| Popis: |
Since the discovery of cisplatin, the development of platinum-based chemotherapeutic drugs hastransformed the treatment of multiple cancers. Lately, these account for almost half of all agentsused in clinical chemotherapy 1. Despite their widespread use and initial effectiveness for specificcancers, several drawbacks exist which limit both the cure rate and the patient’s survival. Thedrug’s premature reduction in the blood stream, low tumor selectivity2, and drug resistance aresome of the major downsides in the long-term usage of cisplatin; thus, finding ways to alleviatethese drawbacks remains pivotal in the effective treatment of cancers. Herein, our work focuseson the development of platinum-based anticancer drugs that have less premature drug reduction,greater tumor selectivity, and overcome drug resistance by targeting the mitochondria of cancercells.The first chapter of my dissertation describes the introduction and background of platinum basedanticancer drugs. Synthesis, cell-based studies, and analysis of the following topics will bediscussed in later chapters.I. Engineering liposomal nanoparticles of cholesterol-tethered amphiphilic Pt (IV)prodrugs with prolonged circulation time in bloodIn chapter two of my dissertation, we present a stabilized liposomal formulation of the platinum.anticancer drug. A cholesterol conjugated amphiphilic Pt (IV) prodrug of cisplatin is synthesizedand encapsulated in liposomal formulation. This formulation shows marked resistance againstpremature reduction in human plasma and increased the half-life of Pt(IV) prodrug to over sixtimes that of cisplatin. The paper has been published in 2020.II. Development of mitochondria targeting Pt (IV)- Ru (II) binuclear complex to treatovarian cancerIn chapter three of my dissertation, we present a novel design of Ru (bpy)2 conjugated fatty acidlike Pt(IV) prodrug. This binuclear organometallic complex shows enhanced efficacy to treatovarian cancer by targeting and damaging mitochondria, the powerhouse of cell. Manuscript iscurrently under preparation.III. Optimization of potency of Pt (IV) prodrugs via a small library of Pt (IV)derivativesChapter four of my dissertation will be focused on the development and evaluation of a smalllibrary of fatty acid like Pt(IV) prodrug derivatives’ efficacy. These prodrugs are designed to targetmitochondria to eliminate resistant cancer cells. The modification of head groups using variousfunctional group and varying the carbon chain length, a comparative analysis will be discussedbased on cancerous cell damaging effectiveness. Manuscript is currently under preparation. |
