Image-guided tumor surgery: will there be a role for fluorescent nanoparticles?

Image-guided surgery (IGS) using fluorescent nanoparticles (NPs) has the potential to substantially impact patient treatment. The use of fluorescence imaging provides surgeons with real-time feedback on the location of diseased tissue using safe, low-cost imaging agents and instrumentation. Fluorescent NPs are likely to play a role as they are capable of taking advantage of the enhanced permeability and retention (EPR) effect and can be modified to avoid clearance, increase circulation time, and specifically target tumors. Clinical trials of IGS using the FDA-approved fluorophores indocyanine green and methylene blue have already shown preliminary successes, and incorporation of fluorescent NPs will likely improve detection by providing higher signal to background ratio and reducing false-positive rates through active targeting. Preclinical development of fluorescent NP formulations is advancing rapidly, with strategies ranging from passive targeting to active targeting of cell surface receptors, creating pH-responsive NPs, and increasing cell uptake through cleavable proteins. This collective effort could lead to clinical trials using fluorescent NPs in the near future. WIREs Nanomed Nanobiotechnol 2016, 8:498-511. doi: 10.1002/wnan.1381 For further resources related to this article, please visit the WIREs website.

[1]  M. Kattan,et al.  Location, extent and number of positive surgical margins do not improve accuracy of predicting prostate cancer recurrence after radical prostatectomy. , 2009, The Journal of urology.

[2]  Xiaoyang Xu,et al.  Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. , 2014, Advanced drug delivery reviews.

[3]  P. Low,et al.  Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results , 2011, Nature Medicine.

[4]  Ralph Weissleder,et al.  Near-infrared fluorescence: application to in vivo molecular imaging. , 2010, Current opinion in chemical biology.

[5]  L. Ellis,et al.  Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  Osamu Ishikawa,et al.  A novel image‐guided surgery of hepatocellular carcinoma by indocyanine green fluorescence imaging navigation , 2009, Journal of surgical oncology.

[7]  Ralph Weissleder,et al.  A multimodal nanoparticle for preoperative magnetic resonance imaging and intraoperative optical brain tumor delineation. , 2003, Cancer research.

[8]  B. Guillonneau,et al.  Positive surgical margins in radical prostatectomy: outlining the problem and its long-term consequences. , 2009, European urology.

[9]  M. Uesaka,et al.  Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. , 2011, Nature nanotechnology.

[10]  Takayuki Kinoshita,et al.  Evaluation of sentinel node biopsy by combined fluorescent and dye method and lymph flow for breast cancer. , 2010, Breast.

[11]  C. V. D. van de Velde,et al.  Real-time intraoperative detection of breast cancer using near-infrared fluorescence imaging and Methylene Blue. , 2014, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[12]  A. Vahrmeijer,et al.  Image-guided cancer surgery using near-infrared fluorescence , 2013, Nature Reviews Clinical Oncology.

[13]  Chad A. Mirkin,et al.  Nanotechnology-Based Precision Tools for the Detection and Treatment of Cancer. , 2015, Anticancer research.

[14]  J. Frangioni,et al.  Effective Low-dose Escalation of Indocyanine Green for Near-infrared Fluorescent Sentinel Lymph Node Mapping in Melanoma , 2013, Annals of Surgical Oncology.

[15]  Merrick I Ross,et al.  Positive surgical margins and ipsilateral breast tumor recurrence predict disease‐specific survival after breast‐conserving therapy , 2003, Cancer.

[16]  T. Mihaljevic,et al.  Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping , 2004, Nature Biotechnology.

[17]  R. Tsien,et al.  Activatable cell penetrating peptides linked to nanoparticles as dual probes for in vivo fluorescence and MR imaging of proteases , 2010, Proceedings of the National Academy of Sciences.

[18]  Seiya Inoue,et al.  Sentinel Lymph Node Biopsy Using Intraoperative Indocyanine Green Fluorescence Imaging Navigated with Preoperative CT Lymphography for Superficial Esophageal Cancer , 2012, Annals of Surgical Oncology.

[19]  M. Frenz,et al.  Indocyanine green loaded biocompatible nanoparticles: Stabilization of indocyanine green (ICG) using biocompatible silica-poly(ε-caprolactone) grafted nanocomposites , 2013 .

