This dissertation, presented in partial fulfillment of the requirements for the degree of Doctor of Philosophy at The Ohio State University, focuses on targeted drug delivery via the folate receptor (FR). The FR is a highly selective tumor marker overexpressed in over 90% of ovarian carcinomas. Two main strategies for targeted drug delivery to FR-positive tumor cells are discussed: coupling to monoclonal antibodies and coupling to folic acid. Folic acid retains its receptor binding properties when derivatized via its γ-carboxyl group, making it an ideal ligand for targeted drug delivery. The dissertation presents novel approaches to using folate receptor-mediated delivery. First, FR-targeted liposomes were evaluated for their ability to deliver a lipophilic boron compound for neutron capture therapy in FR-positive tumor cells. These liposomes showed specific receptor binding and FR-mediated endocytosis in vitro. Second, pH-sensitive liposome formulations based on the incorporation of oleyl alcohol were evaluated for drug delivery. FR-targeting was combined with these pH-sensitive liposomes, and the results showed that FR-targeted, pH-sensitive liposomes entrapping the membrane-impermeable chemotherapeutic agent cytosine-β-D-arabinofuranoside (araC) exhibited approximately 17 times greater FR-dependent cytotoxicity in an FR-positive cell line compared to araC delivered via non-pH-sensitive liposomes. Third, a novel lipophilic conjugate of folate, folate-polyethylene glycol (PEG)-cholesterol, was synthesized and evaluated for FR-mediated delivery of liposomes to tumor cells. Cholesterol was found to be an effective anchor for incorporating targeting ligands into liposomes. All three approaches demonstrated that folic acid, due to its small size, convenience, simple conjugation chemistry, and lack of immunogenicity, is an ideal ligand for targeted delivery of drug carriers to tumors. The dissertation also includes acknowledgments, a vita, and a list of publications, highlighting the author's contributions to the field of targeted drug delivery and the support received from various institutions and individuals.This dissertation, presented in partial fulfillment of the requirements for the degree of Doctor of Philosophy at The Ohio State University, focuses on targeted drug delivery via the folate receptor (FR). The FR is a highly selective tumor marker overexpressed in over 90% of ovarian carcinomas. Two main strategies for targeted drug delivery to FR-positive tumor cells are discussed: coupling to monoclonal antibodies and coupling to folic acid. Folic acid retains its receptor binding properties when derivatized via its γ-carboxyl group, making it an ideal ligand for targeted drug delivery. The dissertation presents novel approaches to using folate receptor-mediated delivery. First, FR-targeted liposomes were evaluated for their ability to deliver a lipophilic boron compound for neutron capture therapy in FR-positive tumor cells. These liposomes showed specific receptor binding and FR-mediated endocytosis in vitro. Second, pH-sensitive liposome formulations based on the incorporation of oleyl alcohol were evaluated for drug delivery. FR-targeting was combined with these pH-sensitive liposomes, and the results showed that FR-targeted, pH-sensitive liposomes entrapping the membrane-impermeable chemotherapeutic agent cytosine-β-D-arabinofuranoside (araC) exhibited approximately 17 times greater FR-dependent cytotoxicity in an FR-positive cell line compared to araC delivered via non-pH-sensitive liposomes. Third, a novel lipophilic conjugate of folate, folate-polyethylene glycol (PEG)-cholesterol, was synthesized and evaluated for FR-mediated delivery of liposomes to tumor cells. Cholesterol was found to be an effective anchor for incorporating targeting ligands into liposomes. All three approaches demonstrated that folic acid, due to its small size, convenience, simple conjugation chemistry, and lack of immunogenicity, is an ideal ligand for targeted delivery of drug carriers to tumors. The dissertation also includes acknowledgments, a vita, and a list of publications, highlighting the author's contributions to the field of targeted drug delivery and the support received from various institutions and individuals.