In Vivo Imaging of Nanoparticle Delivery and Tumor Microvasculature with Multimodal Optical Coherence Tomography References and Links

Current imaging techniques capable of tracking nanoparticles in vivo supply either a large field of view or cellular resolution, but not both. Here, we demonstrate a multimodality imaging platform of optical coherence tomography (OCT) techniques for high resolution, wide field of view in vivo imaging of nanoparticles. This platform includes the first in vivo images of nanoparticle pharmacokinetics acquired with photothermal OCT (PTOCT), along with overlaying images of microvascular and tissue morphology. Gold nanorods (51.8 ± 8.1 nm by 15.2 ± 3.3 nm) were intravenously injected into mice, and their accumulation into mammary tumors was non-invasively imaged in vivo in three dimensions over 24 hours using PTOCT. Spatial frequency analysis of PTOCT images indicated that gold nanorods reached peak distribution throughout the tumors by 16 hours, and remained well-dispersed up to 24 hours post-injection. In contrast, the overall accumulation of gold nanorods within the tumors peaked around 16 hours post-injection. The accumulation of gold nanorods within the tumors was validated post-mortem with multiphoton microscopy. This shows the utility of PTOCT as part of a powerful multimodality imaging platform for the development of nanomedicines and drug delivery technologies.

Craig L Duvall | Melissa C Skala | N. K. Agrawal | Amy T Shah | Jason M Tucker-Schwartz | J. Duker | J. Schuman | M. Dewhirst | N. Yuldasheva | J. Izatt | N. Munce | I. Vitkin | M. Bawendi | C. Puliafito | S. Emelianov | S. Boppart | A. Oldenburg | I. Gorczynska | A. Schwartz | W. Stinson | M. Hee | K. Gregory | K. Homan | V. Torchilin | N. Halas | R. Drezek | J. Haldar | C. Duvall | A. Cable | B. Bouma | S. Adie | T. Bajraszewski | J. Frangioni | R. Kuranov | C. Michelich | G. Tearney | Q. Yin-Goen | P. Targowski | A. Kowalczyk | P. Kruizinga | J. Tyrrell | M. Villiger | T. Lasser | C. Santschi | T. Niidome | B. Standish | E. Moriyama | T. Ralston | T. Sau | S. Ashkenazi | C. Orendorff | B. Korgel | H. Ghandehari | Kelsey R. Beavers | Arnida | D. Slatkin | H. Smilowitz | T. M. Focella | M. Napier | T. Larson | W. Hagens | R. Geertsma | J. Tunnell | C. Walkey | A. Byrnes | C. Landon | A. Bouwens | M. Skala | A. Shah | J. Goulley | B. Applegate | R. Rezaeipoor | N. Bocchio | S. Krishnan | Kelsey R Beavers | Wesley W Sit | J. Tucker-Schwartz | K. Day | M. Janat-Amsbury | J. Fang | G. Paciotti | T. Mori | Silica | S. Kim | T. Flotte | M. Day | T. L. T. ten Hagen | L. Ma | M. Marjanovic | E. Swanson | J. DeSimone | A. Ray | D. M. Shin | W. L. Monsky | D. Halaney | R. Shelton | L. Tamarkin | J. W. Villard | J. de Boer | M. C. Burger | S. E. Hunyadi | W. Sit | C. Berclaz | A. J. Simnick | D. Fukumura | Fujimoto | J. Fujimoto | J. Jiang | A Mariampillai | M. K. Leung | B. Wilson | V. X. Yang | M. Khurana | R. Wang | Z. Chen | Wojtkowski | T. Ko | Vakoc | M. Natan | J. E. Bear | K. R. Beavers | P. Krystek | C. A. Patil | J. Liu | A. J. Lin | S. W. Huang | J M Tucker-Schwartz | T. A. Meyer | Y Jung | R. Reif | Y. Zeng | T. Hong | D. C. Colvin | Y. Xu | A. K. Dunn | C Pache | W. Lee | R. Jain | W. Chan | M. El-Sayed | A. Park | Guan | Z. Huang | S D Perrault | T. Jennings | H. C. Fischer | J. Cheng | Y Akiyama | Y. Katayama | C. M. Peterson | R. A. Roberts | G. R. Robbins | J. Perry | M. P. Kai | K. Chen | T. Bo | D. Huang | J. P. Zimmer | A. J. Sips | T. Li | Jones | C. Joo | H C Hendargo | Wang | S. Gambhir | S. Chen | C. P. Lin | W. Chang | B. Tromberg | A M Gobin | M. H. Lee | W. D. James | J. L. West | J F Hainfeld | Anisotropic | H. Nakamura | I. El-Sayed | Nie | A. Estrada | Milner | W. Liu | R. Lanning | T. Padera | L. Bartlett | T. Stylianopoulos | L. Munn | A. Chilkoti | X. Huang | J. Schwartz | W. Park | R. E. Shetty | R. J. Price | J. C. Stafford | K. Uthamanthil | R. J. Pham | C. L. Mcnichols | J. D. Coleman | F P Payne | J. G. H. Von Maltzahn | S. K. Bandaru | M. J. Das | S. Sailor | Bhatia | S K Libutti | H. R. Alexander | W. E. Gannon | M. Walker | G. D. Seidel | A Agarwal | M. O 'donnell | N. Kotov | A K Oyelere | P. Chen | N J Durr | D. Smith | K. Sokolov | A. Ben-Yakar | J Park | P. Diagaradjane | Intra-Organ | X M Qian | X. Peng | D. O. Ansari | G. Z. Chen | L. Yang | A. N. Young | S. Wang | W H De Jong | W. Frey | C L Zavaleta | B. R. Smith | I. Walton | W. Doering | G. Davis | B. Shojaei | L Tong | Q. Wei | A. Wei | Gold | J Fang | H. Maeda | R John | E. J. Chaney | B. P. Sutton | D Jacob | A L Oldenburg | M. N. Hansen | S. C. Adler | R. Huang | J. Huber | A S Paranjape | S. Baranov | T. Wang | K. P. Feldman | T. E. Johnston | S K Hobbs | F. Yuan | W. G. Roberts | L. Griffith | H S Choi | P. Misra | E. Tanaka | B. Itty Ipe | Renal | A K Iyer | G. Khaled | C J Murphy | A. M. Gole | J. Gao | L. Gou | T Akkin | R. Estrada | S. J. Chiu | C. Tomasi | S. Farsiu | M R Dreher | D. Ho | T. E. Feldman | A A Manzoor | L. H. Lindner | J. Y. Park | M. R. Dreher | S. Das | G. Hanna | G. A. Koning | D. Needham | Overcoming | H M Subhash | H. Xie | J. W. Smith | O. J. T. Mccarty | J. Ting | M. Gibson

