Bioconjugated gold nanoparticles as a contrast agent for detection of small tumors

Abstract

Optoacoustic tomography (OAT) is a medical imaging method for detection of cancerous tumors that uses laser pulses to produce transi ultrasonic waves with spatial profiles replicating distribution of absorbed optical energy. Unlike conventional ultrasonography that uses an external source of acoustic waves, OAT uses transient acoustic waves generated as result of thermal expansion of tissue preferentially heated with short laser pulses. Tissues with different optical properties have different optoacoustic profiles and this enables reconstruction of an acoustic image based on distribution of optical absorption. It is anticipated that the difference in optical absorption between very early tumors and normal tissues might be minimal, justifying application of a contrast agent. Gold Nanoparticles (NP) can be designed to strongly absorb desirable color of laser pulses and effectively produce acoustic waves. Therefore, gold NP can be potentially employed as an optoacoustic contrast agent. We studied sensitivity of optoacoustic imaging in phantoms resembling dimensions and properties of the breast with small objects loaded with gold NPs of various concentrations. Targeted selective loading of breast cancer cells in culture with 40-nm diameter NPs was experimentally demonstrated with electron microscopy and fluorescence labeling techniques. To achieve selective targeting, Herceptin, a monoclonal antibody raised against Her2 receptor was conjugated to NPs using streptavidin-biotin conjugation as a linker. Targeting experiments simultaneously demonstrated that Mab/NPs conjugates inhibit cell proliferation of Her/neu positive cells. These data present the first step in development of a new technology for highly selective cancer chemotherapy with capability to diagnose the presence of malignant tumors and monitor the effects of the treatment.