Hair loss is a prevalent dermatological disorder that significantly affects quality of life. Among FDA approved treatments, topically applied minoxidil is commonly used. Nevertheless, its low water solubility necessitates use of irritating solvents which hinder its clinical administration. Since these solvents usually cause adverse reactions, nanotechnology-based carriers have emerged as promising strategies for topical delivery of minoxidil. Thus, we prepared topical delivery nanocarriers, i.e., chitosan-coated nanocapsules (ChiNCs), to increase percutaneous delivery through intrinsic characteristics of chitosan and to increase encapsulation of minoxidil into the nanocarriers. ChiNCs were prepared through simple nanoprecipitation and encapsulated in high amounts of minoxidil. The minoxidil-loaded ChiNCs (MXD@ChiNCs) were evaluated for their physicochemical characteristics, colloidal stability, release profile, skin penetration, cytotoxicity, proliferation, hair growth via animal, and histological analyses. MXD@ChiNCs were successfully loaded with 50 wt.

Testosterone (TES) is converted to dihydrotestosterone (DHT), which can cause androgenic alopecia (AGA) because of an excessive reaction to TES. A 5-alpha reductase inhibitor is required to alleviate or manage AGA, inhibiting the conversion of TES to DHT. Finasteride (FINA) is a 5-alpha reductase inhibitor, FDA-approved for oral administration in alopecia treatment. Oral FINA administration causes systemic adverse effects; therefore, an alternative FINA delivery system is required. We aimed to develop a topical delivery formulation of FINA by incorporating HPCD-enhanced solubilization into chitosan nanocapsules (FINA@HCNCs), providing enhanced solubility, drug encapsulation, and skin permeability through intrinsic chitosan characteristics, all without penetration enhancer use. FINA@HCNCs demonstrated long-term stability (4 weeks) under physiological conditions and resuspensibility after lyophilization without the use of cryoprotectants. FINA from FINA@HCNCs exhibited sustained release, improving skin permeability compared to commercial products (Finjuve (R)). In vitro cell experiments revealed HCNC nontoxicity in three cell lines relevant to hair regeneration, and the proliferative effect of FINA@HCNCs improved. FINA@HCNCs induced superior anti-TES activity in dermal papilla cells. In vivo evaluation revealed that topical FINA@HCNCs significantly improved therapeutic efficacy compared to FINA, with FINA@HCNCs containing half the FINA dosage, but achieving comparable results. FINA@HCNCs are a novel topical skin-permeable FINA formulation for AGA treatment.

We investigated the role of dichloro-squaraine (SQ) dye aggregates in facilitating thymine-thymine interstrand photo-crosslinking within double crossover (DX) tiles, to develop thermally stable and structurally uniform two-dimensional (2D) DNA-based nanostructures. By strategically incorporating SQ modified thymine pairs, we enabled site-selective [2 + 2] photocycloaddition under 310 nm UV light. Strong dye-dye interactions, particularly through the formation of aggregates, facilitated covalent bond formation between proximal thymines. To evaluate the impact of dye aggregation on crosslinking efficiency, ten DX tile variants with varying SQ-modified thymine positions were tested. Our results demonstrated that SQ dye aggregates significantly enhanced crosslinking, driven by precise SQ-modified thymine dimer placement within the DNA tiles. Analytical techniques, including denaturing PAGE and UV-visible spectroscopy, validated successful crosslinking in DNA tiles with multiple SQ-modified thymine pairs. This non-phototoxic method offers a potential route for creating thermally stable, homogeneous higher-order DNA-dye assemblies with potential applications in photoactive and exciton-based fields such as optoelectronics, nanoscale computing, and quantum computing. The insights from this study establish a foundation for further exploration of advanced DNA-dye systems, enabling the design of next-generation DNA nanostructures with enhanced functional properties.

Packing conformations of molecular aggregates are known to strongly influence the locations and intensities of spectral peaks. Here, we develop the third-order nonlinear spectroscopy signals for a purely electronic model of a molecular dimer, which is a prototype aggregate system. The model-which focuses on excited-state absorption (ESA) pathways in two-dimensional electronic spectra-reveals that orientational averaging leads to diagnostic ESA peak locations for H- and J-dimers. We constructed DNA-templated dimers of cyanine molecules as representative systems and used ultrabroadband two-dimensional electronic spectroscopy measurements to support the predicted signatures arising from the theoretical model. Fitting of steady-state spectra supports the assigned packing conformations. The results elucidate how ESA peaks can be diagnostic spectral signatures of packing conformation. This work lays the foundation for future studies that can include the complicating effects of vibronic states and additional electronic levels.