[20]  Xiaohua Huang,et al.  Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. , 2006, Journal of the American Chemical Society.

[21]  B. Chung,et al.  Indocyanine green encapsulated nanogels for hyaluronidase activatable and selective near infrared imaging of tumors and lymph nodes. , 2012, Chemical communications.

[22]  Jerry S. H. Lee,et al.  Magnetic nanoparticles in MR imaging and drug delivery. , 2008, Advanced drug delivery reviews.

[23]  P. Choyke,et al.  Near infrared fluorescence‐guided real‐time endoscopic detection of peritoneal ovarian cancer nodules using intravenously injected indocyanine green , 2011, International journal of cancer.

[24]  Shuming Nie,et al.  Intraoperative Near-Infrared Imaging Can Distinguish Cancer from Normal Tissue but Not Inflammation , 2014, PloS one.

[25]  A. Jemal,et al.  Cancer treatment and survivorship statistics, 2014 , 2014, CA: a cancer journal for clinicians.

[26]  Patrick Couvreur,et al.  Design, Functionalization Strategies and Biomedical Applications of Targeted Biodegradable/Biocompatible Polymer‐Based Nanocarriers for Drug Delivery , 2013 .

[27]  N. Gusani,et al.  Survival Outcomes of Patients with Colorectal Liver Metastases Following Hepatic Resection or Ablation in the Era of Effective Chemotherapy , 2009, Annals of Surgical Oncology.

[28]  Xiaogang Liu,et al.  Upconversion multicolor fine-tuning: visible to near-infrared emission from lanthanide-doped NaYF4 nanoparticles. , 2008, Journal of the American Chemical Society.

[29]  Evelyne M. Loyer,et al.  Effect of Surgical Margin Status on Survival and Site of Recurrence After Hepatic Resection for Colorectal Metastases , 2005, Annals of surgery.

[30]  A. Mohs,et al.  Indocyanine green-loaded nanoparticles for image-guided tumor surgery. , 2015, Bioconjugate chemistry.

[31]  R. Tsien,et al.  Therapeutics , Targets , and Chemical Biology Real-time In Vivo Molecular Detection of Primary Tumors and Metastases with Ratiometric Activatable Cell-Penetrating Peptides , 2013 .

[32]  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.

[33]  A. Judge,et al.  Hypersensitivity and loss of disease site targeting caused by antibody responses to PEGylated liposomes. , 2006, Molecular therapy : the journal of the American Society of Gene Therapy.

[34]  Shuming Nie,et al.  An Integrated Widefield Imaging and Spectroscopy System for Contrast-Enhanced, Image-Guided Resection of Tumors , 2015, IEEE Transactions on Biomedical Engineering.

[35]  K. Kang,et al.  Near infrared dye indocyanine green doped silica nanoparticles for biological imaging. , 2012, Talanta.

[36]  Miriam Scadeng,et al.  Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival , 2010, Proceedings of the National Academy of Sciences.

[37]  E. Sevick-Muraca,et al.  Quantitative optical spectroscopy for tissue diagnosis. , 1996, Annual review of physical chemistry.

[38]  Vladimir P. Torchilin,et al.  Immunomicelles: Targeted pharmaceutical carriers for poorly soluble drugs , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[39]  Merlijn Hutteman,et al.  The clinical use of indocyanine green as a near‐infrared fluorescent contrast agent for image‐guided oncologic surgery , 2011, Journal of surgical oncology.

[40]  V. Ntziachristos,et al.  Monoclonal antibody-targeted PEGylated liposome-ICG encapsulating doxorubicin as a potential theranostic agent. , 2015, International journal of pharmaceutics.

[41]  John V. Frangioni,et al.  The Value of Intraoperative Near-Infrared Fluorescence Imaging Based on Enhanced Permeability and Retention of Indocyanine Green: Feasibility and False-Positives in Ovarian Cancer , 2015, PloS one.

[42]  H. Dai,et al.  Ultrasmall reduced graphene oxide with high near-infrared absorbance for photothermal therapy. , 2011, Journal of the American Chemical Society.

[43]  Kevin J. Kauffman,et al.  Cancer nanotherapeutics in clinical trials. , 2015, Cancer treatment and research.

[44]  Baran D. Sumer,et al.  Ultra-pH-Sensitive Nanoprobe Library with Broad pH Tunability and Fluorescence Emissions , 2014, Journal of the American Chemical Society.

