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Open Access Publications from the University of California

Scholarly Works (9 results)

  • Article
  • Peer Reviewed
UC San Diego Previously Published Works (2016)
Stem cell therapy (SCT) has shown very promising preclinical results in a variety of regenerative medicine applications. Nevertheless, the complete utility of this technology remains unrealized. Imaging is a potent tool used in multiple stages of SCT and this review describes the role that imaging plays in cell harvest, cell purification, and cell implantation, as well as a discussion of how imaging can be used to assess outcome in SCT. We close with some perspective on potential growth in the field.
    Cover page: Stem Cell Imaging: Tools to Improve Cell Delivery and Viability
    • Thesis
    • Peer Reviewed
    UC San Diego Electronic Theses and Dissertations (2019)

    Photoacoustic imaging uses nanosecond laser pulses to excite materials and generate acoustic waves. This “light in, sound out” technique can extend the applications of traditional ultrasound by harnessing the optical properties of materials. These features can be used for the non-invasive monitoring of drugs, molecular interaction, and diseases. In this dissertation, I will present three case studies that use photoacoustic imaging in tandem with nanoparticle contrast agents. The first case leverages photoacoustic imaging for heparin and clotting time monitoring via phenothiazine dyes embedded in nanomaterials. The heparin concentration and clotting time could be determined by the photoacoustic intensity of methylene blue increased by heparin, and this signal enhancement was due to the aggregation between the two molecules. To translate this technique for clinical use, we developed a cellulose sensor loaded with Nile blue A for finger-prick diagnostics. Human studies using 78 blood samples revealed that the photoacoustic intensity of the sensor was strongly correlated to the activated clotting time (Pearson’s r=0.86), which was the gold standard for clotting time measurement. In addition to direct measurements of therapeutic, the second study used photoacoustic imaging to monitor the micellization of sodium dodecyl sulfate (SDS). The micellization can be determined because the photoacoustic intensity of methylene blue shows 492-fold enhancement upon addition of 3.47 mM SDS due to fluorescent quenching, which is caused by the aggregation between methylene blue and SDS. Higher concentrations above the SDS critical micelle concentration at 8.67 mM decreases the intensity signal by 54-fold because of the disassociation of the aggregates. The final case evaluated copper sulfide (CuS) nanodisk and nanoprism as the photoacoustic contrast agents for ovarian tumor detection. We found that the nanodisks have 1.8-fold higher accumulation than nanoprisms in the ovarian tumors indicating the importance of nanoparticle shape for tumor penetration. Versus baseline, the tumors treated with nanodisk revealed three-fold stronger photoacoustic intensity with a characteristic intensity peak at 920 nm. These three photoacoustic applications could improve healthcare because photoacoustic imaging is faster and more cost-effective than most of the imaging modalities in medicine.

    • 3 supplemental videos
    Cover page: Photoacoustic Monitoring of Anticoagulant Therapy and Other Imaging Applications
    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2019)
    The preclinical landscape of photoacoustic imaging has experienced tremendous growth in the past decade. This non-invasive imaging modality augments the spatiotemporal capabilities of ultrasound with optical contrast. While it has principally been investigated for diagnostic applications, many recent reports have described theranostic delivery systems and drug monitoring strategies using photoacoustics. Here, we provide an overview of the progress to date while highlighting work in three specific areas: theranostic nanoparticles, real-time drug monitoring, and stem cell ("living drug") tracking. Additionally, we discuss the challenges that remain to be addressed in this burgeoning field.
