Nanoengineered Light-Activatable Polybubbles for On-Demand Therapeutic Delivery.

Vaccine coverage is severely limited in developing countries due to inefficient protection of vaccine functionality as well as lack of patient compliance to receive the additional booster doses. Thus, there is an urgent need to design a thermostable vaccine delivery platform that also enables release of the bolus after predetermined time. Here, the formation of injectable and light-activatable polybubbles for vaccine delivery is reported. In vitro studies show that polybubbles enable delayed burst release, irrespective of cargo types, namely small molecule and antigen. The extracorporeal activation of polybubbles is achieved by incorporating near-infrared (NIR)-sensitive gold nanorods (AuNRs). Interestingly, light-activatable polybubbles can be used for on-demand burst release of cargo. In vitro, ex vivo, and in vivo studies demonstrate successful activation of AuNR-loaded polybubbles. Overall, the light-activatable polybubble technology can be used for on-demand delivery of various therapeutics including small molecule drugs, immunologically relevant protein, peptide antigens, and nucleic acids.

Decade-spanning high-precision terahertz frequency comb.

The generation and detection of a decade-spanning terahertz (THz) frequency comb is reported using two Ti:sapphire femtosecond laser oscillators and asynchronous optical sampling THz time-domain spectroscopy. The comb extends from 0.15 to 2.4 THz, with a tooth spacing of 80 MHz, a linewidth of 3.7 kHz, and a fractional precision of 1.8×10^{-9}. With time-domain detection of the comb, we measure three transitions of water vapor at 10 mTorr between 1-2 THz with an average Doppler-limited fractional accuracy of 6.1×10^{-8}. Significant improvements in bandwidth, resolution, and sensitivity are possible with existing technologies.

Inflatable penile prosthesis placement in Peyronie's disease: a review of surgical considerations, approaches, and maneuvers.

Peyronie's disease (PD) is a fibrotic disorder of the tunica albuginea that results in penile deformity and/or curvature. Patients usually present complaining of penile pain, shortening and deformity resulting in dissatisfaction with intercourse. Many patients with PD will present with concomitant erectile dysfunction (ED). This disease is a significant concern for patients as it impacts both sexual function and overall quality of life. While there are several interventions available for PD treatment, inflatable penile prosthesis (IPP) implantation is considered the gold standard approach for those with moderate to severe concomitant ED, refractory to medical therapy. The goal of treatment is to give a man a functionally straight erection. Placement of an IPP alone may achieve this. However, when curvature still exists, several adjunct procedures may be performed to include manual modeling, plication, plaque incision or excision and grafting. Additionally, advanced lengthening procedures may also be used. In this paper we will present a comprehensive review of the adjuvant straightening techniques that can be used during IPP placement in men with PD and refractory ED when curvature still exists. Patient selection is a key predictor of implant success, as is preoperative and postoperative management to optimize overall patient care and satisfaction. These topics along with the different surgical approaches to IPP insertion for PD will also be discussed, including the benefits and shortcomings of each. A flowchart to aid surgeons in their intraoperative decision making based on curvature characteristics and specific patient concerns is presented.

Using two-photon excitation to control bending motions in molecular-crystal nanorods.

Molecular-crystal nanorods composed of 9-anthracenecarboxylic acid can undergo reversible bending due to molecular-level geometry changes associated with the photodimerization of the molecules in the crystal lattice. The use of highly focused near-IR femtosecond laser pulses results in two-photon excitation of micrometer-scale regions and is used to induce transient bends at various locations along the length of a single 200-nm-diameter nanorod. Bending can be observed in nanorods with diameters as small as 35 nm, and translational motion of a single nanorod could be induced by sequential bending of longer segments. A kinetic model is presented that quantitatively describes the bending and relaxation dynamics of individual rods. The results of this work show that it is possible to use laser excitation conditions to control the location, rate, and magnitude of photodeformations in these nanorods. The ability to control the motion of these ultrasmall photomechanical structures may be useful for manipulating objects on the nanoscale.

Controlling and quantifying the stability of amino acid-based cargo within polymeric delivery systems.

