Molecular imaging of cancer cells with ultra-small 5nm gold nanoparticles.
Sangheon Han1,2, Tomasz Zal3 and Konstantin Sokolov1,2
3Department of Immunology, The UT M.D. Anderson Cancer Center, Houston, TX 77030
This talk will present biologically-induced plasmonic effects in nanoscale spherical gold nanoparticles that can be exploited for multi-modal imaging including dark-field microscopy, reflectance, photoacoustic and two-photon luminescence imaging. Previously, we have demonstrated a strong spectral shift of >100nm and color change of 20 and 40nm gold nanoparticles targeted to epidermal growth factor receptor (EGFR) after their receptor medicated uptake by cancer cells. We showed that this effect is associated with plasmon resonance coupling of gold nanoparticles in cellular endosomal compartments and it allows achieving an unprecedented sensitivity in detection of metastatic foci of ca. 30 cells at depth in vivo in animal models of head and neck cancer.
Currently, we are exploring multimodal nature of ultra-small 5 nm gold nanoparticles in detection of cancer cells. This size domain is comparable (or even smaller) to large biomolecules such as antibodies and it can offer a number of advantages including better intratumoral distribution of nanoparticles, improved delivery and pharmacokinetics. Furthermore, nanoparticles with sizes below than 10nm can undergo efficient body clearance that can facilitate future clinical translation. Our results show that labeling of cancer cells with EGFR-targeted 5nm gold nanoparticles results in a very strong contrast in dark-field and photoacoustic imaging with near-infrared (NIR) excitation that is very similar to the much bigger 20-40 nm particles. Confocal and multi-photon microscopy studies of nanoparticles trafficking in live cells indicate that this strong signal is associated with nanoparticles’ coating degradation inside cells. Interestingly, molecular specific intracellular uptake of 5nm gold nanoparticles results in a very strong two-photon luminescence, which is characterized by broad emission and relatively narrow excitation spectral properties and very short lifetimes. The dual photoacoustic (due to absorption) and luminescence signal from nanoparticles’ labeled cells can be highly advantageous in combining a lower resolution in depth tissue imaging using photoacoustic with a high-resolution two-photon microscopy that we are exploring in a number of application ranging from cell tracking to sensitive detection of molecular targets and cancer cells in vivo.
1) Sokolov KV, Follen M, Aaron J, Pavlova I, Malpica A, Lotan R, Richards-Kortum R. Real-Time Vital Optical Imaging of Precancer Using Anti-Epidermal Growth Factor Receptor Antibodies Conjugated to Gold Nanoparticles. Cancer Res 63:1999-2004, 2003.