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.

Near‐infrared (NIR) emitting biocompatible nanomaterials are desired in biotechnology as higher penetration depth fluorescence imaging probes. In this work, novel NIR‐emissive Nd3+‐doped or Tm3+‐doped biocompatible graphene quantum dots (GQDs) are developed via scalable, single‐step bottom‐up synthesis. Water‐soluble Nd‐GQDs/Tm‐GQDs with average diameters of 5.6–8.2 nm possess crystalline graphene lattice with <1 atomic percent of Nd/Tm and exhibit NIR fluorescence at ≈1060/≈925 nm attributed to the intrinsic transitions of Nd3+/Tm3+. High biocompatibility with >80% cell viability at 1 mg mL−1 for Nd‐GQDs and 0.25 mg mL−1 for Tm‐GQDs makes them well‐suited for bioimaging. In vitro, both GQD types exhibit efficient internalization with their intracellular emission maximized at 6 h. The pH‐dependence of this emission can serve as plethora of diagnostic applications. GQDs enable in vivo NIR imaging in live sedated NCr nude mice with IV administration: their NIR emission maximized at 6 h post‐injection is primarily detected in intestine, kidneys, liver, and spleen, however, diminishing to none at 48 h. Ex vivo organ/slice imaging shows significant Tm‐GQD fluorescence signatures in the aforementioned organs/slices. This capability of NIR fluorescence imaging in cells, tissues, and real‐time detection in live animals makes biocompatible rare‐earth metal‐doped GQDs an attractive new candidate for in vitro/in vivo/ex vivo theranostics.

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.

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 “inho” circular single-stranded DNA (cssDNA) gene packaging system, we produced miniature chlorotoxin inho (CTX-inho) 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-inho phage accumulated in brain tumors, facilitating shortwave infrared detection. Furthermore, we show that our inho phage can carry cssDNA that are transcriptionally active when delivered to GBM22 glioma cells in vitro. The ability to modulate the capsid display, surface loading, phage length, and cssDNA gene content makes the recombinant M13 phage particle an ideal delivery platform.

Aerogels are ultralight porous materials whose matrix structure can be formed by interlinking 880 nm long M13 phage particles. In theory, changing the phage properties would alter the aerogel matrix, but attempting this using the current production system leads to heterogeneous lengths. A phagemid system that yields a narrow length distribution that can be tuned in 0.3 nm increments from 50 to 2500 nm is designed and, independently, the persistence length varies from 14 to 68 nm by mutating the coat protein. A robotic workflow that automates each step from DNA construction to aerogel synthesis is used to build 1200 aerogels. This is applied to compare Ni-MnO x cathodes built using different matrixes, revealing a pareto-optimal relationship between performance metrics. This work demonstrates the application of genetic engineering to create "tuning knobs" to sweep through material parameter space; in this case, toward creating a physically strong and high-capacity battery.

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Current standard of care treatment for gliomas includes maximal safe surgical resection followed by concurrent chemoradiation, however, the diffuse infiltrative nature of gliomas present certain challenges for neurosurgeons to clearly visualize tumor tissue under conventional white light during microsurgical resection. Fluorescence-guided surgical techniques have been recently introduced to help surgeons better visualize tumor tissue under the operating microscope. Fluorescent dyes conjugated to nanoscale materials that are functionalized with glioma-targeting peptide sequences, such as the 39 amino acid chlorotoxin (CTX) peptide sequence, have demonstrated clinical efficacy in recognizing microscopic tumor cells during surgeries. M13 bacteriophage (phage) are versatile, genetically tunable nanocarriers that have been recently adapted for use as theranostic platforms. Applying p3 capsid CTX fusion with a unique “inho” circular single-stranded DNA (cssDNA) gene packaging system, we produced miniature CTX inho (CTX-inho phage particles with a minimum length of 50 nm that can target intracranial orthotopic patient-derived glioblastoma tumors in the brains of mice. Systemically-administered indocyanine green-conjugated CTX-inho phage accumulated in brain tumors, facilitating short-wave infrared detection. Furthermore, we show that our inho phage can carry cssDNA that are transcriptionally active when delivered to GBM22 glioma cells in vitro. The ability to modulate the capsid display, surface loading, phage length, and cssDNA gene content makes the recombinant M13 phage particle an ideal nanotheranostic platform for neuro-oncological applications.