SYNTHESIS, CHARACTERIZATION, AND APPLICATION OF SILICA-BASED NANOPARTICULATE PLATFORMS FOR THE DELIVERY OF PHOTOSENSITIZERS IN THE USE OF PHOTODYNAMIC THERAPY FOR CANCER TREATMENT

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Lyles, Z. (2018). SYNTHESIS, CHARACTERIZATION, AND APPLICATION OF SILICA-BASED NANOPARTICULATE PLATFORMS FOR THE DELIVERY OF PHOTOSENSITIZERS IN THE USE OF PHOTODYNAMIC THERAPY FOR CANCER TREATMENT. Unc Charlotte Electronic Theses And Dissertations.
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Abstract

Triple negative breast cancer (TNBC) is a subtype of breast cancer which lacks expressions of hormonal receptors (ER/PR/HER2) and other meaningful targets. TNBC is characterized by intra-tumoral heterogeneities, high proliferative activity, poor prognosis, aggressive relapse, and distant 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. Photodynamic therapy (PDT) is a promising non-toxic, minimally invasive light-based therapy which causes cell death and triggers anti-tumor immune response. Photodynamic therapy (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 independent strategies for the treatment of highly aggressive TNBC; 1) a novel redox-responsive polysilsesquioxane-based nanoparticle system for the delivery of photosensitizer (PS) protoporphyrin IX (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, 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.

Details
Author

Lyles, Zachary

Title

SYNTHESIS, CHARACTERIZATION, AND APPLICATION OF SILICA-BASED NANOPARTICULATE PLATFORMS FOR THE DELIVERY OF PHOTOSENSITIZERS IN THE USE OF PHOTODYNAMIC THERAPY FOR CANCER TREATMENT

Physical Description

1 online resource (157 pages) : PDF

Date

2018

Degree Granting Institution

University of North Carolina at Charlotte

Abstract

Triple negative breast cancer (TNBC) is a subtype of breast cancer which lacks expressions of hormonal receptors (ER/PR/HER2) and other meaningful targets. TNBC is characterized by intra-tumoral heterogeneities, high proliferative activity, poor prognosis, aggressive relapse, and distant 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. Photodynamic therapy (PDT) is a promising non-toxic, minimally invasive light-based therapy which causes cell death and triggers anti-tumor immune response. Photodynamic therapy (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 independent strategies for the treatment of highly aggressive TNBC; 1) a novel redox-responsive polysilsesquioxane-based nanoparticle system for the delivery of photosensitizer (PS) protoporphyrin IX (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, 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.

Genre

doctoral dissertations

Subjects--Topics

Nanoscience

Degree

Ph.D.

Subject Area

Chemistry

Advisor(s)

Vivero-Escoto, Juan

Committee Members

Ogle, Craig
Walter, Michael
Fried, Nathaniel
Schmedake, Tom

Degree Note

Thesis (Ph.D.)--University of North Carolina at Charlotte, 2018.

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Rights Holder Information

Copyright is held by the author unless otherwise indicated.

Identifier

Lyles_uncc_0694D_11908

Permalink

http://hdl.handle.net/20.500.13093/etd:1214