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Folate Receptor-Targeting Liposomes For The Delivery Of Antisense Molecules To Cancer Cells, Colin J. Way Aug 2013

Folate Receptor-Targeting Liposomes For The Delivery Of Antisense Molecules To Cancer Cells, Colin J. Way

Electronic Thesis and Dissertation Repository

RNAi (RNA interference) is emerging as a promising tool for cancer therapy. Small interfering RNA (siRNA) molecules are activated in that pathway to reduce specific tumour cell RNAs that mediate malignancy. SiRNA treatment has been primarily limited to in vitro studies: lack of efficient, preferential in vivo delivery to target cells remains a major obstacle. Many human tumours overexpress folate receptors (FR), and siRNA-mediated reduction of thymidylate synthase (TS) sensitizes tumour cells to anti-TS drugs. I developed a folate-containing cationic liposome to preferentially deliver anti-TS siRNA to FR-expressing human tumour cells. I show, in vitro, that liposome-encapsulated siRNA (but …


Turning Stealth Liposomes Into Cationic Liposomes For Anticancer Drug Delivery, Vijay Gyanani Jan 2013

Turning Stealth Liposomes Into Cationic Liposomes For Anticancer Drug Delivery, Vijay Gyanani

University of the Pacific Theses and Dissertations

Targeting the anticancer agents selectively to cancer cells is desirable to improve the efficacy and to reduce the side effects of anticancer therapy. Previously reported passive tumor targeting by PEGylated liposomes (stealth liposomes) have resulted in their higher tumor accumulation. However their interaction with cancer cells has been minimal due to the steric hindrance of the PEG coating. This dissertation reports two approaches to enhance the interaction of stealth liposomes with cancer cells. First, we designed a lipid-hydrazone-PEG conjugate that removes the PEG coating at acidic pH as in the tumor interstitium. However, such a conjugate was highly unstable on …