A pretargeted nanoparticle system for tumor cell labeling.
Nanoparticle-based cancer diagnostics and therapeutics can be significantly enhanced by selective tissue localization, but the strategy can be complicated by the requirement of a targeting ligand conjugated on nanoparticles, that is specific to only one or a limited few types of neoplastic cells, necessitating the development of multiple nanoparticle systems for different diseases. Here, we present a new nanoparticle system that capitalizes on a targeting pretreatment strategy, where a circulating fusion protein (FP) selectively prelabels the targeted cellular epitope, and a biotinylated iron oxide nanoparticle serves as a secondary label that binds to the FP on the target cell. This approach enables a single nanoparticle formulation to be used with any one of existing fusion proteins to bind a variety of target cells. We demonstrated this approach with two fusion proteins against two model cancer cell lines: lymphoma (Ramos) and leukemia (Jurkat), which showed 72.2% and 91.1% positive labeling, respectively. Notably, TEM analysis showed that a large nanoparticle population was endocytosed via attachment to the non-internalizing CD20 epitope.
Department of Materials Science and Engineering, University of Washington, Seattle, WA 98195, USA.
Jonathan
J
Gunn
Steven I
SI
Park
Omid
O
Veiseh
Oliver W
OW
Press
Miqin
M
Zhang
D001710:Biotin / Q000737:chemistry; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D007938:Leukemia / Q000175:diagnosis*; D008024:Ligands; D008223:Lymphoma / Q000175:diagnosis*; D053758:Nanoparticles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000627:therapeutic use*; D013194:Staining and Labeling
D005290:Ferric Compounds; D008024:Ligands; D011993:Recombinant Fusion Proteins; C000499:ferric oxide; D011092:Polyethylene Glycols; D001710:Biotin; D048271:Chitosan