      Cover page: Listening for the therapeutic window: Advances in drug delivery utilizing photoacoustic imaging
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2019)
      Transvaginal ultrasound is widely used for ovarian cancer screening but has a high false positive rate. Photoacoustic imaging provides additional optical contrast to supplement ultrasound and might be able to improve the accuracy of screening. Here, we report two copper sulfide (CuS) nanoparticles types (nanodisks and triangular nanoprisms) as the photoacoustic contrast agents for imaging ovarian cancer. Both CuS nanoprisms and nanodisks were ~6 nm thick and ~26 nm wide and were coated with poly(ethylene glycol) to make them colloidally stable in phosphate buffered saline (PBS) for at least 2 weeks. The CuS nanodisks and nanoprisms revealed strong localized surface plasmon resonances with peak maxima at 1145 nm and 1098 nm, respectively. Both nanoparticles types had strong and stable photoacoustic intensity with detection limits below 120 pM. The circular CuS nanodisk remained in the circulation of nude mice (n=4) and xenograft 2008 ovarian tumors (n=4) 17.9-fold and 1.8-fold more than the triangular nanoprisms, respectively. Finally, the photoacoustic intensity of the tumors from the mice (n=3) treated with CuS nanodisks was 3.0-fold higher than the baseline. The tumors treated with nanodisks had a characteristic peak at 920 nm in the spectrum to potentially differentiate the tumor from adjacent tissues.
        Cover page: Copper Sulfide Nanodisks and Nanoprisms for Photoacoustic Ovarian Tumor Imaging.
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2018)
        The personal ultraviolet (UV) dosimeter is a useful measurement tool to prevent UV induced dermal damages; however, conventional digital dosimeters are either bulky or require external power sources. Here, a wearable, colorimetric UV film dosimeter that provides color transition, from purple to transparent, is reported to indicate the UV dose. The film dosimeter is made of a purple photodegradable dye ((2Z,6Z)-2,6-bis(2-(2,6-diphenyl-4H-thiopyran-4-ylidene)ethylidene)cyclohexanone or DTEC) blended in low density polyethylene film. The DTEC film discolored 3.3 times more under the exposure of UV light (302 nm) than visible light (543 nm), and a UV bandpass filter is developed to increase this selectivity to UV light. The DTEC film completely discolors to transparency in 2 h under an AM 1.5 solar simulator, suggesting the potential as an indicator for individuals with types I-VI skin to predict interventions to avoid sunburn. Finally, the DTEC film is integrated with the UV bandpass filter on a wristband to function as a wearable dosimeter for low cost and convenient monitoring of sunlight exposure.
          Cover page: A Wearable Colorimetric Dosimeter to Monitor Sunlight Exposure
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2017)
          Ultrasound is critical in many areas of medicine including obstetrics, oncology, and cardiology with emerging applications in regenerative medicine. However, one critical limitation of ultrasound is the low contrast of target tissue over background. Here, we describe a novel cup-shaped silica nanoparticle that is reminiscent of exosomes and that has significant ultrasound impedance mismatch for labelling stem cells for regenerative medicine imaging. These exosome-like silica nanoparticles (ELS) were created through emulsion templating and the silica precursors bis(triethoxysilyl)ethane (BTSE) and bis(3-trimethoxysilyl-propyl)amine (TSPA). We found that 40% TSPA resulted in the exosome like-morphology and a positive charge suitable for labelling mesenchymal stem cells. We then compared this novel structure to other silica structures used in ultrasound including Stober silica nanoparticles (SSN), MCM-41 mesoporous silica nanoparticles (MSN), and mesocellular foam silica nanoparticles (MCF) and found that the ELS offered enhanced stem cell signal due to its positive charge to facilitate cell uptake as well as inherently increased echogenicity. The in vivo detection limits were <500 cells with no detectable toxicity at the concentrations used for labelling. This novel structure may eventually find utility in applications beyond imaging requiring an exosome-like shape including drug delivery.
