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Abstract
Cancer is the one of the leading cause of deaths in both economically developed and developing nations. Chemotherapy is an established treatment modality for cancer treatment. One of the frequently used targeting mechanism, passive targeting, for cancer therapy makes use of enhanced permeability and retention effect that results in entry and thus accumulation of chemotherapeutic drug in tumor tissue. However, these passive targeting strategies employed in cancer treatment may also result in systemic toxicity, as the delivery vehicles cannot differentiate tumor tissue from healthy tissue, thus resulting in accumulation of drug in healthy tissues. Therefore, there was a need to develop more efficient targeted oncotherapies which has led to the development of active targeting systems. This thesis focuses on the development of active targeting strategies and their application in cancer phototherapy.
First chapter provides an overview of active targeting strategies that have been employed for cancer phototherapy. Chapter 2 focuses on synthesis of sulfonated polymers, targeting abilities of these polymers to selectins followed by assessment of their phototherapeutic properties. Chapter 3 is an extension of the sulfonated polymers further modified to conjugate mannose to enable bimodal targeting abilities for gene delivery and phototherapy. Chapter 4 focuses on the preparation and characterization of folic acid (FA) conjugated porphyrin phospholipid (PoP) liposomes for chemophototherapy. FA-PoP liposomes were loaded with chemotherapeutic drug, Doxorubicin (Dox). Inclusion of PoP in liposome bilayer aided light-triggered Dox release. Folate targeting of FA-PoP liposomes was assessed in vitro in KB cells and in vivo on KB tumor xenografts. Chemophototherapy carried out on mice injected with Dox-loaded folate-targeting liposomes demonstrated tumor growth inhibition with single laser treatment.