Atopic dermatitis (AD) is a chronic cutaneous disease with a complex underlying mechanism, and it cannot be completely cured. Thus, most treatment strategies for AD aim at relieving the symptoms. Although corticosteroids are topically applied to alleviate AD, adverse side effects frequently lead to the withdrawal of AD therapy. Tacrolimus (TAC), a calcineurin inhibitor, has been used to treat AD, but its high molecular weight and insolubility in water hinder its skin permeability. Herein, we developed and optimized TAC-loaded chitosan-based nanoparticles (TAC@CNPs) to improve the skin permeability of TAC by breaking the tight junctions in the skin. The prepared nanoparticles were highly loadable and efficient and exhibited appropriate characteristics for percutaneous drug delivery. TAC@CNP was stable for 4 weeks under physiological conditions. CNP released TAC in a controlled manner, with enhanced skin penetration observed. In vitro experiments showed that CNP was nontoxic to keratinocyte (HaCaT) cells, and TAC@CNP dispersed in an aqueous solution was as anti-proliferative as TAC solubilized in a good organic solvent. Importantly, an in vivo AD mouse model revealed that topical TAC@CNP containing similar to 1/10 of the dose of TAC found in commercially used Protopic (R) Ointment exhibited similar anti-inflammatory activity to that of the commercial product. TAC@CNP represents a potential therapeutic strategy for the management of AD.

Accurate localization of partial electrical discharges is essential for the diagnosis of high-voltage systems. The current study achieves this by employing an acoustic sensor array and a beamforming approach. The occurrence of a partial discharge is accompanied by the emission of high-frequency sounds in the ultrasonic range, making localization a challenging task requiring many sensors to avoid spatial aliasing. Compressive frequency-difference beamforming, as previously proposed, can be effective in addressing this issue. We expand the method to include near-field localization by utilizing a spherical wave and propose a two-step normalization process. This eliminates the bias associated with nonplanar waves and standardizes the field variables, thereby preserving only the phase and relative amplitude information. A distributed algorithm based on the alternating direction multiplier method is used to solve the associated convex optimization problem. The proposed method is demonstrated using simulated and experimental data.

Molecular (dye) aggregates play a prominent role in light harvesting and are of interest in quantum information science; however, there are limited reports that programmably assemble many (>4) dye aggregates featuring strong coupling and exciton delocalization. Using oligonucleotides with four Cy5s covalently linked in series along the phosphate backbone, we bring 4, 8, and 16 Cy5s in close proximity by assembling four-armed junctions. We elucidate their structure via gel electrophoresis and steady-state and transient optical spectroscopy. We find that Cy5 has a strong propensity to form tetramer clusters, where the exciton is delocalized over all 4 Cy5s, that the exciton is not delocalized beyond tetramer clusters in the 8 and 16 Cy5 constructs, and that the 16 Cy5 construct may consist of pairs of tetramer clusters that are isolated from one another. Many-dye aggregates such as these may serve useful as antennae for their intense light absorption and spatially directed energy transfer.

