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Hybrid nanostructures are promising for ultrasound-triggered drug delivery and treatment, called sonotheranostics. Structures based on plasmonic nanoparticles for photothermal-induced microbubble inflation for ultrasound imaging exist. However, they have limited therapeutic applications because of short microbubble lifetimes and limited contrast. Photochemistry-based sonotheranostics is an attractive alternative, but building near-infrared (NIR)-responsive echogenic nanostructures for deep tissue applications is challenging because photolysis requires high-energy (UV–visible) photons. Here, we report a photochemistry-based echogenic nanoparticle for in situNIR-controlled ultrasound imaging and ultrasound-mediated drug delivery. Our nanoparticle has an upconversion nanoparticle core and an organic shell carrying gas generator molecules and drugs. The core converts low-energy NIR photons into ultraviolet emission for photolysis of the gas generator. Carbon dioxide gases generated in the tumor-penetrated nanoparticle inflate into microbubbles for sonotheranostics. Using different NIR laser power allows dual-modal upconversion luminescence planar imaging and cross-sectional ultrasonography. Low-frequency (10 MHz) ultrasound stimulated microbubble collapse, releasing drugs deep inside the tumor through cavitation-induced transport. We believe that the photoechogenic inflatable hierarchical nanostructure approach introduced here can have broad applications for image-guided multimodal theranostics.

In-depth studies of nonradiative (NR) decay, seeking to maximize NR decay rate or manipulate other NR decay channels, are of greatest significance for improving the photothermal conversion efficiency (η) of organic materials for phototheranostics; however, to date, relevant work remains scarce. Here, we present an insightful study of NR decay in BODIPY (BDP) dye, in an aggregated state, i.e., in BDP nanoparticles (BDP NPs), which show an efficient additional NR decay channel from the aggregation-stabilized intermolecular charge transfer (CT) state, resulting in exceptionally high η (61%) for highly efficient phototheranostics in vivo. BDP NPs exhibit two ultrafast NR decay channels with ultrashort lifetimes of 1.7 and 50 ps, which is in stark contrast to the only S1→ S0NR channel with a long lifetime of 373 ps in the isolated BDP dye. More importantly, the ultrafast NR channel (1.7 ps) in BDP NPs depletes a substantial portion of the excited-state population (71%), which accounts for its much better photothermal effect as compared with the isolated BDP dye. Finally, BDP NPs display a highly efficient photoacoustic imaging (PAI) guided photothermal therapy (PTT) of tumors in live mice. This study presents a deeper fundamental understanding of NR decay in organic materials, setting a valuable guideline that may be widely applicable to similar molecular structure to develop more advanced organic materials not only for photothermal-related applications.

Magnetite (Fe3O4) nanocrystals (MNCs) are among the most-studied magnetic nanomaterials, and many reports of solution-phase synthesis of monodisperse MNCs have been published. However, lack of reproducibility of MNC synthesis is a persistent problem, and the keys to producing monodisperse MNCs remain elusive. Here, we define and explore synthesis parameters in this system thoroughly to reveal their effects on the product MNCs. We demonstrate the essential role of benzaldehyde and benzyl benzoate produced by oxidation of benzyl ether, the solvent typically used for MNC synthesis, in producing monodisperse MNCs. This insight allowed us to develop stable formulas for producing monodisperse MNCs and propose a model to rationalize MNC size and shape evolution. Solvent polarity controls the MNC size, while short ligands shift the morphology from octahedral to cubic. We demonstrate preparation of specific assemblies with these MNCs. This standardized and reproducible synthesis of MNCs of well-controlled size, shape, and magnetic properties demonstrates a rational approach to stabilizing and expanding existing protocols for nanocrystal syntheses and may drive practical advances including enhanced MRI contrast, higher catalytic selectivity, and more accurate magnetic targeting.

We introduce here a concept of remote photoinitiated reconfiguration of ligands adsorbed onto a nanocatalyst surface to enable reversible modulation of the catalytic activity. This is demonstrated by using peptide-ligand-capped Au nanoparticles with a photoswitchable azobenzene unit integrated into the biomolecular ligand. Optical switching of the azobenzene isomerization state drives rearrangement of the ligand layer, substantially changing the accessibility and subsequent catalytic activity of the underlying metal surface. The catalytic activity was probed using 4-nitrophenol reduction as a model reaction, where both the position of the photoswitch in the peptide sequence and its isomerization state affected the catalytic activity of the nanoparticles. Reversible switching of the isomerization state produces reversible changes in catalytic activity viareconfiguration of the biomolecular overlayer. These results provide a pathway to catalytic materials whose activity can be remotely modulated, which could be important for multistep chemical transformations that can be accessed viananoparticle-based catalytic systems.

