BACKGROUND AND OBJECTIVES: Gold nanoparticles (GNPs) such as gold nanoshells (GNSs) and gold nanorods (GNRs) have been explored in a number of in vitro and in vivo studies as imaging contrast and cancer therapy agents due to their highly desirable spectral and molecular properties. While the organ-level biodistribution of these particles has been reported previously, little is known about the cellular level or intra-organ biodistribution. The objective of this study was to demonstrate the use of intrinsic two-photon induced photoluminescence (TPIP) to study the cellular level biodistribution of GNPs. STUDY DESIGN/ MATERIALS AND METHODS: Tumor xenografts were created in twenty-seven male nude mice (Swiss nu/nu) using HCT 116 cells (CCL-247, ATCC, human colorectal cancer cell line). GNSs and GNRs were systemically injected 24 hr. prior to tumor harvesting. A skin flap with the tumor was excised and sectioned as 8 μm thick tissues for imaging GNPs under a custom-built multiphoton microscope. For multiplexed imaging, nuclei, cytoplasm, and blood vessels were demonstrated by hematoxylin and eosin (H&E) staining, YOYO-1 iodide staining and CD31-immunofluorescence staining. RESULTS: Distribution features of GNPs at the tumor site were determined from TPIP images. GNSs and GNRs had a heterogeneous distribution with higher accumulation at the tumor cortex than tumor core. GNPs were also observed in unique patterns surrounding the perivascular region. While most GNSs were confined at the distance of approximately 400 μm inside the tumor edge, GNRs were shown up to 1.5 mm penetration inside the edge. CONCLUSIONS: We have demonstrated the use of TPIP imaging in a multiplexed fashion to image both GNPs and nuclei, cytoplasm, or vasculature simultaneously. We also confirmed that TPIP imaging enabled visualization of GNP distribution patterns within the tumor and other critical organs. These results suggest that direct luminescence-based imaging of metal nanoparticles holds a valuable and promising position in understanding the accumulation kinetics of GNPs. In addition, these techniques will be increasingly important as the use of these particles progress to human clinical trials where standard histopathology techniques are used to analyze their effects.
BACKGROUND AND OBJECTIVES: Gold nanoparticles (GNPs) such as gold nanoshells (GNSs) and gold nanorods (GNRs) have been explored in a number of in vitro and in vivo studies as imaging contrast and cancer therapy agents due to their highly desirable spectral and molecular properties. While the organ-level biodistribution of these particles has been reported previously, little is known about the cellular level or intra-organ biodistribution. The objective of this study was to demonstrate the use of intrinsic two-photon induced photoluminescence (TPIP) to study the cellular level biodistribution of GNPs. STUDY DESIGN/ MATERIALS AND METHODS:Tumor xenografts were created in twenty-seven male nude mice (Swiss nu/nu) using HCT 116 cells (CCL-247, ATCC, humancolorectal cancer cell line). GNSs and GNRs were systemically injected 24 hr. prior to tumor harvesting. A skin flap with the tumor was excised and sectioned as 8 μm thick tissues for imaging GNPs under a custom-built multiphoton microscope. For multiplexed imaging, nuclei, cytoplasm, and blood vessels were demonstrated by hematoxylin and eosin (H&E) staining, YOYO-1 iodide staining and CD31-immunofluorescence staining. RESULTS: Distribution features of GNPs at the tumor site were determined from TPIP images. GNSs and GNRs had a heterogeneous distribution with higher accumulation at the tumor cortex than tumor core. GNPs were also observed in unique patterns surrounding the perivascular region. While most GNSs were confined at the distance of approximately 400 μm inside the tumor edge, GNRs were shown up to 1.5 mm penetration inside the edge. CONCLUSIONS: We have demonstrated the use of TPIP imaging in a multiplexed fashion to image both GNPs and nuclei, cytoplasm, or vasculature simultaneously. We also confirmed that TPIP imaging enabled visualization of GNP distribution patterns within the tumor and other critical organs. These results suggest that direct luminescence-based imaging of metal nanoparticles holds a valuable and promising position in understanding the accumulation kinetics of GNPs. In addition, these techniques will be increasingly important as the use of these particles progress to human clinical trials where standard histopathology techniques are used to analyze their effects.
Authors: Warren R Zipfel; Rebecca M Williams; Richard Christie; Alexander Yu Nikitin; Bradley T Hyman; Watt W Webb Journal: Proc Natl Acad Sci U S A Date: 2003-05-19 Impact factor: 11.205
Authors: Haifeng Wang; Terry B Huff; Daniel A Zweifel; Wei He; Philip S Low; Alexander Wei; Ji-Xin Cheng Journal: Proc Natl Acad Sci U S A Date: 2005-10-20 Impact factor: 11.205
Authors: Priyaveena Puvanakrishnan; Jaesook Park; Parmeswaran Diagaradjane; Jon A Schwartz; Chris L Coleman; Kelly L Gill-Sharp; Kristina L Sang; J Donald Payne; Sunil Krishnan; James W Tunnell Journal: J Biomed Opt Date: 2009 Mar-Apr Impact factor: 3.170
Authors: Meng-Lin Li; James Chunjay Wang; Jon A Schwartz; Kelly L Gill-Sharp; George Stoica; Lihong V Wang Journal: J Biomed Opt Date: 2009 Jan-Feb Impact factor: 3.170
Authors: Andrew J Coughlin; Jeyarama S Ananta; Nanfu Deng; Irina V Larina; Paolo Decuzzi; Jennifer L West Journal: Small Date: 2013-09-23 Impact factor: 13.281
Authors: R Jason Stafford; Anil Shetty; Andrew M Elliott; Jon A Schwartz; Glenn P Goodrich; John D Hazle Journal: Int J Hyperthermia Date: 2011 Impact factor: 3.914
Authors: Jason M Tucker-Schwartz; Kelsey R Beavers; Wesley W Sit; Amy T Shah; Craig L Duvall; Melissa C Skala Journal: Biomed Opt Express Date: 2014-05-01 Impact factor: 3.732