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Open Access Publications from the University of California

Scholarly Works (16 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2023)

Phenolic materials are naturally occurring molecules present in a wide range of organisms, from fungi to bacterium, and from plants to animals. Their unique structural and chemical features can form covalent or non-covalent interactions with diverse materials including inorganic (e.g., metal ion, metal oxide, silica, gold, silver), organic (e.g., small molecule, polymers), and biomaterials (e.g., proteins, peptides). As phenolic-based material can establish multiple physicochemical interactions such as metal coordination, hydrogen bonding, interactions, hydrophobic interactions, electrostatic interactions, and covalent bonding, diverse phenolic-enabled nanostructures have been developed for biomedical applications such as phenolic nanoparticles, phenolic surface coating, and secondary growth on phenolic surface. In this dissertation, I will explain how phenolic materials can benefit nanomaterials and their role in bioimaging and biosensing applications. First chapter reviews the hybrid gold nanorod-polydopamine nanoparticles which enhance photoacoustic performance more than bare gold nanorod both in in vitro and in vivo. The role of polydopamine shell in protection for gold nanorod is largely described. Second chapter describes the impact of nanoparticle size in photoacoustic and photothermal therapy. Two different-sized gold nanorods were synthesized and coated with polydopamine. These two different sizes of polydopamine-coated gold nanorod show same extinction peak (i.e., 1064 nm); however, the small size of gold nanorod exhibits remarkable photoacoustic and photothermal performance compared to large sized particles. Third chapter studies the polydopamine nanocapsule coated with organic dyes to detect heparin in whole human blood and plasma. The dye-coated polydopamine nanocapsule showed increased photoacoustic signal as a function of heparin concentration due to particle aggregation. In this chapter, tannic acid-mediated di thiol nanoparticles were also introduced to synthesize polydopamine nanocapsules. Fourth chapter investigates the impact of skin tone on biomedical optics. Darker skin tones (i.e., phototype) absorb and scatter more incident light before it reaches to target of interest. To understand the impact of skin tone, we mimic human skin using gelatin-based hydrogel and polydopamine nanoparticles (referred as synthetic melanin) in which they have similar chemical and optical properties compared to real melanin. Using 3D-bioprinted skin phantoms, multiple biomedical optics (photoacoustic, fluorescence, and photothermal) were extensively examined. Fifth chapter includes peptide-driven particle dissociation of gold nanoparticle aggregates for protease detection. Gold nanoparticle aggregation is often hindered by protein corona formation in biofluid, and undesired aggregation can produce false positives. In this chapter, diverse peptide structures were investigated for a matrix-insensitive dissociation platform.

    Cover page: Phenolic-enabled nanoparticle engineering for biomedical applications
    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2022)
    Synchronization is important for photoacoustic (PA) tomography, but some fixed delays between the data acquisition (DAQ) and the light pulse are a common problem degrading imaging quality. Here, we present a simple yet versatile method named Scissors to help synchronize ultrasound open platforms (UOPs) for PA imaging. Scissors is a programed function that can cut or add a fixed delay to radio frequency (RF) data and, thus, synchronize it before reconstruction. Scissors applies the programmable metric of UOPs and has several advantages. It is compatible with many setups regardless of the synchronization methods, light sources, transducers, and delays. The synchronization is adjustable in steps reciprocal to the UOPs sampling rate (20-ns step with a 50-MHz sampling rate). Scissors works in real-time PA imaging, and no extra hardware is needed. We programed Scissors in Vantage UOP (Verasonics, Inc., Kirkland, WA, USA) and then imaged two 30- [Formula: see text] nichrome wires with a 20.2-MHz central frequency transducer. The PA image was severely distorted by an 828-ns delay; over 90% delay was caused by our Q -switch laser. The axial and lateral resolutions are 112 and [Formula: see text], respectively, after using Scissors. We imaged a human finger in vivo, and the imaging quality is tremendously improved after solving the 828-ns delay by using Scissors.
      Cover page: Synchronization of RF Data in Ultrasound Open Platforms (UOPs) for High-Accuracy and High-Resolution Photoacoustic Tomography Using the Scissors Programming Method.
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2020)
      N95 decontamination protocols and KN95 respirators have been described as solutions to a lack of personal protective equipment. However, there are a few material science studies that characterize the charge distribution and physical changes accompanying disinfection treatments, particularly heating. Here, we report the filtration efficiency, dipole charge density, and fiber integrity of N95 and KN95 respirators before and after various decontamination methods. We found that the filter layers in N95 and KN95 respirators maintained their fiber integrity without any deformations during disinfection. The filter layers of N95 respirators were 8-fold thicker and had 2-fold higher dipole charge density than that of KN95 respirators. Emergency Use Authorization (EUA)-approved KN95 respirators showed filtration efficiencies as high as N95 respirators. Interestingly, although there was a significant drop in the dipole charge in both respirators during decontamination, there was no remarkable decrease in the filtration efficiencies due to mechanical filtration. Cotton and polyester face masks had a lower filtration efficiency and lower dipole charge. In conclusion, a loss of electrostatic charge does not directly correlate to the decreased performance of either respirator.
