Date of Award
2022
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Biotechnology Science and Engineering
Committee Chair
Carmen Scholz
Committee Member
Tatyana Sysoeva
Committee Member
Sharifa Love-Rutledge
Committee Member
Krishnan Chittur
Committee Member
Emanuel Waddell
Subject(s)
Nanotechnology, Drug delivery systems, Drug targeting
Abstract
Theranostic nanoparticles are a type of biodegradable and biocompatible multifunctional nanosystems in combination with diagnostic and therapeutic capabilities for more specific and personalized disease management. However, difficulties still exist in engineering biocompatible theranostic nanoparticles with highly specific to intracellular bacteria and tumor. Development of nanoassemblies which can overcome these difficulties to achieve maximum therapeutic efficacy of the drugs will be discussed in this dissertation. Pseudomonas aeruginosa (PA) is an opportunistic pathogen, which causes serious lung infections in immunocompromised patients. Traditional oral intake of large quantities of small-molecule antibiotics to treat bacterial infections leads to off-target toxicity and development of drug-resistant species. Improved delivery systems of antibiotics to the targeted site of bacterial infections would help reduce the need for a high intake of antibiotics. In this dissertation a nanoassembly with mesoporous silica nanoparticles (MSNs) loaded with an antibiotic and coated with a liposome layer which is tagged with PA targeting ligand was developed. The liposomal shell prevents premature drug release before the nanoassembly approaches the targeted bacteria and also provides a surface for ligand binding. Following successful bacteria eradication, another similar nanoassembly to treat lung cancer cells was developed. It is hypothesized that the acidic tumor vicinity and the lipases will degrade the liposome layer to release the ROS inducing drug and trigger cancer cell apoptosis. For ex-vivo bacterial biofilm eradication, the similar nanosystem was coloaded with an antibiotic and a quorum sensing inhibitor. The nanoparticles were wrapped with a rhamnolipid liposome layer to get pass through the biofilm rhamnolipid shield and tagged with an enzyme which can degrade the biofilm outermost physical barrier. All of these nanoassemblies showed enhanced therapeutic efficacy over the use of free drugs. In a joint project, a simple and rapid point of care test to detect low levels of Mycobacterium smegmatis, which is a strain similar to Mycobacterium tuberculosis, was developed using lectin conjugated multi-core silica coated magnetic nanoparticles (SMNPs), which binds to carbohydrate epitopes in mycobacterial cell wall. All these studies led to successful development of theranostic nanosystems to eradicate infectious diseases and lung cancer cells without causing any cytotoxicity to healthy cells.
Recommended Citation
Rathnayake, Kavini M., "Functionalized nanomaterials as tailored theranostics" (2022). Dissertations. 253.
https://louis.uah.edu/uah-dissertations/253