Aminoglycosides contain a basic unit of an amino-modified glycoside (sugar) and have potent antibacterial properties used to treat a wide range of bacterial infections, including those that occur in the soft tissue, chest, urinary tract, and endocardial tissue.1, 2 With a broad spectrum of activity and convenient dosing schedule, Aminoglycoside helps to effectively fight off Gram-negative bacteria.1, 3 In 1944 an aminoglycoside called streptomycin entered clinical trials to test its effectiveness as an antibiotic.4 After several years other classes of aminoglycosides were discovered such as neomycin, gentamicin, kanamycin, and netilmicin.4 When introduced these antibiotics presented major clinical advancements in the treatment of Tuberculosis and other bacterial infections.3, 4 However their use in modern medicine has diminished due to their toxicity, required parenteral delivery, and the availability of alternative antibiotics.3, 5 The dose-dependent toxicity of aminoglycosides limits their use due to a narrow range of safe aminoglycoside plasma concentrations.3, 5 Exceeding this range in non-target tissues can lead to negative effects on the audio-vestibular apparatus and kidneys.3, 5, 6 In the 1980’s, clinicians began treating infections with antibiotics that were perceived as less toxic and providing broader antibacterial activity.7 This resulted in aminoglycosides being prescribed for more persistent infections that were resistant to other antibiotics.3 With the amount of antibiotic resistant bacteria increasing, many scientists have begun looking into methods for minimizing aminoglycoside toxicity and maximizing its antibacterial activity.3, 8 These methods include encapsulation and polymer conjugation.9, 10 By encapsulating aminoglycosides in liposomes or other vesicles scientists aim to increase its concentration in infected tissues while decreasing nephro- and ototoxicity.9 With conjugated polymers scientists have created polymer complexes containing aminoglycosides and other compounds such as dopamine.11 The goal of these polymers is to limit toxicity by slowing antibiotic release and increasing efficacy of the antibiotic through targeted delivery and toxicity of other compounds.9, 10, 11 Other than its use in treating infections, aminoglycosides are gaining attention as an excellent vehicle for gene delivery.12 In this application aminoglycosides are used to correct a genetic defect by introducing a normal copy of the gene into affected cells.12,13 Currently scientists are assessing aminoglycosides for gene therapy in the treatment of cancer and various other diseases.12, 14 This review will focus on the diverse customizability of aminoglycosides in treating infections and as vehicles for gene therapy.
Amikagel’s properties were chemo-mechanically tunable and directly impacted the outcome of tumor dormancy or relapse. Exposure of dormant spheroids to weakly stiff and adhesive formulation of Amikagel resulted in significant relapse, mimicking the response to changes in extracellular matrix around dormant tumors. Relapsed cells showed significant differences in their metastatic potential compared to the cells that remained dormant after the induction of relapse. Further, the dissertation discusses the use of Amikagels as novel pDNA binding resins in microbead and monolithic formats for potential use in chromatographic purifications. High abundance of amino groups allowed their utilization as novel anion-exchange pDNA binding resins. This dissertation discusses Amikagel formulations for pDNA binding, metastatic cancer cell separation and novel drug discovery against tumor dormancy and relapse.
In this work, plasmonic nanocomposites have been synthesized and used in laser tissue welding for ruptured porcine intestine ex vivo and incised murine skin in vivo. These laser-responsive nanocomposites improved tissue strength and healing, respectively. Additionally, a spatiotemporal model has been developed for laser tissue welding of porcine and mouse cadaver intestine sections using near-infrared laser irradiation. This mathematical model can be employed to identify optimal conditions for minimizing healthy cell death while still achieving a strong seal of the ruptured tissue using laser welding. Finally, in a model of surgical site infection, laser-responsive nanomaterials were shown to be efficacious in inhibiting bacterial growth. By incorporating an anti-microbial functionality to laser-responsive nanocomposites, these materials will serve as a treatment modality in sealing tissue, healing tissue, and protecting tissue in surgery.