title: Nanoparticulate cellular patches for cell-mediated tumoritropic delivery.
abstract: The targeted delivery of therapeutics to tumors remains an important challenge in cancer nanomedicine. Attaching nanoparticles to cells that have tumoritropic migratory properties is a promising modality to address this challenge. Here we describe a technique to create nanoparticulate cellular patches that remain attached to the membrane of cells for up to 2 days. NeutrAvidin-coated nanoparticles were anchored on cells possessing biotinylated plasma membrane. Human bone marrow derived mesenchymal stem cells with nanoparticulate patches retained their inherent tumoritropic properties as shown using a tumor model in a 3D extracellular matrix. Additionally, human umbilical vein endothelial cells with nanoparticulate patches were able to retain their functional properties and form multicellular structures as rapidly as unmodified endothelial cells. These results provide a novel strategy to actively deliver nanostructures and therapeutics to tumors utilizing stem cells as carriers and also suggest that nanoparticulate cellular patches may have applications in tissue regeneration.
authors.affiliation: The David H. Koch Institute for Integrative Cancer Research, Massachusetts Instituteof Technology, Cambridge, MA 02139, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Cheng
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Kastrup
authors.forename: Renuka
authors.initials: R
authors.lastname: Ramanathan
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Siegwart
authors.forename: Minglin
authors.initials: M
authors.lastname: Ma
authors.forename: Said R
authors.initials: SR
authors.lastname: Bogatyrev
authors.forename: Qiaobing
authors.initials: Q
authors.lastname: Xu
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Whitehead
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use; D019921:Biotinylation; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers