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Open Access Publications from the University of California

Scholarly Works (10 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2025)

Protein therapeutics form a cornerstone of modern medicine, providing effective treatments for a wide range of conditions, including cancer, autoimmune diseases, and metabolic disorders. Despite their significant success, therapeutic proteins encounter substantial biological challenges, such as enzymatic degradation, rapid renal clearance, immune activation, limited cellular uptake, and difficulties in crossing critical barriers like the blood-brain barrier. Current delivery methods, such as subcutaneous and intravenous administration, inadequately address these obstacles, underscoring the need for advanced delivery platforms.Nanotechnology has emerged as a transformative approach to overcoming these challenges. Among nanocarriers, lipid-based nanoparticles, polymeric systems, protein-based carriers, virus-like particles, inorganic nanocarriers, and antibody-drug conjugates (ADCs) have demonstrated considerable promise, with several achieving FDA approval. However, significant limitations persist, including immunogenicity, stability issues, off-target effects, and high production costs. To address these challenges, our group has developed an innovative nanocapsule platform technology for protein therapeutic delivery. However, the potential of polymer-based protein nanocomplexes remains far from fully realized. In my dissertation, I aim to advance this field by focusing on two key objectives: 1.Development of coacervate-based protein nanocomplex for multi-enzyme cascade encapsulation and treatment for cancer starvation therapy 2.Design of virus-mimicking intracellular protein and gene delivery systems via direct cell-membrane penetration This versatile platform represents a customizable solution to overcoming biological barriers, enhancing therapeutic efficacy, and addressing persistent challenges in protein delivery. The proposed nanocomplex systems mark a significant step forward in advancing nanomedicine, with the potential to meet critical unmet medical needs and pave the way for future innovations in therapeutic delivery.

    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2025)
    Metabolic processes in living organisms depend on the synergistic actions of enzymes working in proximity and in concert, catalyzing reactions effectively while regulating the formation of metabolites. This enzyme synergy offers promising therapeutic application for diseases such as alcohol intoxication, cancer, and hyperinflammation. Despite their potential, the clinical translation of enzyme cascades is restricted by challenges including poor enzyme stability, short half-life, and a lack of delivery strategies that maintain enzyme proximity. In this study, multi-enzyme nanocascades synthesized are developed through in situ atom transfer radical polymerization using a zwitterionic monomer. This method markedly enhances enzyme stability and proximity, thereby prolonging their circulation half-life after systemic administration. It is demonstrated that the nanocascades of uricase and catalase effectively reduce uric acid levels without excessive hydrogen peroxide production, providing a potential antidote for hyperuricemia. Moreover, in a murine breast cancer model, the nanocascades of glucose oxidase and catalase inhibited tumor progression and enhanced the therapeutic efficacy of doxorubicin. The prolonged circulation and promoted reaction efficacy of these nanocascades underscore their substantial potential in enzyme replacement therapy and the treatment of various diseases.
      Cover page: A Multi‐Enzyme Nanocascade to Target Disease‐Relevant Metabolites
      • Multimedia
      • Peer Reviewed
      UCLA Previously Published Works (2025)
      Lymphoma, a common malignancy of the lymphatic system, presents considerable health challenges and imposes a significant economic burden. Despite advancements in chemotherapy and immunotherapy that have improved survival rates, issues such as high relapse rates and treatment resistance remain pressing concerns. This study presents a novel therapeutic strategy that combines rituximab with a therapeutic vaccine for human B-cell non-Hodgkin lymphoma, evaluated in a humanized mouse model. This combination therapy synergistically achieves superior tumor suppression and relapse prevention. By harnessing the tumor-killing efficacy of monoclonal antibodies and the T cell-mediated immunity elicited by vaccines, this approach represents a promising advancement in achieving significantly improved cancer treatment outcomes.
      • 1 supplemental ZIP
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2023)
      Cancer immunotherapy has reshaped the landscape of cancer treatment. However, its efficacy is still limited by tumor immunosuppression associated with the excessive production of lactate by cancer cells. Although extensive efforts have been made to reduce lactate concentrations through inhibition of lactate dehydrogenase, such inhibitors disrupt the metabolism of healthy cells, causing severe nonspecific toxicity. We report herein a nanocapsule enzyme therapeutic based on lactate oxidase, which reduces lactate concentrations and releases immunostimulatory hydrogen peroxide, averting tumor immunosuppression and improving the efficacy of immune checkpoint blockade treatment. As demonstrated in a murine melanoma model and a humanized mouse model of triple-negative breast cancer, this enzyme therapeutic affords an effective tool toward more effective cancer immunotherapy.
        Cover page: Lactate oxidase nanocapsules boost T cell immunity and efficacy of cancer immunotherapy
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2021)
        Atmospheric neutrinos are one of the most relevant natural neutrino sources that can be exploited to infer properties about cosmic rays and neutrino oscillations. The Jiangmen Underground Neutrino Observatory (JUNO) experiment, a 20 kton liquid scintillator detector with excellent energy resolution is currently under construction in China. JUNO will be able to detect several atmospheric neutrinos per day given the large volume. A study on the JUNO detection and reconstruction capabilities of atmospheric $\nu_e$ and $\nu_\mu$ fluxes is presented in this paper. In this study, a sample of atmospheric neutrino Monte Carlo events has been generated, starting from theoretical models, and then processed by the detector simulation. The excellent timing resolution of the 3'' PMT light detection system of JUNO detector and the much higher light yield for scintillation over Cherenkov allow to measure the time structure of the scintillation light with very high precision. Since $\nu_e$ and $\nu_\mu$ interactions produce a slightly different light pattern, the different time evolution of light allows to discriminate the flavor of primary neutrinos. A probabilistic unfolding method has been used, in order to infer the primary neutrino energy spectrum from the detector experimental observables. The simulated spectrum has been reconstructed between 100 MeV and 10 GeV, showing a great potential of the detector in the atmospheric low energy region.
          Cover page: JUNO sensitivity to low energy atmospheric neutrino spectraCreative Commons 'BY' version 4.0 license
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2021)
          The OSIRIS detector is a subsystem of the liquid scintillator fillling chain of the JUNO reactor neutrino experiment. Its purpose is to validate the radiopurity of the scintillator to assure that all components of the JUNO scintillator system work to specifications and only neutrino-grade scintillator is filled into the JUNO Central Detector. The aspired sensitivity level of $10^{-16}$ g/g of $^{238}$U and $^{232}$Th requires a large ($\sim$20 m$^3$) detection volume and ultralow background levels. The present paper reports on the design and major components of the OSIRIS detector, the detector simulation as well as the measuring strategies foreseen and the sensitivity levels to U/Th that can be reached in this setup.
            Cover page: The Design and Sensitivity of JUNO's scintillator radiopurity pre-detector OSIRISCreative Commons 'BY' version 4.0 license
            • Article
            • Peer Reviewed

