Targeted drug delivery using carbon nanotubes for cancer therapeutics

Abstract

Even though progress has been made in decreasing cancer mortality, cancer is still one of the major causes of death in US. Chemotherapy the most common cancer treatment has severe and lethal side effects. This thesis reports, the use of single walled carbon nanotubes (SWNT) as novel one-dimensional nanomaterials for cancer treatment and detection. Advantage of SWNTs is, they are capable of delivering therapeutic agents and imaging agents, having the ability to overcome various biological barriers and to localize into the target tissue. The major focus of this PhD thesis is the development of carbon nanotube based targeted cancer drug delivery systems than can be utilized in nanomedicine-based therapy protocols to improve patient outcome. This thesis has five chapters beginning with general background and significance of this work in chapter one. For the first time Head and neck squamous cell carcinoma cells were targeted using epidermal growth factor (EGF) guided SWNTs conjugated to quantum dots for visualization or with cisplatin for killing the cancer cells in vitro/in vivo. EGF-complexed SWNTs towards improved site specific therapeutic targeting of in vivo and in vitro cancer models is clearly demonstrated in the second chapter. Chapter 3 describes the first example of imaging the distribution of drug molecules using scanning transmission electron microscopy for atomic scale visualization and quantitation of single cisplatin molecules attached SWNTs designed for targeted drug-delivery. Chapter 4 demonstrates the distribution and clearance of PEG wrapped SWNT cancer drug delivery vehicles in mice. The successful outcome of cancer chemotherapy often depends on the early detection of the cancer lesion. Chapter 5 describes amperometric enzyme-linked immunoassays for Platelet Factor 4 built on vertically aligned arrays SWNTs forests on pyrolytic graphite surface. The optimized SWNT forests setup was extended to detect multiple biomarkers concurrently in a single serum sample. Horseradish peroxidase was used as label on detection antibodies in the sandwich immunoassay. This chapter demonstrated reproducible and accurate electrochemical detection of PF-4 protein cancer biomarker in serum using a common procedure with SWNT-based immunoarrays. These studies suggest the excellent potential for array fabrication leading to real time multiplexed cancer biomarker detection for point-of-care diagnostic assays.