photovoltaic technology. Power conversion efficiencies over 15% to 19% have been achieved within 18 to 24 months of development, and thus perovskite materials have attracted great attention in photovoltaic research. However, the manufacture of PSCs raises environmental concerns regarding the over-production of raw lead ore, which has harmful health and ecological effects. Herein, we report an environmentally responsible process to fabricate efficient PSCs by reusing car batteries to simultaneously avoid the disposal of toxic battery materials and provide alternative, readily available lead sources for PSCs. Perovskite films, assembled using materials sourced from either recycled battery materials or high-purity commercial reagents, show the same material characteristics (i.e., crystallinity, morphology, optical absorption, and photoluminescence properties) and identical photovoltaic performance (i.e., photovoltaic parameters and resistances of electron recombination), indicating the practical feasibility of recycling car batteries for lead-based PSCs.

In this study, photocatalytically active perovskite strontium titanate (SrTiO3) nanowires are fabricated for the first time using genetically engineered AEEE-M13 phage and metal alkoxide precursors. One newly developed doping approach with an ammonia gas treatment efficiently produced strontium titanate nanowires, which split water and produce hydrogen under visible-light irradiation. The optical absorption of nitrogen-doped strontium titanate can be tuned by varying the processing conditions and lies in the visible spectrum range when treated at 625 °C–650 °C. The excellent hydrogen evolution rate of these nanomaterials is correlated with both optical absorption and nitrogen doping level.