Bionanocombinatorics is an emerging field that aims to use combinations of positionally encoded biomolecules and nanostructures to create materials and devices with unique properties or functions. The full potential of this new paradigm could be accessed by exploiting specific noncovalent interactions between diverse palettes of biomolecules and inorganic nanostructures. Advancement of this paradigm requires peptide sequences with desired binding characteristics that can be rationally designed, based upon fundamental, molecular-level understanding of biomolecule–inorganic nanoparticle interactions. Here, we introduce an integrated method for building this understanding using experimental measurements and advanced molecular simulation of the binding of peptide sequences to gold surfaces. From this integrated approach, the importance of entropically driven binding is quantitatively demonstrated, and the first design rules for creating both enthalpically and entropically driven nanomaterial-binding peptide sequences are developed. The approach presented here for gold is now being expanded in our laboratories to a range of inorganic nanomaterials and represents a key step toward establishing a bionanocombinatorics assembly paradigm based on noncovalent peptide-materials recognition.

Silicon nanocrystals can provide the outstanding imaging capabilities of toxic heavy-metal-based quantum dots without employing heavy metals and have potential for rapid progression to the clinic. Understanding the toxicity of silicon quantum dots (SiQDs) is essential to realizing this potential. However, existing studies of SiQD biocompatibility are limited, with no systematic progression from small-animal to large-animal studies that are more clinically relevant. Here, we test the response of both mice and monkeys to high intravenous doses of a nanoconstruct created using only SiQDs and FDA-approved materials. We show that (1) neither mice nor monkeys show overt signs of toxicity reflected in their behavior, body mass, or blood chemistry, even at a dose of 200 mg/kg. (2) This formulation did not biodegrade as expected. Elevated levels of silicon were present in the liver and spleen of mice three months post-treatment. (3) Histopathology three months after treatment showed adverse effects of the nanoformulation in the livers of mice, but showed no such effects in monkeys. This investigation reveals that the systemic reactions of the two animal models may have some differences and there are no signs of toxicity clearly attributable to silicon quantum dots.

We describe the development of novel and biocompatible core/shell (α-NaYbF4:Tm3+)/CaF2nanoparticles that exhibit highly efficient NIRin–NIRoutupconversion (UC) for high contrast and deep bioimaging. When excited at ∼980 nm, these nanoparticles emit photoluminescence (PL) peaked at ∼800 nm. The quantum yield of this UC PL under low power density excitation (∼0.3 W/cm2) is 0.6 ± 0.1%. This high UC PL efficiency is realized by suppressing surface quenching effects viaheteroepitaxial growth of a biocompatible CaF2shell, which results in a 35-fold increase in the intensity of UC PL from the core. Small-animal whole-body UC PL imaging with exceptional contrast (signal-to-background ratio of 310) is shown using BALB/c mice intravenously injected with aqueously dispersed nanoparticles (700 pmol/kg). High-contrast UC PL imaging of deep tissues is also demonstrated, using a nanoparticle-loaded synthetic fibrous mesh wrapped around rat femoral bone and a cuvette with nanoparticle aqueous dispersion covered with a 3.2 cm thick animal tissue (pork).

We have synthesized core/shell NaGdF4:Nd3+/NaGdF4nanocrystals with an average size of 15 nm and exceptionally high photoluminescence (PL) quantum yield. When excited at 740 nm, the nanocrystals manifest spectrally distinguished, near-infrared to near-infrared (NIR-to-NIR) downconversion PL peaked at ∼900, ∼1050, and ∼1300 nm. The absolute quantum yield of NIR-to-NIR PL reached 40% for core–shell nanoparticles dispersed in hexane. Time-resolved PL measurements revealed that this high quantum yield was achieved through suppression of nonradiative recombination originating from surface states and cross relaxations between dopants. NaGdF4:Nd3+/NaGdF4nanocrystals, synthesized in organic media, were further converted to be water-dispersible by eliminating the capping ligand of oleic acid. NIR-to-NIR PL bioimaging was demonstrated both in vitroand in vivothrough visualization of the NIR-to-NIR PL at ∼900 nm under incoherent lamp light excitation. The fact that both excitation and the PL of these nanocrystals are in the biological window of optical transparency, combined with their high quantum efficiency, spectral sharpness, and photostability, makes these nanocrystals extremely promising as optical biomaging probes.