In recent years, the rapid growth and availability of protein and peptide therapeutics has not only expanded the boundaries of modern science but has also revolutionized the practice of medicine today. The potential of such therapies, however, is greatly limited by the innate instabilities of proteins and peptides, which is further magnified during therapeutic formulation processing, transport, storage, and administration. In this paper, we will consider the unique stability challenges associated with protein/peptide polymeric delivery systems from an engineering approach oriented towards the quantification and modification of amino acid-based cargo stability. While a number of methods have been developed for the purposes of quantifying factors affecting protein and peptide stability, current measurement techniques remain largely limited in scope in regard to polymeric drug delivery systems. This paper will primarily describe the influence of water content, pH, and temperature on protein and peptide stability within polymer-based delivery systems. Moreover, we will review current instrumentation used to quantify factors affecting protein/peptide stability with respect to water content, pH, and temperature. Lastly, we will outline several recommendations to help guide future research efforts to develop methods more specific to quantifying protein/peptide stability within polymer-based delivery systems.

A decade-spanning high-resolution asynchronous optical sampling terahertz time-domain and frequency comb spectrometer.

We present the design and capabilities of a high-resolution, decade-spanning ASynchronous OPtical Sampling (ASOPS)-based TeraHertz Time-Domain Spectroscopy (THz-TDS) instrument. Our system employs dual mode-locked femtosecond Ti:Sapphire oscillators with repetition rates offset locked at 100 Hz via a Phase-Locked Loop (PLL) operating at the 60th harmonic of the ∼80 MHz oscillator repetition rates. The respective time delays of the individual laser pulses are scanned across a 12.5 ns window in a laboratory scan time of 10 ms, supporting a time delay resolution as fine as 15.6 fs. The repetition rate of the pump oscillator is synchronized to a Rb frequency standard via a PLL operating at the 12th harmonic of the oscillator repetition rate, achieving milliHertz (mHz) stability. We characterize the timing jitter of the system using an air-spaced etalon, an optical cross correlator, and the phase noise spectrum of the PLL. Spectroscopic applications of ASOPS-THz-TDS are demonstrated by measuring water vapor absorption lines from 0.55 to 3.35 THz and acetonitrile absorption lines from 0.13 to 1.39 THz in a short pathlength gas cell. With 70 min of data acquisition, a 50 dB signal-to-noise ratio is achieved. The achieved root-mean-square deviation is 14.6 MHz, with a mean deviation of 11.6 MHz, for the measured water line center frequencies as compared to the JPL molecular spectroscopy database. Further, with the same instrument and data acquisition hardware, we use the ability to control the repetition rate of the pump oscillator to enable THz frequency comb spectroscopy (THz-FCS). Here, a frequency comb with a tooth width of 5 MHz is generated and used to fully resolve the pure rotational spectrum of acetonitrile with Doppler-limited precision. The oscillator repetition rate stability achieved by our PLL lock circuits enables sub-MHz tooth width generation, if desired. This instrument provides unprecedented decade-spanning, tunable resolution, from 80 MHz down to sub-MHz, and heralds a new generation of gas-phase spectroscopic tools in the THz region.

The structure and function of quinones in biological solar energy transduction: a cyclic voltammetry, EPR, and hyperfine sub-level correlation (HYSCORE) spectroscopy study of model naphthoquinones.

Quinones function as electron transport cofactors in photosynthesis and cellular respiration. The versatility and functional diversity of quinones is primarily due to the diverse midpoint potentials that are tuned by the substituent effects and interactions with surrounding amino acid residues in the binding site in the protein. In the present study, a library of substituted 1,4-naphthoquinones are analyzed by cyclic voltammetry in both protic and aprotic solvents to determine effects of substituent groups and hydrogen bonds on the midpoint potential. We use continuous-wave electron paramagnetic resonance (EPR) spectroscopy to determine the influence of substituent groups on the electronic properties of the 1,4-naphthoquinone models in an aprotic solvent. The results establish a correlation between the presence of substituent group(s) and the modification of electronic properties and a corresponding shift in the midpoint potential of the naphthoquinone models. Further, we use pulsed EPR spectroscopy to determine the effect of substituent groups on the strength and planarity of the hydrogen bonds of naphthoquinone models in a protic solvent. This study provides support for the tuning of the electronic properties of quinone cofactors by the influence of substituent groups and hydrogen bonding interactions.