| Despite remarkable advances in drug development and diagnostic technologies, cancer continues to be a major contributor to global morbidity and mortality. Greater understanding of the signaling pathways and biological processes has led to discovery of novel therapeutic targets, prolonged survival times, and overall enhanced management of the disease. Nonetheless, victory in the battle against cancer remains a huge struggle for humanity.;Currently, surgical resection and radiation therapy remain the front-line strategies in treating localized early stage solid tumors, while conventional systemic chemotherapy continues to be the mainstream approach in management of almost all types and stages of cancer. Several major limitations significantly impede the successful pharmacotherapeutic treatment of cancer. This dissertation focuses on two of the most common and restraining barriers, including severe systemic toxicities and multi-drug resistance (MDR). The highly potent chemotherapy agents lack selectivity and additionally induce their cytotoxic effects on highly perfused organs and rapidly dividing healthy cells. MDR, on the other hand is the intrinsic or acquired cross-resistance of cancer cells to diverse classes of molecules, yielding failed responses to chemotherapy and increased aggressiveness of the disease. Consequently, it is vital to develop more efficient strategies and design specific treatment regimens. Furthermore, the emerging concept of theranostics has shed light on improving and individualizing cancer management via combining diagnosis and therapy guided by a non-invasive imaging technique.;A multi-disciplinary approach was employed to engineer a novel drug delivery system as well as investigate a bi-modal treatment strategy to enhance the effectiveness of anti-cancer agents. Accordingly, indocyanine green (ICG), a near-infrared fluorescent dye, was thoroughly investigated in free and liposomal forms for fluorescent optical behavior as well as thermal and photo stability. Subsequently, bi-functional thermosensitive liposomes co-encapsulated with doxorubicin and ICG were engineered for triggered release and potential image-guided delivery. The delivery system displayed stability at 37 °C, while managing to liberate the encapsulated doxorubicin upon induction of mild hyperthermia (42 °C). Cytotoxicity results also correlated with the release kinetics profile. Furthermore, investigation of cellular uptake revealed the thermosensitive liposomes following mild hyperthermia to possess similar drug uptake as that of free doxorubicin.;ICG was also used as a photosensitizer in bi-modal treatment of resistant ovarian carcinoma cells to circumvent MDR. The two strategies consisted of photodynamic therapy (PDT) and chemotherapy. Synergistic or additive cytotoxic effects were achieved in the sensitive strain, whereas the resistant cells exhibited resistance to both modalities, alone and in combination. |
