Zachary Lyles

Dissertation Defense

Synthesis, Characterization, and Application of Silica-Based Nanoparticulate Platforms for the Delivery of Photosensitizers in the Use of Photodynamic Therapy for Cancer Treatment

 

Abstract:

Triple negative breast cancer (TNBC) is a subtype of Breast cancer which lacks expressions of hormone receptors (ER/PR/HER2) and other meaningful targets. TNBC is characterized by intra-tumor heterogeneities, high proliferative activity, poor prognosis, aggressive relapse, and metastasis to lungs and brain, making the disease clinically challenging to treat. Approximately 50% of the patients diagnosed with early-stage TNBC experience recurrence, and 37% die within the first 5 years after surgery. Due to the aggressive nature of TNBC, novel therapeutic alternatives are of interest to improve clinical outcome of this deadly disease.

PDT is a promising non-toxic, minimally invasive light-based therapy which causes cell death and triggers anti-tumor immune response. PDT combats many negative side effects associated with more commonly used treatments such as chemotherapy and radiation therapy. PDT provides benefits, as it is minimally invasive, produces minor damage to healthy tissue, and does not require long therapeutic follow-ups, making it a patient-friendly therapeutic modality.

This Ph.D. thesis is aimed to develop and evaluate the phototherapeutic effects of three strategies for the treatment of highly aggressive TNBC: 1) a novel redox-responsive polysilsesquioxane-based nanoparticle system for the delivery of PpIX (PpIX-PSilQ NPs), 2) Mesoporous silica nanoparticle-based PDT platform for the combinatorial delivery of PS chlorin e6 and chemotherapy agent cisplatin, Ce6 cisPt MSN, and 3) PpIX-PSilQ NPs based platform for the delivery of PpIX, a multitargeting agent(curcumin) and siRNA. Each of the nanoplatforms were synthesized, characterized and their phototherapeutic properties were evaluated in TNBC cell lines and in vivo orthotopic TNBC models.

Sponsoring Chair: Dr. Juan Vivero-Escoto 
Committee: Dr. Thomas A. Schmedake, Dr. Nathaniel Fried, Dr. Michael G. Walter

Defense Date: Thursday, November 1, 2018 at 11:30 AM