[45]  Jason M Warram,et al.  The status of contemporary image-guided modalities in oncologic surgery. , 2015, Annals of surgery.

[46]  John V Frangioni,et al.  New technologies for human cancer imaging. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[47]  Leonora S F Boogerd,et al.  Real-time near-infrared fluorescence guided surgery in gynecologic oncology: a review of the current state of the art. , 2014, Gynecologic oncology.

[48]  John V Frangioni,et al.  Intraoperative sentinel lymph node mapping of the lung using near-infrared fluorescent quantum dots. , 2005, The Annals of thoracic surgery.

[49]  Aniruddha Roy,et al.  Factors controlling the pharmacokinetics, biodistribution and intratumoral penetration of nanoparticles. , 2013, Journal of controlled release : official journal of the Controlled Release Society.

[50]  Beom Suk Lee,et al.  Theranostic nanoparticles based on PEGylated hyaluronic acid for the diagnosis, therapy and monitoring of colon cancer. , 2012, Biomaterials.

[51]  Vishal Saxena,et al.  Polymeric nanoparticulate delivery system for Indocyanine green: biodistribution in healthy mice. , 2006, International journal of pharmaceutics.

[52]  Hak Soo Choi,et al.  Image-Guided Oncologic Surgery Using Invisible Light: Completed Pre-Clinical Development for Sentinel Lymph Node Mapping , 2006, Annals of Surgical Oncology.

[53]  S. Orsulic,et al.  Mouse models of cancer. , 2011, Annual review of pathology.

[54]  Dennis E Discher,et al.  Minimal " Self " Peptides That Inhibit Phagocytic Clearance and Enhance Delivery of Nanoparticles References and Notes , 2022 .

[55]  Sylvain Gioux,et al.  Real-time intra-operative near-infrared fluorescence identification of the extrahepatic bile ducts using clinically available contrast agents. , 2010, Surgery.

[56]  E. Scott,et al.  Gadolinium-doped silica nanoparticles encapsulating indocyanine green for near infrared and magnetic resonance imaging. , 2012, Small.

[57]  A. Fernández-Medarde,et al.  Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy. , 2015, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[58]  Nicholas A Peppas,et al.  Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. , 2006, International journal of pharmaceutics.

[59]  Baran D. Sumer,et al.  A Broad Nanoparticle-Based Strategy for Tumor Imaging by Nonlinear Amplification of Microenvironment Signals , 2013, Nature materials.

[60]  Kenneth Hess,et al.  Recurrence and Outcomes Following Hepatic Resection, Radiofrequency Ablation, and Combined Resection/Ablation for Colorectal Liver Metastases , 2004, Annals of surgery.

[61]  Rudolf Zentel,et al.  Overcoming the PEG-addiction: well-defined alternatives to PEG, from structure–property relationships to better defined therapeutics , 2011 .

[62]  Shuming Nie,et al.  Nanotechnology applications in surgical oncology. , 2010, Annual review of medicine.

[63]  J. Joo,et al.  Comparison of Sentinel Lymph Node Biopsy Guided by the Multimodal Method of Indocyanine Green Fluorescence, Radioisotope, and Blue Dye Versus the Radioisotope Method in Breast Cancer: A Randomized Controlled Trial , 2014, Annals of Surgical Oncology.

[64]  May D. Wang,et al.  Hand-held spectroscopic device for in vivo and intraoperative tumor detection: contrast enhancement, detection sensitivity, and tissue penetration. , 2010, Analytical chemistry.

[65]  W. Fawcett,et al.  Survival and recurrence after neo-adjuvant chemotherapy and liver resection for colorectal metastases: a ten year study. , 2009, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[66]  F. Zanella,et al.  Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. , 2006, The Lancet. Oncology.

[67]  Samuel Achilefu,et al.  Hands-free, wireless goggles for near-infrared fluorescence and real-time image-guided surgery. , 2011, Surgery.

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

[69]  Robert Langer,et al.  Nanoparticle delivery of cancer drugs. , 2012, Annual review of medicine.

[70]  Stephen J. Lomnes,et al.  Tissue-like phantoms for near-infrared fluorescence imaging system assessment and the training of surgeons. , 2006, Journal of biomedical optics.

