Ultrasound-enhanced release from liposomes with tunable echogenicity Sanku Mallik, North Dakota State University Fargo, DMR We have developed a general strategy to make any liposomes echogenic by encapsulating ammonium bicarbonate in the interior. In reduced pH (6 or less), the generated CO 2 gas renders the liposomes reflective for diagnostic frequency ultrasound. The disturbance created in the lipid bilayer by the escaping gas bubbles leads to the release of encapsulated contents. We have used this strategy to deliver the anticancer drug doxorubicin in cultured pancreatic cancer cells (PANC1). The liposomes were targeted to the cancer cells by incorporating a folate conjugated lipid in the bilayer. The decreased pH of cell cytosol releases the encapsulated drug, resulting in substantial cell death. Ultrasound-enhanced intracellular pH- triggered release Folate receptor mediated targeting to cancer cells PANC1 cells no liposomes With liposomes + ultrasound

A Native American female student (Jessica Tautzaeur. McNair Scholar) completed her research work on this project in June, She is the co-author on a manuscript. Two high school students worked on the project during the summer months of The students were a part of the North Dakota Governor’s School program. One of these students (Rayat Hossain) worked last summer also and decided to come back. He is a coauthor on a manuscript (currently under review in Molecular Pharmaceutics). Both of these students are coauthors on a manuscript under preparation. Mallik is responsible for teaching Physical Chemistry to the undergraduate students. The contents of this course was modified to include discussions on liposomes and echogenic liposomes. Ultrasound-enhanced release from liposomes with tunable echogenicity Sanku Mallik, North Dakota State University Fargo, DMR

Structure of the lipid used (POPC) and the folate conjugated lipid: Ultrasound-enhanced release from liposomes with tunable echogenicity Sanku Mallik, North Dakota State University Fargo, DMR Release from the liposomes in aqueous buffer: POPC