We studied the exciton delocalization of indodicarbocyanine 5 dye derivative (Cy5-R) heterodimers templated by a DNA Holliday junction (HJ), which was quantified by the exciton hopping parameter Jm,n. These dyes were modified at the 5 and 5 ' positions of indole rings with substituent (R) H, Cl, tBu, Peg, and hexyloxy (Hex) groups that exhibit different bulkiness and electron-withdrawing/donating capacities. The substituents tune the physical properties of the dyes, such as hydrophobicity (log P) and solvent-accessible surface area (SASA). We tuned the Jm,n of heterodimers by attaching two Cy5-Rs in adjacent and transverse positions along the DNA-HJ. Adjacent heterodimers exhibited smaller Jm,n compared to transverse heterodimers, and some adjacent heterodimers displayed a mixture of H- and J-like aggregates. Most heterodimers exhibited Jm,n values within the ranges of the corresponding homodimers, but some heterodimers displayed synergistic exciton delocalization that resulted in larger Jm,n compared to their homodimers. We then investigated how chemically distinct Cy5-R conjugated to DNA can interact to create delocalized excitons. We determined that heterodimers involving Cy5-H and Cy5-Cl and a dye with larger substituents (bulky substituents and large SASA) such as Cy5-Peg, Cy5-Hex, and Cy5-tBu resulted in larger Jm,n. The combination provides steric hindrance that optimizes co-facial packing (bulky Cy5-R) with a smaller footprint (small SASA) that maximizes proximity. The results of this study lay a groundwork for rationally optimizing the exciton delocalization in dye aggregates for developing next-generation technologies based on optimized exciton transfer efficiency such as quantum information systems and biomedicine. We studied the exciton delocalization of indodicarbocyanine 5 dye derivative (Cy5-R) heterodimers templated by a DNA Holliday junction (HJ), which was quantified by the exciton hopping parameter Jm,n.

A bacteriochlorophyll a (Bchla) dimer is a basic functional unit in the LH1 and LH2 photosynthetic pigment-protein antenna complexes of purple bacteria, where an ordered, close arrangement of Bchla pigments-secured by noncovalent bonding to a protein template-enables exciton delocalization at room temperature. Stable and tunable synthetic analogs of this key photosynthetic subunit could lead to facile engineering of exciton-based systems such as in artificial photosynthesis, organic optoelectronics, and molecular quantum computing. Here, using a combination of synthesis and theory, we demonstrate that exciton delocalization can be achieved in a dimer of a synthetic bacteriochlorin (BC) featuring stability, high structural modularity, and spectral properties advantageous for exciton-based devices. The BC dimer was covalently templated by DNA, a stable and highly programmable scaffold. To achieve exciton delocalization in the absence of pigment-protein interactions critical for the Bchla dimer, we relied on the strong transition dipole moment in BC enabled by two auxochromes along the Qy transition, and omitting the central metal and isocyclic ring. The spectral properties of the synthetic "free" BC closely resembled those of Bchla in an organic solvent. Applying spectroscopic modeling, the exciton delocalization in the DNA-templated BC dimer was evaluated by extracting the excitonic hopping parameter, J to be 214 cm-1 (26.6 meV). For comparison, the same method applied to the natural protein-templated Bchla dimer yielded J of 286 cm-1 (35.5 meV). The smaller value of J in the BC dimer likely arose from the partial bacteriochlorin intercalation and the difference in medium effect between DNA and protein. We synthesized a de novo bacteriochlorin and created its dimer covalently attached to DNA. According to the spectral properties evaluated by modeling, the bacteriochlorin dimer showed exciton delocalization comparable to the natural Bchla dimer.

Biosensing using aptamers has been a recent interest for their versatility in detecting many different analytes across a wide range of applications, including medical and environmental applications. In our last work, we introduced a customizable aptamer transducer (AT) that could successfully feed-forward many different output domains to target a variety of reporters and amplification reaction networks. In this paper, we explore the kinetic behavior and performance of novel ATs by modifying the aptamer complementary element (ACE) chosen based on a technique for exploring the ligand-binding landscape of duplexed aptamers. Using published data, we selected and constructed several modified ATs that contain ACEs with varying length, position of the start sites, and position of single mismatches, whose kinetic responses were tracked with a simple fluorescence reporter. A kinetic model for ATs was derived and used to extract the strand-displacement reaction constant k1 and the effective aptamer dissociation constant Kd,eff, allowing us to calculate a relative performance metric, k1/Kd,eff. Comparing our results with the predictions based on the literature data, we provide useful insight into the dynamics of the adenosine AT's duplexed aptamer domain and suggest a high-throughput approach for future ATs to be developed with improved sensitivity. The performance of our ATs showed a moderate correlation to those predicted by the ACE scan method. Here, we find that predicted performance based on our ACE selection method was moderately correlated to our AT's performance.