            Cover page: Exosome-like silica nanoparticles: a novel ultrasound contrast agent for stem cell imaging
            • Article
            • Peer Reviewed
            UC San Diego Previously Published Works (2019)
            Contrast-enhanced ultrasound (CEUS) offers the exciting prospect of retaining the ease of ultrasound imaging while enhancing imaging clarity, diagnostic specificity, and theranostic capability. To advance the capabilities of CEUS, the synthesis and understanding of new ultrasound contrast agents (UCAs) is a necessity. Many UCAs are nano- or micro-scale materials composed of a perfluorocarbon (PFC) and stabilizer that synergistically induce an ultrasound response that is both information-rich and easily differentiated from natural tissue. In this work, we probe the extent to which CEUS is modulated through variation in a PFC stabilized with fluorine-modified polydopamine nanoparticles (PDA NPs). The high level of synthetic tunability in this system allows us to study signal as a function of particle aggregation and PFC volatility in a systematic manner. Separation of aggregated and non-aggregated nanoparticles lead to a fundamentally different signal response, and for this system, PFC volatility has little effect on CEUS intensity despite a range of over 50 °C in boiling point. To further explore the imaging tunability and multimodality, Fe3+-chelation was employed to generate an enhanced photoacoustic (PA) signal in addition to the US signal. In vitro and in vivo results demonstrate that PFC-loaded PDA NPs show stronger PA signal than the non-PFC ones, indicating that the PA signal can be used for in situ differentiation between PFC-loading levels. In sum, these data evince the rich role synthetic chemistry can play in guiding new directions of development for UCAs.
              Cover page: Tuning the ultrasonic and photoacoustic response of polydopamine-stabilized perfluorocarbon contrast agents
              • Article
              • Peer Reviewed
              LBL Publications (2023)
              Defect engineering has proven to be one of the most effective approaches for the design of high-performance electrocatalysts. Current methods to create defects typically follow a top-down strategy, cutting down the pristine materials into fragmented pieces with surface defects yet also heavily destroying the framework of materials that imposes restrictions on the further improvements in catalytic activity. Herein, we describe a bottom-up strategy to prepare free-standing NiFe layered double hydroxide (LDH) nanoplatelets with abundant internal defects by controlling their growth behavior in acidic conditions. Our best-performing nanoplatelets exhibited the lowest overpotential of 241 mV and the lowest Tafel slope of 43 mV/dec for the oxygen evolution reaction (OER) process, superior to the pristine LDHs and other reference cation-defective LDHs obtained by traditional etching methods. Using both material characterization and density functional theory (DFT) simulation has enabled us to develop relationships between the structure and electrochemical properties of these catalysts, suggesting that the enhanced electrocatalytic activity of nanoplatelets mainly results from their defect-abundant structure and stable layered framework with enhanced exposure of the (001) surface.
                Cover page: Intrabasal Plane Defect Formation in NiFe Layered Double Hydroxides Enabling Efficient Electrochemical Water Oxidation.
                • Article
                • Peer Reviewed
                UC San Diego Previously Published Works (2019)
                Heparin is an indispensable drug in anticoagulation therapy but with a narrow therapeutic window, which dictates regular testing and dose adjustment. However, current monitoring tools have a long turnaround time or are operator intensive. In this work, we describe a cellulose-based photoacoustic sensor for heparin. The sensors have a turnaround time of 6 min for whole blood samples and 3 min for plasma samples regardless of heparin concentration. These sensors have a limit of detection of 0.28 U/ml heparin in human plasma and 0.29 U/ml in whole blood with a linear response (Pearson's r = 0.99) from 0 to 2 U/ml heparin in plasma and blood samples. The relative standard deviation was < 12.5% in plasma and < 17.5% in whole blood. This approach was validated with heparin-spiked whole human blood and had a linear correlation with the activated partial thromboplastin time (aPTT) (r = 0.99). We then studied 16 sets of clinical samples-these had a linear correlation with the activated clotting time (ACT) (Pearson's r = 0.86, P < 0.0001). The photoacoustic signal was also validated against the cumulative heparin dose (Pearson's r = 0.71, P < 0.0001). This approach could have applications in bed-side heparin assays for continuous heparin monitoring.
                  Cover page: A cellulose-based photoacoustic sensor to measure heparin concentration and activity in human blood samples
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