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Open Access Publications from the University of California

Scholarly Works (3 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2020)

This thesis involves synthesis, derivatization and biomedical applications of mesoporous silica nanoparticles (MSNs) based delivery systems. Chapter 1 introduces the background of MSNs including the advantages of MSNs, modification on MSNs for multifunctionality; formation mechanism, a typical synthesis condition for MCM-41 and following characterizaitons. In chapter 2 & 3, the synthesis and application of target moiety functionalized MSNs for gene therapy in vitro and in vivo are introduced. Chapters 4, & 5 introduce the relevant studies of utilizing MSN based delivery system for the treatment of infectious disease, from a pharmacokinetic study of moxifloxacin delivered by MSNs via different routes, to the enhanced efficacy of MSN based treatment by materials optimizations via inhalation administration route. Chapter 6 discusses the study of a general synthesis method for pore enlargement in various types of MSNs. In Chapter 7, the design and preparation of a thin film consist of ultra large pore-sized mesoporous silica spheres and polymer template macropores is illustrated. Overall, these chapters demonstrate the successful engineering of mesoporous silica nanoparticles and materials optimization and their enhanced performance in biological applications from in vivo tumor shrinkage by gene delivery to antibiotics delivery for enhanced bacterial killing efficacy in mouse model.

    Cover page: Multifunctional mesoporous silica nanoparticles for drug and large molecule delivery
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2017)
    Epithelial ovarian cancer (EOC) is the most deadly gynecologic malignancy on account of its late stage at diagnosis and frequency of drug resistant recurrences. Novel therapies to overcome these barriers are urgently needed. TWIST is a developmental transcription factor reactivated in cancers and linked to angiogenesis, metastasis, cancer stem cell phenotype, and drug resistance, making it a promising therapeutic target. In this work, we demonstrate the efficacy of TWIST siRNA (siTWIST) and two nanoparticle delivery platforms to reverse chemoresistance in EOC models. Polyamidoamine dendrimers and mesoporous silica nanoparticles (MSNs) carried siTWIST into target cells and led to sustained TWIST knockdown in vitro. Mice treated with cisplatin plus MSN-siTWIST exhibited lower tumor burden than mice treated with cisplatin alone, with most of the effect coming from reduction in disseminated tumors. This platform has potential application for overcoming the clinical challenges of metastasis and chemoresistance in EOC and other TWIST overexpressing cancers.
      Cover page: Nanoparticle delivery of siRNA against TWIST to reduce drug resistance and tumor growth in ovarian cancer models
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2019)
      Francisella tularensis causes a serious and often fatal infection, tularemia. We compared the efficacy of moxifloxacin formulated as free drug vs disulfide snap-top mesoporous silica nanoparticles (MSNs) in a mouse model of pneumonic tularemia. We found that MSN-formulated moxifloxacin was more effective than free drug and that the intramuscular and subcutaneous routes were markedly more effective than the intravenous route. Measurement of tissue silica levels and fluorescent flow cytometry assessment of colocalization of MSNs with infected cells revealed that the enhanced efficacy of MSNs and the intramuscular route of delivery was not due to better delivery of MSNs to infected tissues or cells. However, moxifloxacin blood levels demonstrated that the nanoparticle formulation and intramuscular route provided the longest half-life and longest time above the minimal inhibitory concentration. Thus, improved pharmacokinetics are responsible for the greater efficacy of nanoparticle formulation and intramuscular delivery compared with free drug and intravenous delivery.
        Cover page: Nanoparticle Formulation of Moxifloxacin and Intramuscular Route of Delivery Improve Antibiotic Pharmacokinetics and Treatment of Pneumonic Tularemia in a Mouse ModelCreative Commons 'BY' version 4.0 license
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