[71]  F M Muggia,et al.  Complement activation following first exposure to pegylated liposomal doxorubicin (Doxil): possible role in hypersensitivity reactions. , 2003, Annals of oncology : official journal of the European Society for Medical Oncology.

[72]  Vladimir Torchilin,et al.  Tumor delivery of macromolecular drugs based on the EPR effect. , 2011, Advanced drug delivery reviews.

[73]  Jie Tian,et al.  Use of Indocyanine Green for Detecting the Sentinel Lymph Node in Breast Cancer Patients: From Preclinical Evaluation to Clinical Validation , 2013, PloS one.

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

[75]  J. Frangioni,et al.  Image-Guided Surgery Using Invisible Near-Infrared Light: Fundamentals of Clinical Translation , 2010, Molecular imaging.

[76]  M. Ferrari Cancer nanotechnology: opportunities and challenges , 2005, Nature Reviews Cancer.

[77]  Mark E. Davis,et al.  Nanoparticle therapeutics: an emerging treatment modality for cancer , 2008, Nature Reviews Drug Discovery.

[78]  Kwangmeyung Kim,et al.  PEGylation of hyaluronic acid nanoparticles improves tumor targetability in vivo. , 2011, Biomaterials.

[79]  Sylvain Gioux,et al.  The FLARE Intraoperative Near-Infrared Fluorescence Imaging System: A First-in-Human Clinical Trial in Perforator Flap Breast Reconstruction , 2010, Plastic and reconstructive surgery.

[80]  C. Geyer,et al.  Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in five National Surgical Adjuvant Breast and Bowel Project node-positive adjuvant breast cancer trials. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[81]  Kwangmeyung Kim,et al.  Smart nanocarrier based on PEGylated hyaluronic acid for cancer therapy. , 2011, ACS nano.

[82]  Sylvain Gioux,et al.  High-Power, Computer-Controlled, Light-Emitting Diode–Based Light Sources for Fluorescence Imaging and Image-Guided Surgery , 2009, Molecular imaging.

[83]  Z. Dai,et al.  Indocyanine green loaded SPIO nanoparticles with phospholipid-PEG coating for dual-modal imaging and photothermal therapy. , 2013, Biomaterials.

[84]  Leaf Huang,et al.  Stealth nanoparticles: high density but sheddable PEG is a key for tumor targeting. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[85]  R. Deberardinis,et al.  A nanoparticle-based strategy for the imaging of a broad range of tumours by nonlinear amplification of microenvironment signals , 2013 .

[86]  C. V. D. van de Velde,et al.  Near-infrared fluorescence imaging of a solitary fibrous tumor of the pancreas using methylene blue. , 2012, World Journal of Gastrointestinal Surgery.

[87]  V. Torchilin,et al.  Immunoconjugates and long circulating systems: origins, current state of the art and future directions. , 2013, Advanced drug delivery reviews.

[88]  Bahman Anvari,et al.  Biodistribution of encapsulated indocyanine green in healthy mice. , 2009, Molecular pharmaceutics.

[89]  Paul Steinbach,et al.  Real-time in vivo molecular detection of primary tumors and metastases with ratiometric activatable cell-penetrating peptides. , 2013, Cancer research.

[90]  Michael J Sailor,et al.  Biodegradable luminescent porous silicon nanoparticles for in vivo applications. , 2009, Nature materials.

[91]  Jiao Chen,et al.  Upconversion Nanomaterials: Synthesis, Mechanism, and Applications in Sensing , 2012, Sensors.

[92]  P. Couvreur,et al.  Nanoparticles in cancer therapy and diagnosis. , 2002, Advanced drug delivery reviews.

[93]  M. Kattan,et al.  Prognostic impact of positive surgical margins in surgically treated prostate cancer: multi-institutional assessment of 5831 patients. , 2005, Urology.

[94]  R. Pleijhuis,et al.  Obtaining Adequate Surgical Margins in Breast-Conserving Therapy for Patients with Early-Stage Breast Cancer: Current Modalities and Future Directions , 2009, Annals of Surgical Oncology.

[95]  H. Maeda The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. , 2001, Advances in enzyme regulation.

[96]  Pedro M. Valencia,et al.  Targeted Polymeric Therapeutic Nanoparticles: Design, Development and Clinical Translation , 2012 .