Gold hybrid nanoparticles for targeted phototherapy and cancer imaging.
Gold and iron oxide hybrid nanoparticles (HNPs) synthesized by the thermal decomposition technique are bio-functionalized with a single chain antibody, scFv, that binds to the A33 antigen present on colorectal cancer cells. The HNP-scFv conjugates are stable in aqueous solution with a magnetization value of 44 emu g(-1) and exhibit strong optical absorbance at 800 nm. Here we test this material in targeting, imaging and selective thermal killing of colorectal cancer cells. Cellular uptake studies showed that A33-expressing cells take up the A33scFv-conjugated HNPs at a rate five times higher than cells that do not express the A33 antigen. Laser irradiation studies showed that approximately 53% of the A33-expressing cells exposed to targeted HNPs are killed after a six-minute laser treatment at 5.1 W cm(-2) using a 808 nm continuous wave laser diode while < 5% of A33-nonexpressing cells are killed. At a higher intensity, 31.5 W cm(-2), the thermal destruction increases to 99 and 40% for A33-expressing cells and A33 nonexpressing cells, respectively, after 6 min exposure. Flow cytometric analyses of the laser-irradiated A33 antigen-expressing cells show apoptosis-related cell death to be the primary mode of cell death at 5.1 W cm(-2), with increasing necrosis-related cell death at higher laser power. These results suggest that this new class of bio-conjugated hybrid nanoparticles can potentially serve as an effective antigen-targeted photothermal therapeutic agent for cancer treatment as well as a probe for magnetic resonance-based imaging.
Graduate Field of Biomedical Engineering, Cornell University, Ithaca, NY, USA. dk322@cornell.edu
Dickson K
DK
Kirui
Diego A
DA
Rey
Carl A
CA
Batt
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005290:Ferric Compounds / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D019073:HT29 Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry*; D009369:Neoplasms / Q000473:pathology* / Q000628:therapy; D010789:Phototherapy / Q000379:methods*; D057127:Single-Chain Antibodies / Q000737:chemistry*
D005290:Ferric Compounds; C104258:GPA33 protein, human; D008562:Membrane Glycoproteins; D057127:Single-Chain Antibodies; C000499:ferric oxide; D006046:Gold