Particle size is widely used to tune the electronic, optical, and catalytic properties of semiconductor nanocrystals. This contrasts with bulk semiconductors, where properties are tuned based on composition, either through doping or through band gap engineering of alloys. Ideally, one would like to control both size and composition of semiconductor nanocrystals. Here, we demonstrate production of silicon–germanium alloy nanoparticles by laser pyrolysis of silane and germane. We have used FTIR, TEM, XRD, EDX, SEM, and TOF-SIMS to conclusively determine their structure and composition. Moreover, we show that upon extended sonication in selected solvents, these bare nanocrystals can be stably dispersed without ligands, thereby providing the possibility of using them as an ink to make patterned films, free of organic surfactants, for device fabrication. The engineering of these SiGe alloy inks is an important step toward the low-cost fabrication of group IV nanocrystal optoelectronic, thermoelectric, and photovoltaic devices.

We report intense upconversion photoluminescence (PL) in colloidal LiYF4:Er3+nanocrystals under excitation with telecom-wavelength at 1490 nm. The intensities of two- and three-photon anti-Stokes upconversion PL bands are higher than or comparable to that of the Stokes emission under excitation with low power density in the range 5–120 W/cm2. The quantum yield of the upconversion PL was measured to be as high as ∼1.2 ± 0.1%, which is almost 4 times higher than the highest upconversion PL quantum yield reported to date for lanthanide-doped nanocrystals in 100 nm sized hexagonal NaYF4:Yb3+20%, Er3+2% using excitation at ∼980 nm. A power dependence study revealed that the intensities of all PL bands have linear dependence on the excitation power density, which was explained by saturation effects in the intermediate energy states.

In this study, we report the development of a nanoparticle-enhanced biosensor by integrating both the nanoparticles and immunoassay sensing technologies into a phase interrogation surface plasmon resonance (SPR) system for detecting antigen at a concentration as low as the femtomolar range. Our work has demonstrated that the plasmonic field extension generated from the gold film to gold nanorod (GNR) has led to a drastic sensitivity enhancement. Antibody-functionalized sensing film, together with antibody-conjugated GNRs, was readily served as a plasmonic coupling partner that can be used as a powerful ultrasensitive sandwich immunoassay for cancer-related disease detection. Experimentally, it was found that the bioconjugated GNR labels enhance the tumor necrosis factor alpha (TNF-α) antigen signal with more than 40-fold increase compared to the traditional SPR biosensing technique. The underlying principle was analyzed by simulating the near-field coupling between the sensing film and the GNR. The results have shown that GNRs were readily served as promising amplification labels in SPR sensing technology.

This article presents a new method for fabricating highly conductive gold nanostructures within a polymeric matrix with subwavelength resolution. The nanostructures are directly written in a gold precursor-doped photoresist using a femtosecond pulsed laser. The laser energy is absorbed by a two-photon dye, which induces simultaneous reduction of gold in the precursor and polymerization of the negative photoresist. This results in gold nanoparticle-doped polymeric lines that exhibit both plasmonic effects, due to the constituent gold nanoparticles, and relatively high conductivity (within an order of magnitude of the bulk metal), due to the high density of particles within these lines. Line widths from 150 to 1000 nm have been achieved with this method. Various optically functional structures have been prepared, and their structural and optical properties have been characterized. The influence of laser intensity and scan speed on feature size have been studied and found to be in agreement with predictions of a mathematical model of the process.

Quantum dots (QDs) have size-dependent optical properties that make them uniquely advantageous for in vivotargeted fluorescence imaging, traceable delivery, and therapy. The use of group II−VI (e.g., CdSe) QDs for these applications is advancing rapidly. However, group II−VI QDs contain toxic heavy metals that limit their in vivoapplications. Thus, replacing these with QDs of a biocompatible semiconductor, such as silicon (Si), is desirable. Here, we demonstrate that properly encapsulated biocompatible Si QDs can be used in multiple cancer-related in vivoapplications, including tumor vasculature targeting, sentinel lymph node mapping, and multicolor NIR imaging in live mice. This work overcomes dispersibility and functionalization challenges to in vivoimaging with Si QDs through a unique nanoparticle synthesis, surface functionalization, PEGylated micelle encapsulation, and bioconjugation process that produces bright, targeted nanospheres with stable luminescence and long (>40 h) tumor accumulation time in vivo. Upon the basis of this demonstration, we anticipate that Si QDs can play an important role in more sophisticated in vivomodels, by alleviating QD toxicity concerns while maintaining the key advantages of QD-based imaging methods.