DNA strand displacement networks are a critical part of dynamic DNA nanotechnology and are proven primitives for implementing chemical reaction networks. Precise kinetic control of these networks is important for their use in a range of applications. Among the better understood and widely leveraged kinetic properties of these networks are toehold sequence, length, composition, and location. While steric hindrance has been recognized as an important factor in such systems, a clear understanding of its impact and role is lacking. Here, a systematic investigation of steric hindrance within a DNA toehold-mediated strand displacement network was performed through tracking kinetic reactions of reporter complexes with incremental concatenation of steric moieties near the toehold. Two subsets of steric moieties were tested with systematic variation of structures and reaction conditions to isolate sterics from electrostatics. Thermodynamic and coarse-grained computational modeling was performed to gain further insight into the impacts of steric hindrance. Steric factors yielded up to 3 orders of magnitude decrease in the reaction rate constant. This pronounced effect demonstrates that steric moieties can be a powerful tool for kinetic control in strand displacement networks while also being more broadly informative of DNA structural assembly in both DNA-based therapeutic and diagnostic applications that possess elements of steric hindrance through DNA functionalization with an assortment of chemistries.

Aggregates of conjugated organic molecules (i.e., dyes) may exhibit relatively large one- and two-exciton interaction energies, which has motivated theoretical studies on their potential use in quantum information science (QIS). In practice, one way of realizing large one- and two-exciton interaction energies is by maximizing the transition dipole moment (μ) and difference static dipole moment (Δd) of the constituent dyes. In this work, we characterized the electronic structure and excited-state dynamics of monomers and aggregates of four asymmetric polymethine dyes templated via DNA. Using steady-state and time-resolved absorption and fluorescence spectroscopy along with quantum-chemical calculations, we found the asymmetric polymethine dye monomers exhibited a large μ, an appreciable Δd, and a long excited-state lifetime (τp). We formed dimers of all four dyes and observed that one dye, Dy 754, displayed the strongest propensity for aggregation and exciton delocalization. Motivated by these results, we undertook a more comprehensive survey of Dy 754 dimer and tetramer aggregates using steady-state absorption and circular dichroism spectroscopy. Modeling these spectra revealed an appreciable excitonic hopping parameter (J). Lastly, we used femtosecond transient absorption spectroscopy to characterize τp of the dimer and tetramer, which we observed to be exceedingly short. This work revealed that asymmetric polymethine dyes exhibited μ, Δd, monomer τp, and J values promising for QIS; however, further work is needed to overcome excited-state quenching and achieve long aggregate τp.

Molecular aggregates exhibit collective sharing of electronic excitation energy known as exciton delocalization, that can be leveraged in applications such as quantum computing, optical information processing, and light harvesting.

Programmable self-assembly of dyes using DNA templates to promote exciton delocalization in dye aggregates is gaining considerable interest. New methods to improve the rigidity of the DNA scaffold and thus the stability of the molecular dye aggregates to encourage exciton delocalization are desired. In these dye-DNA constructs, one potential way to increase the stability of the aggregates is to create an additional covalent bond via photo-cross-linking reactions between thymines in the DNA scaffold. Specifically, we report an approach to increase the yield of photo-cross-linking reaction between thymines in the core of a DNA Holliday junction while limiting the damage from UV irradiation to DNA. We investigated the effect of the distance between thymines on the photo-cross-linking reaction yields by using linkers with different lengths to tether the dyes to the DNA templates. By comprehensively evaluating the photo-cross-linking reaction yields of dye-DNA aggregates using linkers with different lengths, we conclude that interstrand thymines tend to photo-cross-link more efficiently with short linkers. A higher cross-linking yield was achieved due to the shorter intermolecular distance between thymines influenced by strong dye-dye interactions. Our method establishes the possibility of improving the stability of DNA-scaffolded dye aggregates, thereby expanding their use in exciton-based applications such as light harvesting, nanoscale computing, quantum computing, and optoelectronics.

Direction-of-arrival estimation is difficult for signals spatially undersampled by more than half the wavelength. Frequency-difference beamforming [Abadi, Song, and Dowling (2012). J. Acoust. Soc. Am. 132, 3018-3029] offers an alternative approach to avoid such spatial aliasing by using multifrequency signals and processing them at a lower frequency, the difference-frequency. As with the conventional beamforming method, lowering the processing frequency sacrifices spatial resolution due to a beam broadening. Thus, unconventional beamforming is detrimental to the ability to distinguish between closely spaced targets. To overcome spatial resolution deterioration, we propose a simple yet effective method by formulating the frequency-difference beamforming as a sparse signal reconstruction problem. Similar to compressive beamforming, the improvement (compressive frequency-difference beamforming) promotes sparse nonzero elements to obtain a sharp estimate of the spatial direction-of-arrival spectrum. Analysis of the resolution limit demonstrates that the proposed method outperforms the conventional frequency-difference beamforming in terms of separation if the signal-to-noise ratio exceeds 4 dB. Ocean data from the FAF06 experiment support the validity.