[1]  Ji-Xin Cheng,et al.  Gold Nanorods as Contrast Agents for Biological Imaging: Optical Properties, Surface Conjugation and Photothermal Effects † , 2009, Photochemistry and photobiology.

[2]  Benjamin J Vakoc,et al.  Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging , 2009, Nature Medicine.

[3]  Lawrence Tamarkin,et al.  Phase I and Pharmacokinetic Studies of CYT-6091, a Novel PEGylated Colloidal Gold-rhTNF Nanomedicine , 2010, Clinical Cancer Research.

[4]  Ruikang K. Wang,et al.  Three-dimensional high-resolution imaging of gold nanorods uptake in sentinel lymph nodes. , 2011, Nano letters.

[5]  David L. Halaney,et al.  Two-photon luminescence properties of gold nanorods , 2013, Biomedical optics express.

[6]  Melissa C Skala,et al.  Dual-modality photothermal optical coherence tomography and magnetic-resonance imaging of carbon nanotubes. , 2012, Optics letters.

[7]  J. Fujimoto Optical coherence tomography for ultrahigh resolution in vivo imaging , 2003, Nature Biotechnology.

[8]  J. Fujimoto,et al.  Photothermal detection of gold nanoparticles using phase-sensitive optical coherence tomography. , 2008, Optics express.

[9]  J. West,et al.  Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy. , 2007, Nano letters.

[10]  S. Emelianov,et al.  Silica-coated gold nanorods as photoacoustic signal nanoamplifiers. , 2011, Nano letters.

[11]  Michael J Sailor,et al.  Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas. , 2009, Cancer research.

[12]  Sucbei Moon,et al.  Reference spectrum extraction and fixed-pattern noise removal in optical coherence tomography , 2010, Optics express.

[13]  Carlo Tomasi,et al.  Automated non-rigid registration and mosaicing for robust imaging of distinct retinal capillary beds using speckle variance optical coherence tomography , 2013, Biomedical optics express.

[14]  Sheng-Wen Huang,et al.  Targeted gold nanorod contrast agent for prostate cancer detection by photoacoustic imaging , 2007 .

[15]  M. Dewhirst,et al.  Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers. , 2006, Journal of the National Cancer Institute.

[16]  J. Duker,et al.  Ultrahigh Speed, Ultrahigh Resolution Optical Coherence Tomography Using Spectral Domain Detection , 2004 .