Luminescent silicon quantum dots (SiQDs) are gaining momentum in bioimaging applications, based on their unique combination of optical properties and biocompatibility. Here, we report the development of a multimodal probe that combines the optical properties of silicon quantum dots with the superparamagnetic properties of iron oxide nanoparticles to create biocompatible magnetofluorescent nanoprobes. Multiple nanoparticles of each type are coencapsulated within the hydrophobic core of biocompatible phospholipid−polyethyleneglycol (DSPE-PEG) micelles. The size distribution and composition of the magnetofluorescent nanoprobes were characterized by transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS). Enhanced cellular uptake of these probes in the presence of a magnetic field was demonstrated in vitro. Their luminescence stability in a prostate cancer tumor model microenvironment was demonstrated in vivo. This paves the way for multimodal silicon quantum-dot-based nanoplatforms for a variety of imaging and delivery applications.

Photoluminescent NaYF4:Yb3+/Tm3+nanocrystals are ideally suited for in vitroand in vivophotoluminescence (PL) bioimaging due to their virtue of near-infrared to near-infrared (NIR-to-NIR) upconversion (UC); they display PL with a peak at ∼800 nm if excited at ∼980 nm. Here, we report the synthesis of monodisperse NaYF4:Yb3+/Tm3+nanocrystals of ultrasmall size (7−10 nm) with high UC efficiency. The intensity of their NIR UC emission was demonstrated to increase by up to 43 times along with an increase in the relative content of Yb3+ions from 20 to 100%, with a corresponding decrease in the Y3+content from 80 to 0%. The achieved ultrasmall NaYbF4:2% Tm3+nanocrystals manifest NIR PL emission, which is 3.6 times more intense than that from 25−30 nm sized NaYF4:20% Yb3+/2% Tm3+nanocrystals, previously synthesized and used for in vitroand in vivobioimaging. An optimization of both size and UC PL efficiency of NIR-to-NIR nanocrystals provides us with highly efficient optical imaging probes for bioapplications.

Successful translation of the use of nanoparticles from laboratories to clinics requires exhaustive and elaborate studies involving the biodistribution, clearance, and biocompatibility of nanoparticles for in vivobiomedical applications. We report here the use of multimodal organically modified silica (ORMOSIL) nanoparticles for in vivobioimaging, biodistribution, clearance, and toxicity studies. We have synthesized ORMOSIL nanoparticles with diameters of 20−25 nm, conjugated with near-infrared (NIR) fluorophores and radiolabeled them with 124I, for optical and PET imaging in vivo. The biodistribution of the nontargeted nanoparticles was studied in nontumored nude mice by optical fluorescence imaging, as well by measuring the radioactivity from harvested organs. Biodistribution studies showed a greater accumulation of nanoparticles in liver, spleen, and stomach than in kidney, heart, and lungs. The clearance studies carried out over a period of 15 days indicated hepatobiliary excretion of the nanoparticles. Selected tissues were analyzed for any potential toxicity by histological analysis, which confirmed the absence of any adverse effect or any other abnormalities in the tissues. The results demonstrate that these multimodal nanoparticles have potentially ideal attributes for use as biocompatible probes for in vivoimaging.

In this paper, we report the successful use of non-cadmium-based quantum dots (QDs) as highly efficient and nontoxic optical probes for imaging live pancreatic cancer cells. Indium phosphide (core)−zinc sulfide (shell), or InP/ZnS, QDs with high quality and bright luminescence were prepared by a hot colloidal synthesis method in nonaqueous media. The surfaces of these QDs were then functionalized with mercaptosuccinic acid to make them highly dispersible in aqueous media. Further bioconjugation with pancreatic cancer specific monoclonal antibodies, such as anticlaudin 4 and antiprostate stem cell antigen (anti-PSCA), to the functionalized InP/ZnS QDs, allowed specific in vitrotargeting of pancreatic cancer cell lines (both immortalized and low passage ones). The receptor-mediated delivery of the bioconjugates was further confirmed by the observation of poor in vitrotargeting in nonpancreatic cancer based cell lines which are negative for the claudin-4-receptor. These observations suggest the immense potential of InP/ZnS QDs as non-cadmium-based safe and efficient optical imaging nanoprobes in diagnostic imaging, particularly for early detection of cancer.