Molecular (dye) aggregates are a materials platform of interest in light harvesting, organic optoelectronics, and nanoscale computing, including quantum information science (QIS). Strong excitonic interactions between dyes are key to their use in QIS; critically, properties of the individual dyes govern the extent of these interactions. In this work, the electronic structure and excited-state dynamics of a series of indolenine-based squaraine dyes incorporating dimethylamino (electron donating) and/or nitro (electron withdrawing) substituents, so-called asymmetric dyes, were characterized. The dyes were covalently tethered to DNA Holliday junctions to suppress aggregation and permit characterization of their monomer photophysics. A combination of density functional theory and steady-state absorption spectroscopy shows that the difference static dipole moment (Δd) successively increases with the addition of these substituents while simultaneously maintaining a large transition dipole moment (μ). Steady-state fluorescence and time-resolved absorption and fluorescence spectroscopies uncover a significant nonradiative decay pathway in the asymmetrically substituted dyes that drastically reduces their excited-state lifetime (τ). This work indicates that Δd can indeed be increased by functionalizing dyes with electron donating and withdrawing substituents and that, in certain classes of dyes such as these asymmetric squaraines, strategies may be needed to ensure long τ, e.g., by rigidifying the π-conjugated network.

Retinyl palmitate (RP) is a retinol ester with strong antioxidant and anti-inflammatory properties as an antiwrinkle agent. However, it has poor aqueous solubility and easily degrades into inactive forms for topical applications. Therefore, we developed chitosan-coated nanocapsules (ChiNCs) to encapsulate RP using a simple nanoprecipitation method for protection against physiological conditions and to enable deep skin penetration. The as-prepared RP-loaded nanocapsules (RP@ChiNCs) loaded with approximately 5 wt.% RP exhibited a hydrodynamic diameter of 86 nm and surface charge of 24 mV. They had adequate stability to maintain their physicochemical properties after lyophilization in a biological buffer. Notably, ChiNCs provided RP with remarkable protection against degradation for 4 weeks at 37 °C. Thus, RP@ChiNCs exhibited good antioxidant activity in situ for sufficiently long periods without considerable changes in their efficacy. Furthermore, ChiNCs enhanced the skin penetration of lipophilic RP based on the inherent nature of chitosan. RP@ChiNCs exhibited good in vitro antioxidant and anti-inflammatory effects without causing any cytotoxicity in dermal fibroblasts. Accordingly, they promoted cell proliferation in a wound-scratch test and enhanced collagen synthesis. These results suggest that RP@ChiNCs are promising candidates for cosmetic and biomedical applications.

Understanding and controlling exciton coupling in dye aggregates has become a greater focus as potential applications such as coherent exciton devices, nanophotonics, and biosensing have been proposed. DNA nanostructure templates allow for a powerful modular approach. Using DNA Holliday junction (HJ) templates variations of dye combinations and precision dye positions can be rapidly assayed, as well as creating aggregates of dyes that could not be prepared (either due to excess or lack of solubility) through alternative means. Indodicarbocyanines (Cy5) have been studied in coupled systems due to their large transition dipole moment, which contributes to strong coupling. Cy5-R dyes were recently prepared by chemically modifying the 5,5 '-substituents of indole rings, resulting in varying dye hydrophobicity/hydrophilicity, steric considerations, and electron-donating/withdrawing character. We utilized Cy5-R dyes to examine the formation and properties of 30 unique DNA templated homodimers. We find that in our system the sterics of Cy5-R dyes play the determining factor in orientation and coupling strength of dimers, with coupling strengths ranging from 50-138 meV. The hydrophobic properties of the Cy5-R modify the percentage of dimers formed, and have a secondary role in determining the packing characteristics of the dimers when sterics are equivalent. Similar to other reports, we find that positioning of the Cy5-R within the HJ template can favor particular dimer interactions, specifically oblique or H-type dimers.