[17]  Sanjiv S. Gambhir,et al.  Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy , 2009, Proceedings of the National Academy of Sciences.

[18]  Warren C W Chan,et al.  Mediating tumor targeting efficiency of nanoparticles through design. , 2009, Nano letters.

[19]  Xiaohua Huang,et al.  Peptide-conjugated gold nanorods for nuclear targeting. , 2007, Bioconjugate chemistry.

[20]  H. Maeda,et al.  Exploiting the enhanced permeability and retention effect for tumor targeting. , 2006, Drug discovery today.

[21]  G. Ripandelli,et al.  Optical coherence tomography. , 1998, Seminars in ophthalmology.

[22]  Ruikang K. Wang,et al.  Depth profiling of photothermal compound concentrations using phase sensitive optical coherence tomography. , 2011, Journal of biomedical optics.

[23]  Travis A. Meyer,et al.  In vivo photothermal optical coherence tomography of gold nanorod contrast agents , 2012, Biomedical optics express.

[24]  Petra Krystek,et al.  Particle size-dependent organ distribution of gold nanoparticles after intravenous administration. , 2008, Biomaterials.

[25]  R. Jain,et al.  Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Bruce J. Tromberg,et al.  A comparison of Doppler optical coherence tomography methods , 2012, Biomedical optics express.

[27]  R. John,et al.  In vivo magnetomotive optical molecular imaging using targeted magnetic nanoprobes , 2010, Proceedings of the National Academy of Sciences.

[28]  M. Dewhirst,et al.  Overcoming limitations in nanoparticle drug delivery: triggered, intravascular release to improve drug penetration into tumors. , 2012, Cancer research.

[29]  J F Hainfeld,et al.  Gold nanoparticles: a new X-ray contrast agent. , 2006, The British journal of radiology.

[30]  M. Bawendi,et al.  Renal clearance of quantum dots , 2007, Nature Biotechnology.

[31]  May D. Wang,et al.  In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags , 2008, Nature Biotechnology.

[32]  S. Gambhir,et al.  Gold nanoparticles: a revival in precious metal administration to patients. , 2011, Nano letters.

[33]  James E Bear,et al.  Nanoparticle clearance is governed by Th1/Th2 immunity and strain background. , 2013, The Journal of clinical investigation.

[34]  Jun Fang,et al.  The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. , 2011, Advanced drug delivery reviews.

[35]  Jeffrey W. Smith,et al.  Optical detection of indocyanine green encapsulated biocompatible poly (lactic-co-glycolic) acid nanoparticles with photothermal optical coherence tomography. , 2012, Optics letters.

[36]  Ryan L. Shelton,et al.  Fourier domain pump-probe optical coherence tomography imaging of Melanin , 2009, 2009 Conference on Lasers and Electro-Optics and 2009 Conference on Quantum electronics and Laser Science Conference.

[37]  C. Murphy,et al.  Anisotropic metal nanoparticles: Synthesis, assembly, and optical applications. , 2005, The journal of physical chemistry. B.

[38]  Adrian Mariampillai,et al.  Speckle variance detection of microvasculature using swept-source optical coherence tomography. , 2008, Optics letters.

[39]  Theo Lasser,et al.  Fast Three-dimensional Imaging of Gold Nanoparticles in Living Cells with Photothermal Optical Lock-in Optical Coherence Microscopy , 2022 .

[40]  Taner Akkin,et al.  Depth-resolved measurement of transient structural changes during action potential propagation. , 2007, Biophysical journal.

[41]  Melissa C Skala,et al.  Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres. , 2008, Nano letters.

[42]  Amit S. Paranjape,et al.  Depth resolved photothermal OCT detection of macrophages in tissue using nanorose , 2010, Biomedical optics express.

[43]  R Jason Stafford,et al.  Feasibility study of particle-assisted laser ablation of brain tumors in orthotopic canine model. , 2009, Cancer research.

[44]  A. Dunn,et al.  Intra‐organ biodistribution of gold nanoparticles using intrinsic two‐photon‐induced photoluminescence , 2010, Lasers in surgery and medicine.

[45]  Hamidreza Ghandehari,et al.  Geometry and surface characteristics of gold nanoparticles influence their biodistribution and uptake by macrophages. , 2011, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[46]  K. Sokolov,et al.  Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods. , 2007, Nano letters.

[47]  Amy L Oldenburg,et al.  Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography. , 2009, Journal of materials chemistry.

[48]  T. Niidome,et al.  The effects of PEG grafting level and injection dose on gold nanorod biodistribution in the tumor-bearing mice. , 2009, Journal of controlled release : official journal of the Controlled Release Society.