title: Porous silicon nanocarriers for dual targeting tumor associated endothelial cells and macrophages in stroma of orthotopic human pancreatic cancers.
abstract: Pancreatic cancer is a highly fatal disease characterized by a dominant stroma formation. Exploring new biological targets, specifically those overexpressed in stroma cells, holds significant potential for the design of specific nanocarriers to attain homing of therapeutic and imaging agents to the tumor. In clinical specimens of pancreatic cancer, we found increased expression of CD59 in tumor associated endothelial cells as well as infiltrating cells in the stroma as compared to uninvolved pancreas. We explored this dual targeting effect using orthotopic human pancreatic cancer in nude mice. By immunofluorescence analysis, we confirmed the increased expression of Ly6C, mouse homolog of CD59, in tumor associated endothelial cells as well as in macrophages within the stroma. We decorated the surface of porous silicon nanocarriers with Ly6C antibody. Targeted nanocarriers injected intravenously accumulated to tumor associated endothelial cells within 15min. At 4h after administration, 9.8±2.3% of injected dose/g tumor of the Ly6C targeting nanocarriers accumulated in the pancreatic tumors as opposed to 0.5±1.8% with non-targeted nanocarriers. These results suggest that Ly6C (or CD59) can serve as a novel dual target to deliver therapeutic agents to the stroma of pancreatic tumors.
authors.affiliation: Department of Nanomedicine, The Methodist Hospital Research Institute, 6670 Bertner St., Houston, TX 77030, USA. KYokoi2@tmhs.org
authors.forename: Kenji
authors.initials: K
authors.lastname: Yokoi
authors.forename: Biana
authors.initials: B
authors.lastname: Godin
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Oborn
authors.forename: Jenolyn F
authors.initials: JF
authors.lastname: Alexander
authors.forename: Xuewu
authors.initials: X
authors.lastname: Liu
authors.forename: Isaiah J
authors.initials: IJ
authors.lastname: Fidler
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects; D018957:CD59 Antigens / Q000096:biosynthesis / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D049329:Nanostructures / Q000008:administration & dosage*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D012825:Silicon / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000950:Antigens, Ly; D000970:Antineoplastic Agents; D018957:CD59 Antigens; C494192:Ly-6C antigen, mouse; D012825:Silicon