title: Cell-specific transmembrane injection of molecular cargo with gold nanoparticle-generated transient plasmonic nanobubbles.
abstract: Optimal cell therapies require efficient, selective and rapid delivery of molecular cargo into target cells without compromising their viability. Achieving these goals ex vivo in bulk heterogeneous multi-cell systems such as human grafts is impeded by low selectivity and speed of cargo delivery and by significant damage to target and non-target cells. We have developed a cell level approach for selective and guided transmembrane injection of extracellular cargo into specific target cells using transient plasmonic nanobubbles (PNB) as cell-specific nano-injectors. As a technical platform for this method we developed a laser flow cell processing system. The PNB injection method and flow system were tested in heterogeneous cell suspensions of target and non-target cells for delivery of Dextran-FITC dye into squamous cell carcinoma HN31 cells and transfection of human T-cells with a green fluorescent protein-encoding plasmid. In both models the method demonstrated single cell type selectivity, high efficacy of delivery (96% both for HN31 cells T-cells), speed of delivery (nanoseconds) and viability of treated target cells (96% for HN31 cells and 75% for T-cells). The PNB injection method may therefore be beneficial for real time processing of human grafts without removal of physiologically important cells.
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77005, USA.
authors.forename: Ekaterina Y
authors.initials: EY
authors.lastname: Lukianova-Hleb
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Wagner
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Brenner
authors.forename: Dmitri O
authors.initials: DO
authors.lastname: Lapotko
mesh_terms: D017252:CD3 Complex / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D006046:Gold / Q000737:chemistry*; D006801:Humans; D007267:Injections; D053768:Metal Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D009928:Organ Specificity; D013535:Suspensions; D013601:T-Lymphocytes / Q000378:metabolism; D014162:Transfection
chemical_list: D017252:CD3 Complex; D013535:Suspensions; D006046:Gold