            Feasibility and physics potential of detecting 8B solar neutrinos at JUNO * *This work was supported by the Chinese Academy of Sciences, the National Key R&D Program of China, the CAS Center for Excellence in Particle Physics, the Joint Large-Scale Scientific Facility Funds of the NSFC and CAS, Wuyi University, and the Tsung-Dao Lee Institute of Shanghai Jiao Tong University in China, the Institut National de Physique Nucléaire et de Physique de Particules (IN2P3) in France, the Istituto Nazionale di Fisica Nucleare (INFN) in Italy, the Fond de la Recherche Scientifique (F.R.S-FNRS) and FWO under the “Excellence of Science – EOS” in Belgium, the Conselho Nacional de Desenvolvimento Científico e Tecnològico in Brazil, the Agencia Nacional de Investigación y Desarrollo in Chile, the Charles University Research Centre and the Ministry of Education, Youth, and Sports in Czech Republic, the Deutsche Forschungsgemeinschaft (DFG), the Helmholtz Association, and the Cluster of Excellence PRISMA+ in Germany, the

            UC Irvine Previously Published Works (2021)
            The Jiangmen Underground Neutrino Observatory (JUNO) features a 20 kt multi-purpose underground liquid scintillator sphere as its main detector. Some of JUNO's features make it an excellent location for 8B solar neutrino measurements, such as its low-energy threshold, high energy resolution compared with water Cherenkov detectors, and much larger target mass compared with previous liquid scintillator detectors. In this paper, we present a comprehensive assessment of JUNO's potential for detecting 8B solar neutrinos via the neutrino-electron elastic scattering process. A reduced 2 MeV threshold for the recoil electron energy is found to be achievable, assuming that the intrinsic radioactive background 238U and 232Th in the liquid scintillator can be controlled to 10-17g/g. With ten years of data acquisition, approximately 60,000 signal and 30,000 background events are expected. This large sample will enable an examination of the distortion of the recoil electron spectrum that is dominated by the neutrino flavor transformation in the dense solar matter, which will shed new light on the inconsistency between the measured electron spectra and the predictions of the standard three-flavor neutrino oscillation framework. If Δm221= 4.8 × 10-5(7.5 × 10-5) eV, JUNO can provide evidence of neutrino oscillation in the Earth at approximately the 3σ (2σ) level by measuring the non-zero signal rate variation with respect to the solar zenith angle. Moreover, JUNO can simultaneously measure Δm221using 8B solar neutrinos to a precision of 20% or better, depending on the central value, and to sub-percent precision using reactor antineutrinos. A comparison of these two measurements from the same detector will help understand the current mild inconsistency between the value of Δm221reported by solar neutrino experiments and the KamLAND experiment.
              Cover page: Feasibility and physics potential of detecting 8B solar neutrinos at JUNO * *This work was supported by the Chinese Academy of Sciences, the National Key R&D Program of China, the CAS Center for Excellence in Particle Physics, the Joint Large-Scale Scientific Facility Funds of the NSFC and CAS, Wuyi University, and the Tsung-Dao Lee Institute of Shanghai Jiao Tong University in China, the Institut National de Physique Nucléaire et de Physique de Particules (IN2P3) in France, the Istituto Nazionale di Fisica Nucleare (INFN) in Italy, the Fond de la Recherche Scientifique (F.R.S-FNRS) and FWO under the “Excellence of Science – EOS” in Belgium, the Conselho Nacional de Desenvolvimento Científico e Tecnològico in Brazil, the Agencia Nacional de Investigación y Desarrollo in Chile, the Charles University Research Centre and the Ministry of Education, Youth, and Sports in Czech Republic, the Deutsche Forschungsgemeinschaft (DFG), the Helmholtz Association, and the Cluster of Excellence PRISMA+ in Germany, the Creative Commons 'BY' version 4.0 license
              • Article
              • Peer Reviewed
              UC Irvine Previously Published Works (2021)
