title: Formulation and in vitro characterization of composite biodegradable magnetic nanoparticles for magnetically guided cell delivery.
abstract: OBJECTIVE
  Cells modified with magnetically responsive nanoparticles (MNP) can provide the basis for novel targeted therapeutic strategies. However, improvements are required in the MNP design and cell treatment protocols to provide adequate magnetic properties in balance with acceptable cell viability and function. This study focused on select variables controlling the uptake and cell compatibility of biodegradable polymer-based MNP in cultured endothelial cells.
  
  
  METHODS
  Fluorescent-labeled MNP were formed using magnetite and polylactide as structural components. Their magnetically driven sedimentation and uptake were studied fluorimetrically relative to cell viability in comparison to non-magnetic control conditions. The utility of surface-activated MNP forming affinity complexes with replication-deficient adenovirus (Ad) for transduction achieved concomitantly with magnetic cell loading was examined using the green fluorescent protein reporter.
  
  
  RESULTS
  A high-gradient magnetic field was essential for sedimentation and cell binding of albumin-stabilized MNP, the latter being rate-limiting in the MNP loading process. Cell loading up to 160 pg iron oxide per cell was achievable with cell viability >90%. Magnetically driven uptake of MNP-Ad complexes can provide high levels of transgene expression potentially useful for a combined cell/gene therapy.
  
  
  CONCLUSIONS
  Magnetically responsive endothelial cells for targeted delivery applications can be obtained rapidly and efficiently using composite biodegradable MNP.
authors.affiliation: Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA. chorny@email.chop.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Chorny
authors.forename: Ivan S
authors.initials: IS
authors.lastname: Alferiev
authors.forename: Ilia
authors.initials: I
authors.lastname: Fishbein
authors.forename: Jillian E
authors.initials: JE
authors.lastname: Tengood
authors.forename: Zoë
authors.initials: Z
authors.lastname: Folchman-Wagner
authors.forename: Scott P
authors.initials: SP
authors.lastname: Forbes
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Levy
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D002417:Cattle; D002470:Cell Survival; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D004355:Drug Stability; D042783:Endothelial Cells / Q000378:metabolism*; D052203:Ferrosoferric Oxide / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D018014:Gene Transfer Techniques; D007700:Kinetics; D008280:Magnetics; D015394:Molecular Structure; D053758:Nanoparticles; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D005456:Fluorescent Dyes; D011091:Polyesters; D013501:Surface-Active Agents; C033616:poly(lactide); D052203:Ferrosoferric Oxide