Phage display is a molecular technique accomplished by incorporation of the nucleotide sequence encoding the protein to be displayed into a phage or phagemid genome as a fusion to a gene encoding a phage coat protein. After several rounds of selection and amplification, high affinity phage clones, and thus high affinity ¡§homing peptides¡¨ can be obtained. Cell-binding homing peptides selected in this manner could be linked by physical or genetic manipulation to gene therapy vectors that mediate their own entry (viral or non-viral vectors) to facilitate targeting. Homing peptides that target specific cellular receptors can also be used as a treatment modality to induce various signal transduction pathways or even apoptotic signals of cancer cells. Oral squamous cell carcinoma (OSCC) is one of the most common cancers in the world. It has become the fourth cancer death reason of males in Taiwan. Radical surgery combined with postoperative chemotherapy and/or radiotherapy is still the major modality for treatment of OSCC. The 5-year survival rate of OSCC is still discouraged in recent years. Patients with OSCC present numerous challenges to treating physicians. In this study, we aimed to isolate and identify homing phage clones specific to oral cancer cells by panning with a random phage peptide library. The homing phage clones will be used as a basis to improve targeting specificity of gene therapy vectors. A NCBI BLAST search was performed and close similarities were found to several important molecules biologically with the homing peptides carried by phage clones. Characterization of the selected phage-29 was then studied by immunohistochemical methods. Internalization of this phage-29 is sequence-specific and mediated by integrin £\v£]6 in HSC-3 cells rapidly. We also confirmed that the integrin £\v£]6-targeting homing peptide is universally useful in all major kinds of head and neck cancer. We will further study the possible biological functions of the other homing peptides to see whether these peptides could have potential applications for oral cancer treatment.

Pregnancy complications such as fetal growth restriction (FGR) are often attributed to poor uteroplacental blood flow, but the risk of systemic side-effects hinders therapeutic intervention. We have utilised novel placental-specific homing peptides to overcome this and have conjugated these to biocompatible liposomes. Peptide-conjugated liposomes were found to selectively bind to the outer syncytiotrophoblast layer of the human placenta and to the uteroplacental vasculature and labyrinth region of the mouse placenta. The novel vasodilator SE175 was selected as a nitric oxide donor with a favourable stability and release profile, to encapsulate in peptide-conjugated liposomes in an attempt to restore impaired uteroplacental blood flow in a mouse model of FGR, the endothelial nitric oxide synthase knockout mouse. Liposomes containing SE175 or PBS were prepared by lipid film hydration and targeting peptides coupled to the liposomal surface. Vehicle control, free SE175, PBS- or SE175-containing liposomes were intravenously injected on embryonic (E) days 11.5, 13.5, 15.5 and 17.5. Animals were sacrificed at E18.5 and fetal and placental weights recorded. Targeted delivery of SE175 significantly increased fetal weight compared to vehicle control but no other treatment groups, whilst significantly decreasing placental weight, indicating improved placental efficiency. Treatment was well tolerated, having no impact on litter size or resorptions. Targeted delivery of SE175, but no other treatment group, reduced a marker of lipid peroxidation in the placenta, indicating a reduction in oxidative stress. These data suggest that selective delivery of SE175 to the uteroplacental vasculature in peptide decorated liposomes may represent a novel treatment for FGR.