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Enhanced optical breakdown in KB cells labeled with folate-targeted silver-dendrimer composite nanodevices.

ABSTRACT: Enhanced optical breakdown of KB tumor cells folate-targeted with silver-dendrimer composite nanodevices (CNDs) is described. CNDs [(Ag(0))(25)-PAMAM_E5.(NH(2))(42)(NGly)(74)(NFA)(2.7)] were fabricated by reactive encapsulation, using a biocompatible template of dendrimer-folic acid (FA) conjugates. Preferential uptake of the folate-targeted CNDs (of various treatment concentrations and surface functionality) by KB cells was visualized with confocal microscopy and transmission electron microscopy. Intracellular laser-induced optical breakdown threshold and dynamics were detected and characterized by high-frequency ultrasonic monitoring of resulting transient bubble events. When irradiated with a near-infrared, femtosecond laser, the CND-targeted KB cells acted as well-confined activators of laser energy, enhancing nonlinear energy absorption, exhibiting a significant reduction in breakdown threshold and thus selectively promoting intracellular laser-induced optical breakdown.This study presents a novel method to selectively destroy cancer cells by combining biochemical targeting with topical laser irradiation. A human epidermoid cancer cell line was targeted with folated silver-dendrimer composite nanodevices and the labeled cancer cells were subsequently destroyed by the microbubbles generated due the enhanced energy uptake of the silver nanoparticles from the laser irradiation, as compared to unlabeled cells.

SUBMITTER: Tse C

PROVIDER: S-EPMC3026873 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Enhanced optical breakdown in KB cells labeled with folate-targeted silver-dendrimer composite nanodevices.

Tse Christine C Zohdy Marwa J MJ Ye Jing Yong JY O'Donnell Matthew M Lesniak Wojciech W Balogh Lajos L

Nanomedicine : nanotechnology, biology, and medicine 20100929 1

Enhanced optical breakdown of KB tumor cells folate-targeted with silver-dendrimer composite nanodevices (CNDs) is described. CNDs [(Ag(0))(25)-PAMAM_E5.(NH(2))(42)(NGly)(74)(NFA)(2.7)] were fabricated by reactive encapsulation, using a biocompatible template of dendrimer-folic acid (FA) conjugates. Preferential uptake of the folate-targeted CNDs (of various treatment concentrations and surface functionality) by KB cells was visualized with confocal microscopy and transmission electron microscop ...[more]

PMID: 20883823

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Project description:PurposeCluster of differentiation 38 (CD38) is a promising therapeutic target in multiple myeloma (MM) patients and has resulted in the development of several CD38 immunotherapies. Current methods to evaluate CD38 expression in the preclinical setting include ex vivo flow cytometry and immunohistochemistry, which can be cumbersome and do not give whole-body information. In vivo imaging technologies such as positron emission tomography rely on decay of radioisotopes, limiting the number of molecular interactions observed at any given time point. Here, we demonstrate the use of near-infrared (NIR) fluorescence imaging for spatiotemporal monitoring of CD38 expression in preclinical MM using the anti-CD38 daratumumab (DARA) conjugated to the NIR fluorophore IRDye800CW (DARA-IRDye800).ProceduresStability studies with human serum and binding assays with human myeloma cells were performed with DARA-IRDye800. Immunocompromised mice with intra- and extramedullary tumors (n = 5/group) were administered with DARA-IRDye800 for in vivo imaging up to 7 days after injection. Ex vivo biodistribution and flow cytometry studies were performed to validate in vivo imaging results. A separate therapy study was performed in mice with intramedullary tumors that were treated and not treated with DARA at a therapeutic dose (n = 7/group). DARA-IRDye800 was administered for subsequent in vivo and ex vivo imaging in both cohorts of mice.ResultsDARA-IRDye800 maintained stability and had high affinity for CD38 (KD = 3.5 ± 0.05 nM). DARA-IRDye800 demonstrated a 5- and 18-fold increase in contrast in tumor-bearing regions of mice with extra- and intramedullary MM. Finally, mice treated with therapeutic doses of DARA and imaged with DARA-IRDye800 showed an 11-fold decrease in fluorescence intensities in vivo compared with untreated controls.ConclusionsOur studies establish DARA-IRDye800 as a promising contrast agent for preclinical evaluation of CD38 expression and for further investigating myeloma engraftment and kinetics in relation to anti-CD38 therapies.

Dataset Information

Enhanced optical breakdown in KB cells labeled with folate-targeted silver-dendrimer composite nanodevices.

Publications

Enhanced optical breakdown in KB cells labeled with folate-targeted silver-dendrimer composite nanodevices.

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