        Cover page: KN95 and N95 Respirators Retain Filtration Efficiency despite a Loss of Dipole Charge during Decontamination.
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2020)
        Personal protective equipment (PPE) including N95 respirators are critical for persons exposed to SARS-CoV-2. KN95 respirators and N95 decontamination protocols have been described as solutions to a lack of such PPE. However, there are a few materials science studies that characterize the charge distribution and physical changes accompanying disinfection treatments particularly heating. Here, we report the filtration efficiency, dipole charge density, and fiber integrity of pristine N95 and KN95 respirators before and after various decontamination methods. We found that the filter layer of N95 is 8-fold thicker than that of KN95, which explains its 10% higher filtration efficiency (97.03 %) versus KN95 (87.76 %) under pristines condition. After 60 minutes of 70 °C treatment, the filtration efficiency and dipole charge density of N95 became 97.16% and 12.48 µC/m2, while those of KN95 were 83.64% and 1.48 µC/m2 ; moreover, fit factor of N95 was 55 and that of KN95 was 2.7. In conclusion, the KN95 respirator is an inferior alternative of N95 respirator. In both systems, a loss of electrostatic charge does not directly correlate to a decrease in performance.
          Cover page: Assessment of N95 and K95 respirator decontamination: fiber integrity, filtration efficiency, and dipole charge density
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2023)
          Transmembrane protease serine 2 (TMPRSS2) is a plasma membrane protease that activates both spike protein of coronaviruses for cell entry and oncogenic signaling pathways for tumor progression. TMPRSS2 inhibition can reduce cancer invasion and metastasis and partially prevent the entry of SARS-CoV-2 into host cells. Thus, there is an urgent need for both TMPRSS2-selective imaging and precise screening of TMPRSS2 inhibitors. Here, we report a TMPRSS2-responsive surface-potential-tunable peptide-conjugated probe (EGTP) with aggregation-induced emission (AIE) features for TMPRSS2 selective imaging and accurate inhibitor screening. The amphiphilic EGTP was constructed with tunable surface potential and responsive efficiency with TMPRSS2 and its inhibitor. The rational construction of AIE luminogens (AIEgens) with modular peptides indicated that the cleavage of EGTP led to a gradual aggregation with bright fluorescence in high TMPRSS2-expressing cells. This strategy may have value for selective detection of cancer cells, SARS-CoV-2-target cells, and screening of protease inhibitors.
            Cover page: Protease-Responsive Potential-Tunable AIEgens for Cell Selective Imaging of TMPRSS2 and Accurate Inhibitor Screening.
            • Article
            • Peer Reviewed
            UC Berkeley Previously Published Works (2021)
            Phenolics are ubiquitous in nature and have gained immense research attention because of their unique physiochemical properties and widespread industrial use. In recent decades, their accessibility, versatile reactivity, and relative biocompatibility have catalysed research in phenolic-enabled nanotechnology (PEN) particularly for biomedical applications which have been a major benefactor of this emergence, as largely demonstrated by polydopamine and polyphenols. Therefore, it is imperative to overveiw the fundamental mechanisms and synthetic strategies of PEN for state-of-the-art biomedical applications and provide a timely and comprehensive summary. In this review, we will focus on the principles and strategies involved in PEN and summarize the use of the PEN synthetic toolkit for particle engineering and the bottom-up synthesis of nanohybrid materials. Specifically, we will discuss the attractive forces between phenolics and complementary structural motifs in confined particle systems to synthesize high-quality products with controllable size, shape, composition, as well as surface chemistry and function. Additionally, phenolic's numerous applications in biosensing, bioimaging, and disease treatment will be highlighted. This review aims to provide guidelines for new scientists in the field and serve as an up-to-date compilation of what has been achieved in this area, while offering expert perspectives on PEN's use in translational research.
