工艺Chiral porphyrazine near-IR optical imaging agent.pdfVIP

Chiral porphyrazine near-IR optical imaging agent exhibiting preferential tumor accumulation a a,b c c c c Evan R. Trivedi , Allison S. Harney , Mary B. Olive , Izabela Podgorski , Kamiar Moin , Bonnie F. Sloane , Anthony G.M. Barrettd, Thomas J. Meadea,b, and Brian M. Hoffmana,1 a Departments of Chemistry and Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL, 60208; bDepartments of Neurobiology, Physiology, and Radiology, Northwestern University, Evanston, IL, 60208; c Department of Pharmacology and Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, 48201; and d Department of Chemistry, Imperial College of Science, Technology and Medicine, South Kensington, London SW7 2AZ, United Kingdom Contributed by Brian M. Hoffman, Northwestern University, Evanston, IL, November 9, 2009 (sent for review October 7, 2009) A chiral porphyrazine (pz), H ½pzðtrans-A B Þ (247), has been 2 2 2 prepared that exhibits preferential in vivo accumulation in the cells of tumors. Pz 247 exhibits near-infrared (NIR) emission with λ 700 nm in the required wavelength range for maximum tissue penetration. When MDA-MB-231 breast tumor cells are treated with 247, the agent shows strong intracellular fluorescence with an emission maximum, 704 nm, which indicates that it localizes within a hydrophobic microenvironment. Pz 247 is shown to asso- ciate with the lipophilic core of LDL and undergo cellular entry primarily through receptor-mediated endocytosis accumulating in lysosomes. Preliminary in vivo studies show that 247 exhibits preferential accumulation and retention in the cells of MDA-MB- 231 tumors subcutane