              The Jiangmen Underground Neutrino Observatory (JUNO) is a 20 kton LS detector at 700-m underground. An excellent energy resolution and a large fiducial volume offer exciting opportunities for addressing many important topics in neutrino and astro-particle physics. With 6 years of data, the neutrino mass ordering can be determined at 3-4 sigma and three oscillation parameters can be measured to a precision of 0.6% or better by detecting reactor antineutrinos. With 10 years of data, DSNB could be observed at 3-sigma; a lower limit of the proton lifetime of 8.34e33 years (90% C.L.) can be set by searching for p->nu_bar K^+; detection of solar neutrinos would shed new light on the solar metallicity problem and examine the vacuum-matter transition region. A core-collapse supernova at 10 kpc would lead to ~5000 IBD and ~2000 (300) all-flavor neutrino-proton (electron) scattering events. Geo-neutrinos can be detected with a rate of ~400 events/year. We also summarize the final design of the JUNO detector and the key R&D achievements. All 20-inch PMTs have been tested. The average photon detection efficiency is 28.9% for the 15,000 MCP PMTs and 28.1% for the 5,000 dynode PMTs, higher than the JUNO requirement of 27%. Together with the >20 m attenuation length of LS, we expect a yield of 1345 p.e. per MeV and an effective energy resolution of 3.02%/\sqrt{E (MeV)}$ in simulations. The underwater electronics is designed to have a loss rate <0.5% in 6 years. With degassing membranes and a micro-bubble system, the radon concentration in the 35-kton water pool could be lowered to <10 mBq/m^3. Acrylic panels of radiopurity <0.5 ppt U/Th are produced. The 20-kton LS will be purified onsite. Singles in the fiducial volume can be controlled to ~10 Hz. The JUNO experiment also features a double calorimeter system with 25,600 3-inch PMTs, a LS testing facility OSIRIS, and a near detector TAO.
                Cover page: JUNO Physics and DetectorCreative Commons 'BY' version 4.0 license
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2021)
                We present the calibration strategy for the 20 kton liquid scintillator central detector of the Jiangmen Underground Neutrino Observatory (JUNO). By utilizing a comprehensive multiple-source and multiple-positional calibration program, in combination with a novel dual calorimetry technique exploiting two independent photosensors and readout systems, we demonstrate that the JUNO central detector can achieve a better than 1% energy linearity and a 3% effective energy resolution, required by the neutrino mass ordering determination. [Figure not available: see fulltext.]
                  Cover page: Calibration strategy of the JUNO experimentCreative Commons 'BY' version 4.0 license
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2020)
                  The Taishan Antineutrino Observatory (TAO, also known as JUNO-TAO) is a satellite experiment of the Jiangmen Underground Neutrino Observatory (JUNO). A ton-level liquid scintillator detector will be placed at about 30 m from a core of the Taishan Nuclear Power Plant. The reactor antineutrino spectrum will be measured with sub-percent energy resolution, to provide a reference spectrum for future reactor neutrino experiments, and to provide a benchmark measurement to test nuclear databases. A spherical acrylic vessel containing 2.8 ton gadolinium-doped liquid scintillator will be viewed by 10 m^2 Silicon Photomultipliers (SiPMs) of >50% photon detection efficiency with almost full coverage. The photoelectron yield is about 4500 per MeV, an order higher than any existing large-scale liquid scintillator detectors. The detector operates at -50 degree C to lower the dark noise of SiPMs to an acceptable level. The detector will measure about 2000 reactor antineutrinos per day, and is designed to be well shielded from cosmogenic backgrounds and ambient radioactivities to have about 10% background-to-signal ratio. The experiment is expected to start operation in 2022.
                    Cover page: TAO Conceptual Design Report: A Precision Measurement of the Reactor Antineutrino Spectrum with Sub-percent Energy ResolutionCreative Commons 'BY' version 4.0 license
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