              Cover page: Phenolic-enabled nanotechnology: versatile particle engineering for biomedicine
              • Article
              • Peer Reviewed
              UC San Diego Previously Published Works (2022)
              Heparin is a common anticoagulant, but heparin overdose is a common intensive care unit (ICU) medication error due to the narrow therapeutic window of heparin. Conventional methods to monitoring heparin suffer from long turnaround time, the need for skilled personnel, and low frequency of sampling. To overcome these issues, we describe here a fiber optic photoacoustic (PA) sensor for real-time heparin monitoring. The proposed sensor was validated with in vitro testing and in a simulated in vivo model using the following samples: (1) phosphate-buffered saline (PBS), (2) spiked human plasma, (3) spiked whole human blood, and (4) clinical samples from patients treated with heparin. Samples were validated by comparing the PA signal to the activated partial thromboplastin time (aPTT) as well as the activated clotting time (ACT). Importantly, the proposed sensor has a short turnaround time (3 min) and a limit of detection of 0.18 U/ml in whole human blood. The PA signal is linear with heparin dose and correlates with the aPTT value (Pearson's r = 0.99). The PA signal from 32 clinical samples collected from eight patients linearly correlated with ACT values (Pearson's r = 0.89, in vitro; Pearson's r = 0.93, simulated in vivo). The PA signal was also validated against the cumulative heparin dose (Pearson's r = 0.94, in vitro; Pearson's r = 0.96, simulated in vivo). This approach could have applications in both in vitro and real-time in vivo heparin monitoring.
                Cover page: A fiber optic photoacoustic sensor for real-time heparin monitoring
                • Article
                • Peer Reviewed
                UC San Diego Previously Published Works (2023)
                Noroviruses are highly contagious and are one of the leading causes of acute gastroenteritis worldwide. Due to a lack of effective antiviral therapies, there is a need to diagnose and surveil norovirus infections to implement quarantine protocols and prevent large outbreaks. Currently, the gold standard of diagnosis uses reverse transcription polymerase chain reaction (RT-PCR), but PCR can have limited availability. Here, we propose a combination of a tunable peptide substrate and gold nanoparticles (AuNPs) to colorimetrically detect the Southampton norovirus 3C-like protease (SV3CP), a key protease in viral replication. Careful design of the substrate employs a zwitterionic peptide with opposite charged moieties on the C- and N- termini to induce a rapid color change visible to the naked eye; thus, this color change is indicative of SV3CP activity. This work expands on existing zwitterionic peptide strategies for protease detection by systematically evaluating the effects of lysine and arginine on nanoparticle charge screening. We also determine a limit of detection for SV3CP of 28.0 nM with comparable results in external breath condensate, urine, and fecal matter for 100 nM of SV3CP. The key advantage of this system is its simplicity and accessibility, thus making it an attractive tool for qualitative point-of-care diagnostics.
                  Cover page: An approach to zwitterionic peptide design for colorimetric detection of the Southampton norovirus SV3CP protease.
                  • Article
                  • Peer Reviewed
                  UC San Diego Previously Published Works (2024)
                  Stability issues in membrane-free coacervates have been addressed with coating strategies, but these approaches often compromise the permeability of the coacervate. Here we report a facile approach to maintain both stability and permeability using tannic acid and then demonstrate the value of this approach in enzyme-triggered drug release. First, we develop size-tunable coacervates via self-assembly of heparin glycosaminoglycan with tyrosine and arginine-based peptides. A thrombin-recognition site within the peptide building block results in heparin release upon thrombin proteolysis. Notably, polyphenols are integrated within the nano-coacervates to improve stability in biofluids. Phenolic crosslinking at the liquid-liquid interface enables nano-coacervates to maintain exceptional structural integrity across various environments. We discover a pivotal polyphenol threshold for preserving enzymatic activity alongside enhanced stability. The disassembly rate of the nano-coacervates increases as a function of thrombin activity, thus preventing a coagulation cascade. This polyphenol-based approach not only improves stability but also opens the way for applications in biomedicine, protease sensing, and bio-responsive drug delivery.
                    Cover page: Polyphenol-stabilized coacervates for enzyme-triggered drug delivery.
                    • Article
                    • Peer Reviewed
                    UC San Diego Previously Published Works (2023)
                    3D-bioprinted skin-mimicking phantoms with skin colors ranging across the Fitzpatrick scale are reported. These tools can help understand the impact of skin phototypes on biomedical optics. Synthetic melanin nanoparticles of different sizes (70-500 nm) and clusters are fabricated to mimic the optical behavior of melanosome. The absorption coefficient and reduced scattering coefficient of the phantoms are comparable to real human skin. Further the melanin content and distribution in the phantoms versus real human skins are validated via photoacoustic (PA) imaging. The PA signal of the phantom can be improved by: 1) increasing melanin size (3-450-fold), 2) increasing clustering (2-10.5-fold), and 3) increasing concentration (1.3-8-fold). Then, multiple biomedical optics tools (e.g., PA, fluorescence imaging, and photothermal therapy) are used to understand the impact of skin tone on these modalities. These well-defined 3D-bioprinted phantoms may have value in translating biomedical optics and reducing racial bias.
                      Cover page: 3D‐Bioprinted Phantom with Human Skin Phototypes for Biomedical Optics
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